The scenario describes a patient with a known history of atrial fibrillation presenting with acute neurological deficits consistent with an ischemic stroke. The core of the question lies in understanding the optimal initial management strategy for such a patient, specifically concerning reperfusion therapy. Given the patient’s presentation within the therapeutic window for intravenous thrombolysis (IVT) and the absence of contraindications, IV alteplase is the first-line treatment. The rationale for this choice is based on established guidelines for acute ischemic stroke management, which prioritize rapid reperfusion to salvage ischemic penumbra and improve functional outcomes. While mechanical thrombectomy is a crucial intervention for eligible patients, it is typically considered in conjunction with or as an alternative to IVT, particularly for large vessel occlusions, and often requires confirmation of the occlusion via advanced imaging. The question probes the understanding of the sequential and evidence-based approach to acute stroke care. The correct approach involves immediate administration of IV alteplase if criteria are met, followed by further assessment for potential mechanical thrombectomy if indicated. The other options represent either delayed or inappropriate interventions given the clinical context. For instance, initiating anticoagulation without prior reperfusion therapy in the acute phase of ischemic stroke is generally not recommended due to the risk of hemorrhagic transformation. Similarly, delaying reperfusion therapy to await advanced imaging without considering the time-sensitive nature of stroke treatment would be detrimental. The emphasis on rapid assessment and intervention aligns with the core principles of vascular neurology as taught at the American Board of Psychiatry and Neurology – Subspecialty in Vascular Neurology University, highlighting the critical role of timely reperfusion in maximizing neurological recovery.

The question probes the understanding of neuroinflammatory mechanisms in the context of acute ischemic stroke and the potential therapeutic implications of modulating specific immune cell populations. In acute ischemic stroke, reperfusion injury is a significant contributor to secondary brain damage. This process involves a complex interplay of cellular and molecular events, including the activation of microglia and astrocytes, infiltration of peripheral immune cells such as neutrophils and monocytes/macrophages, and the release of pro-inflammatory cytokines. Microglia, the resident immune cells of the central nervous system, are rapidly activated upon ischemic insult. Initially, they can adopt a neuroprotective phenotype, clearing debris and releasing trophic factors. However, with prolonged or severe ischemia, they often transition to a pro-inflammatory state, releasing cytotoxic mediators like reactive oxygen species (ROS), nitric oxide (NO), and pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). These mediators can exacerbate neuronal damage and contribute to the expansion of the infarct core. Neutrophils and monocytes/macrophages also infiltrate the ischemic penumbra and infarct core. Neutrophils are among the first peripheral immune cells to arrive, releasing proteases and inflammatory cytokines that can damage the blood-brain barrier (BBB) and contribute to microvascular dysfunction. Monocytes differentiate into macrophages within the brain tissue, and their phenotype can be diverse, with some promoting inflammation and others aiding in debris clearance and tissue repair. The blood-brain barrier (BBB) integrity is compromised during ischemia and reperfusion. This breakdown allows for the extravasation of plasma proteins and peripheral immune cells into the brain parenchyma, further fueling the inflammatory cascade. The inflammatory response, while initially intended to clear damaged tissue, can become detrimental if dysregulated, leading to bystander damage to viable neurons in the penumbra. Therefore, targeting the inflammatory cascade by modulating the activity of these immune cells, particularly by dampening the pro-inflammatory responses of activated microglia and infiltrating neutrophils, represents a promising therapeutic strategy. Strategies aimed at reducing the release of inflammatory mediators or promoting a shift towards a more anti-inflammatory or reparative phenotype in immune cells could potentially limit infarct expansion and improve functional outcomes.

The question probes the understanding of the interplay between cerebral autoregulation and the efficacy of thrombolytic therapy in acute ischemic stroke, specifically concerning the impact of impaired autoregulation on reperfusion. Cerebral autoregulation is the brain’s intrinsic ability to maintain a relatively constant cerebral blood flow (CBF) despite fluctuations in mean arterial pressure (MAP). In ischemic stroke, this autoregulatory capacity is often compromised in the penumbra, the region of tissue at risk of infarction but potentially salvageable. When autoregulation is impaired, the brain’s ability to dilate cerebral vessels in response to a drop in MAP is diminished. Conversely, in the presence of intact autoregulation, a moderate increase in MAP can lead to vasodilation and increased CBF, potentially improving perfusion to the ischemic penumbra. Thrombolytic agents, such as alteplase, work by dissolving the occluding thrombus, facilitating reperfusion. However, the success of reperfusion and the subsequent salvage of ischemic tissue are critically dependent on the underlying hemodynamic state and the brain’s ability to utilize the restored blood flow. If autoregulation is severely impaired, even with successful recanalization, the ischemic tissue may not benefit optimally. The penumbra might remain hypoperfused due to fixed vascular resistance or even become susceptible to hemorrhagic transformation if MAP rises too high without compensatory vasodilation. Therefore, understanding the state of cerebral autoregulation is paramount in predicting the response to thrombolysis and guiding management strategies. The question focuses on identifying the scenario where the benefits of thrombolysis are most likely to be compromised due to a failure in the brain’s intrinsic mechanisms to adapt to altered perfusion pressures. A severely impaired autoregulatory capacity means the brain cannot effectively respond to changes in blood pressure to maintain adequate flow to the penumbra, thus limiting the benefit of reperfusion achieved by thrombolysis.

The question probes the understanding of neuroinflammatory mechanisms in the context of acute ischemic stroke and the potential therapeutic implications of targeting specific inflammatory pathways. The core concept is the biphasic nature of neuroinflammation post-stroke: an initial pro-inflammatory cascade followed by a later, potentially neuroprotective or reparative phase. Microglia, the resident immune cells of the brain, play a pivotal role in this process, undergoing activation and polarization into different phenotypes. M1 microglia are typically associated with pro-inflammatory cytokine release (e.g., TNF-α, IL-1β, IL-6), contributing to neuronal damage and blood-brain barrier disruption. Conversely, M2 microglia are linked to anti-inflammatory effects, phagocytosis of debris, and promotion of tissue repair. In the scenario described, a patient presents with a large territory ischemic stroke, and the diagnostic imaging confirms cytotoxic edema in the MCA territory. The question asks about the most likely predominant microglial phenotype in the initial hours post-stroke. During the acute phase (within the first few hours to a day), the primary response to ischemic injury is the activation of microglia into a pro-inflammatory (M1-like) phenotype. This activation is triggered by damage-associated molecular patterns (DAMPs) released from injured cells. These activated M1 microglia then release a cascade of inflammatory mediators that exacerbate the initial ischemic damage, leading to further neuronal dysfunction and death, and contributing to the expansion of the infarct core and penumbra. Therefore, the predominant microglial phenotype in the initial hours is M1.

The core of this question lies in understanding the interplay between cerebral autoregulation, blood pressure management, and the potential for reperfusion injury in the context of acute ischemic stroke. Cerebral autoregulation is the brain’s intrinsic ability to maintain a relatively constant cerebral blood flow (CBF) despite fluctuations in mean arterial pressure (MAP). This autoregulation typically operates within a MAP range of approximately 50-150 mmHg. Below this range, CBF becomes pressure-dependent, and above it, CBF is maintained until the upper limit of autoregulation is reached, after which CBF increases passively with MAP. In an acute ischemic stroke, particularly when reperfusion therapies like thrombolysis or mechanical thrombectomy are considered, the penumbra (the area of brain tissue at risk but not yet infarcted) is highly dependent on collateral circulation and maintained perfusion pressure. Aggressively lowering blood pressure in a patient with impaired autoregulation can further compromise blood flow to the penumbra, potentially expanding the infarct core. Conversely, in the absence of significant autoregulatory dysfunction, a controlled rise in blood pressure might be beneficial to augment collateral flow and improve reperfusion. The scenario describes a patient with an acute large vessel occlusion stroke, who has received mechanical thrombectomy with successful reperfusion. Post-procedure, their MAP is 140 mmHg. Given the successful reperfusion, the goal is to optimize CBF to the salvaged penumbra. While hypertension is a risk factor, in the immediate post-reperfusion period, maintaining adequate perfusion pressure is paramount. Abruptly lowering the MAP significantly, especially below the typical autoregulatory plateau, could jeopardize the reperfused tissue. Therefore, a strategy that avoids precipitous drops in blood pressure and aims to maintain a MAP that supports optimal perfusion without exacerbating hypertensive risks is preferred. A MAP of 130 mmHg represents a controlled reduction that is less likely to compromise reperfusion compared to a more aggressive drop, while still addressing the elevated blood pressure. This approach balances the need to prevent hemorrhagic transformation and other complications of hypertension with the critical requirement of ensuring adequate blood flow to the newly reperfused brain tissue. The physiological rationale is to avoid reducing the perfusion pressure below the lower limit of autoregulation, which could be shifted to the right in patients with chronic hypertension or acute stroke.

The question probes the understanding of the interplay between cerebral autoregulation and the efficacy of reperfusion therapies in acute ischemic stroke, specifically in the context of the American Board of Psychiatry and Neurology – Subspecialty in Vascular Neurology curriculum. The core concept is that impaired cerebral autoregulation, often indicated by a reduced pressure reactivity index (PRx), signifies a brain that is less able to adapt to changes in cerebral perfusion pressure (CPP). In such a compromised state, a rapid increase in CPP, as might occur with aggressive blood pressure management or successful reperfusion, could paradoxically lead to hyperemia and exacerbate edema or even hemorrhage in the vulnerable penumbra. Therefore, a patient with a significantly negative PRx (indicating impaired autoregulation) would necessitate a more cautious approach to blood pressure management post-thrombectomy to avoid potential iatrogenic harm. The other options represent less nuanced or incorrect interpretations. Maintaining a specific CPP range without considering autoregulatory capacity is insufficient. While reperfusion is the goal, the *method* of achieving it and managing post-reperfusion hemodynamics is critical. Focusing solely on the initial infarct core size neglects the dynamic physiological state of the penumbra and the impact of autoregulation.

The question probes the understanding of the interplay between cerebral autoregulation, blood pressure management, and the potential for reperfusion injury in the context of acute ischemic stroke treated with endovascular thrombectomy. Following successful mechanical reperfusion of a large vessel occlusion in the middle cerebral artery (MCA), the brain tissue is vulnerable to secondary injury mechanisms. Cerebral autoregulation, the brain’s intrinsic ability to maintain stable cerebral blood flow (CBF) despite fluctuations in mean arterial pressure (MAP), is often impaired in the ischemic penumbra and immediately post-reperfusion. A precipitous drop in MAP, particularly below the lower limit of autoregulation, can lead to a further reduction in CBF to already compromised areas, exacerbating ischemia and potentially leading to hemorrhagic transformation. Conversely, maintaining a MAP that is too high can increase the risk of systemic hypertension-related complications and potentially worsen vasogenic edema or hemorrhage in the reperfused territory. Therefore, a carefully titrated intravenous infusion of a vasopressor, such as norepinephrine, to maintain a MAP within a specific, slightly elevated range (e.g., 110-130 mmHg) is generally recommended. This range aims to ensure adequate perfusion pressure to the reperfused brain tissue while minimizing the risk of hypertension-induced complications. The rationale is to support the compromised autoregulatory capacity and prevent a hypoperfusion state. Lowering the MAP too aggressively (e.g., to 140 mmHg) increase the risk of hemorrhagic complications and edema. The specific target MAP is often guided by institutional protocols and individual patient factors, but a moderate elevation is a common strategy to optimize reperfusion and recovery.

The question probes the understanding of the interplay between cerebral autoregulation and the efficacy of reperfusion therapies in acute ischemic stroke, specifically in the context of a patient with pre-existing hypertension. Cerebral autoregulation is the brain’s intrinsic ability to maintain a relatively constant cerebral blood flow (CBF) despite fluctuations in mean arterial pressure (MAP). This autoregulation occurs within a specific pressure range, typically between a lower limit of \( \approx 50-60 \) mmHg and an upper limit of \( \approx 150-160 \) mmHg. Below the lower limit, CBF declines; above the upper limit, CBF increases passively, and autoregulation is lost. In a patient with chronic hypertension, the autoregulatory curve is often shifted to the right. This means that their autoregulation operates effectively at higher MAPs, and the lower limit of autoregulation is elevated. For instance, a patient with a history of poorly controlled hypertension might have a lower limit of autoregulation around \( \approx 80-90 \) mmHg or even higher. Mechanical thrombectomy aims to restore blood flow to an ischemic brain territory. However, the success and safety of this procedure, particularly regarding reperfusion injury and the risk of hemorrhagic transformation, are influenced by the MAP. During and after thrombectomy, maintaining adequate MAP is crucial to ensure successful reperfusion and prevent secondary ischemia. If the MAP is too low, even if it’s within the normal range for a healthy individual, it might fall below the elevated lower limit of autoregulation in a hypertensive patient, leading to inadequate perfusion of the ischemic penumbra and potentially worsening the outcome. Conversely, excessively high MAP can increase the risk of hemorrhagic transformation, especially in areas with a compromised blood-brain barrier. Therefore, the optimal management strategy involves carefully titrating blood pressure to ensure it is above the patient’s individual lower limit of autoregulation, thereby maximizing the chances of successful reperfusion without unduly increasing the risk of complications. This requires a nuanced understanding of the patient’s specific physiological state, including their history of hypertension and its likely impact on their autoregulatory capacity. The goal is to achieve a MAP that supports collateral flow and recanalization while minimizing the risk of secondary hemorrhage.

The question probes the understanding of the interplay between cerebral autoregulation and the efficacy of reperfusion therapies in acute ischemic stroke. Cerebral autoregulation is the brain’s intrinsic ability to maintain a relatively constant cerebral blood flow (CBF) despite fluctuations in mean arterial pressure (MAP). This is achieved through changes in cerebral vascular resistance. In healthy individuals, this autoregulation is effective across a wide range of MAPs, typically between 50 and 150 mmHg. However, in the context of acute ischemic stroke, particularly in the penumbra, autoregulation can be impaired. When autoregulation is compromised, CBF becomes more dependent on the systemic blood pressure. For patients receiving intravenous thrombolysis (IVT) with alteplase, maintaining adequate blood pressure is crucial to ensure sufficient perfusion pressure to the ischemic penumbra, thereby maximizing the benefit of reperfusion and minimizing the risk of hemorrhagic transformation. The American Heart Association/American Stroke Association guidelines recommend specific blood pressure targets for patients receiving IVT: systolic blood pressure (SBP) less than 185 mmHg and diastolic blood pressure (DBP) less than 110 mmHg. This target range aims to facilitate reperfusion without unduly increasing the risk of intraparenchymal hemorrhage. If autoregulation is severely impaired, a lower MAP might lead to inadequate perfusion of the penumbra, limiting the effectiveness of thrombolysis. Conversely, excessively high blood pressure could increase the risk of bleeding. Therefore, the optimal management strategy involves a careful balance. Mechanical thrombectomy, a more advanced reperfusion technique, often requires higher target blood pressures to ensure adequate flow through the opened cerebral vasculature, especially when collateral circulation is poor. The rationale behind the specific blood pressure targets for IVT is to support the perfusion pressure gradient across the ischemic territory, assuming some degree of preserved autoregulation or to compensate for its impairment, thereby promoting recanalization and salvaging the penumbra. The calculation is conceptual, focusing on understanding the physiological principle rather than a numerical result. The core concept is that maintaining a sufficient perfusion pressure gradient, influenced by systemic blood pressure and cerebral autoregulation, is paramount for successful reperfusion therapy in acute ischemic stroke.

The question probes the understanding of the interplay between cerebral autoregulation and the efficacy of reperfusion therapies in acute ischemic stroke, specifically in the context of a patient with pre-existing severe hypertension. Cerebral autoregulation is the brain’s intrinsic ability to maintain relatively constant cerebral blood flow (CBF) despite fluctuations in mean arterial pressure (MAP). In healthy individuals, this occurs within a MAP range of approximately 50-150 mmHg. However, chronic severe hypertension can lead to a rightward shift of this autoregulatory curve, meaning the brain requires a higher MAP to maintain adequate CBF. In the scenario presented, the patient has a history of severe hypertension, implying a blunted or shifted autoregulatory capacity. Following a large territory ischemic stroke, reperfusion therapy (such as mechanical thrombectomy) aims to restore blood flow. However, if the autoregulatory reserve is compromised, simply increasing systemic blood pressure to overcome a theoretical perfusion deficit might not be effective and could even be detrimental. In fact, excessively high blood pressure in a setting of impaired autoregulation can lead to complications like hypertensive encephalopathy or hemorrhagic transformation of the infarct. The optimal management strategy, therefore, involves a nuanced approach to blood pressure management. While maintaining adequate perfusion is crucial, it must be balanced against the risk of exacerbating underlying autoregulatory dysfunction. The goal is to achieve a blood pressure that supports collateral flow and reperfusion without exceeding the patient’s compromised autoregulatory capacity. This often means targeting a slightly higher blood pressure than in normotensive individuals, but not excessively high, and closely monitoring neurological status and imaging for signs of complications. The concept of maintaining a MAP within a range that supports collateral flow while minimizing the risk of secondary injury is paramount. For a patient with severe chronic hypertension, this range might be higher than the typical 110-130 mmHg often targeted, but it is not unlimited. The most appropriate approach is to maintain a MAP that supports collateral circulation and reperfusion without inducing further damage, which necessitates careful titration and monitoring, often guided by perfusion imaging or transcranial Doppler findings, rather than a blanket high-pressure target.

The scenario describes a patient with a confirmed large vessel occlusion (LVO) in the left middle cerebral artery (MCA) territory, presenting within the established time window for endovascular therapy. The patient’s National Institutes of Health Stroke Scale (NIHSS) score is 22, indicating a significant neurological deficit. The core infarct volume is estimated at 75 mL, and the penumbra, representing salvageable brain tissue, is estimated at 40 mL. The goal of endovascular therapy in such cases is to restore blood flow and salvage the ischemic penumbra. The core infarct is irreversibly damaged. Therefore, the maximum potentially salvageable brain tissue is limited by the size of the penumbra. The calculation to determine the maximum potential salvageable brain tissue is straightforward: Potentially Salvageable Tissue = Penumbra Volume Potentially Salvageable Tissue = 40 mL This value represents the volume of brain tissue that is hypoperfused but not yet infarcted, and thus has the potential to be recovered with timely reperfusion. The core infarct volume of 75 mL is already lost. The total ischemic volume is the sum of the core infarct and the penumbra, which is \(75 \text{ mL} + 40 \text{ mL} = 115 \text{ mL}\). However, the question specifically asks for the *potentially salvageable* tissue. This is a critical concept in vascular neurology, emphasizing the importance of rapid diagnosis and intervention to maximize the benefit of reperfusion therapies. Understanding the interplay between core infarct and penumbra on advanced imaging, such as DWI and perfusion imaging, is fundamental for patient selection for endovascular treatment at institutions like American Board of Psychiatry and Neurology – Subspecialty in Vascular Neurology University. The decision-making process hinges on accurately quantifying these volumes to predict functional outcomes and guide treatment strategies, aligning with the university’s commitment to evidence-based and patient-centered care in cerebrovascular diseases.

The question probes the understanding of neuroinflammatory mechanisms in the context of acute ischemic stroke, specifically focusing on the role of glial cells and their downstream effects. In acute ischemic stroke, reperfusion injury is a critical phase where the restoration of blood flow, while necessary for salvaging tissue, paradoxically exacerbates neuronal damage. This exacerbation is largely mediated by an intense inflammatory response. Microglia, the resident immune cells of the central nervous system, are rapidly activated upon ischemia. Initially, they adopt a pro-inflammatory phenotype (often termed M1-like), releasing a cascade of cytokines such as tumor necrosis factor-alpha (TNF-\(\alpha\)), interleukin-1 beta (IL-1\(\beta\)), and reactive oxygen species (ROS). These mediators contribute to neuronal dysfunction and death, disrupt the blood-brain barrier integrity, and recruit peripheral immune cells. Astrocytes also play a dual role, initially attempting to support neuronal survival but later contributing to inflammation and glial scar formation. The interplay between activated microglia and astrocytes, along with the release of chemokines, amplifies the inflammatory milieu. This sustained neuroinflammation can lead to secondary neuronal injury, extending the infarct core and affecting penumbral tissue. Therefore, understanding the sequence and impact of these glial-mediated inflammatory processes is crucial for developing targeted therapeutic strategies aimed at mitigating reperfusion injury. The correct approach involves recognizing that the initial pro-inflammatory activation of microglia, followed by their interaction with astrocytes and the release of cytotoxic mediators, forms the core of this detrimental process.

The question probes the understanding of the interplay between cerebral autoregulation, blood pressure, and the potential for reperfusion injury in the context of acute ischemic stroke management. Cerebral autoregulation is the brain’s intrinsic ability to maintain relatively constant cerebral blood flow (CBF) despite fluctuations in mean arterial pressure (MAP). This autoregulation is typically effective within a MAP range of approximately 50-150 mmHg in healthy individuals. However, in chronic hypertension, this autoregulatory curve is shifted to the right, meaning the brain requires a higher MAP to maintain adequate CBF. When a patient with chronic hypertension experiences an ischemic stroke, their autoregulatory capacity is often impaired, and the lower limit of autoregulation is elevated. The goal of blood pressure management in acute ischemic stroke is to ensure adequate perfusion pressure to the ischemic penumbra without exacerbating hemorrhage or causing further ischemic damage. For patients treated with intravenous thrombolysis (e.g., alteplase), a common guideline is to maintain systolic blood pressure (SBP) below 185 mmHg and diastolic blood pressure (DBP) below 110 mmHg. If the SBP exceeds 185 mmHg or DBP exceeds 110 mmHg, it is recommended to lower the blood pressure. Conversely, for patients undergoing mechanical thrombectomy, the blood pressure targets can be more permissive, often allowing SBP up to 180 mmHg and DBP up to 105 mmHg, or even higher in some protocols, to ensure adequate collateral flow and perfusion pressure to the ischemic territory, especially if there is evidence of collateral failure or a large perfusion deficit. The rationale behind this more permissive approach is to maximize the chance of successful reperfusion by providing adequate driving pressure, thereby potentially improving the salvage of ischemic brain tissue. However, this must be balanced against the risk of hemorrhagic transformation. Considering a patient with a known history of chronic hypertension who has undergone successful mechanical thrombectomy for a large vessel occlusion, maintaining adequate perfusion pressure is paramount. A blood pressure of SBP 160 mmHg and DBP 90 mmHg (MAP = \(90 + \frac{160-90}{3} \approx 113\) mmHg) is generally considered appropriate in this scenario. This level provides sufficient driving pressure to perfuse the penumbra and support collateral flow without significantly increasing the risk of hemorrhagic complications, especially given the underlying hypertension which implies a potentially elevated lower limit of autoregulation. Lowering the blood pressure further, for instance to SBP 130 mmHg, might compromise perfusion in a territory that relies on higher pressures due to impaired autoregulation, potentially leading to a larger infarct core or failed reperfusion. Conversely, allowing significantly higher pressures (e.g., SBP 200 mmHg) would increase the risk of hemorrhage. Therefore, a controlled but adequate blood pressure range is crucial.

The core of this question lies in understanding the interplay between cerebral autoregulation, blood pressure, and the risk of hemorrhagic transformation in acute ischemic stroke. Cerebral autoregulation is the brain’s ability to maintain a relatively constant cerebral blood flow (CBF) despite fluctuations in mean arterial pressure (MAP). This autoregulation typically operates within a MAP range of approximately 50-150 mmHg. Below this range, CBF becomes pressure-dependent, and above it, there’s an increased risk of hypertensive encephalopathy and potential vessel rupture. In the context of acute ischemic stroke, particularly after reperfusion therapies like thrombolysis or mechanical thrombectomy, the ischemic penumbra is vulnerable. The goal of blood pressure management is to ensure adequate perfusion to the salvageable brain tissue without exacerbating edema or causing hemorrhage. A MAP of 130 mmHg, while within the autoregulatory range, represents the upper end of this range for many individuals, especially those with pre-existing hypertension, where the autoregulatory curve may be shifted to the right. Maintaining a MAP at this level, particularly in the presence of a large territory infarct or significant edema, increases the transmural pressure across weakened vessel walls in the reperfused area, thereby elevating the risk of hemorrhagic transformation. Conversely, a lower MAP, such as 110 mmHg, would be more aligned with maintaining perfusion pressure to the penumbra while minimizing the risk of vessel rupture. The American Heart Association/American Stroke Association guidelines for acute ischemic stroke management recommend maintaining systolic blood pressure below 185 mmHg and diastolic blood pressure below 110 mmHg for patients receiving IV thrombolysis, and below 220/120 mmHg for those not receiving thrombolysis but eligible for mechanical thrombectomy. However, these are upper limits, and the optimal target MAP is often lower, particularly in the context of preventing hemorrhagic transformation. A MAP of 130 mmHg (which corresponds to a systolic pressure of approximately 170-180 mmHg, depending on the diastolic pressure) is considered too high for a patient with a large territory ischemic stroke and potential reperfusion, as it significantly increases the risk of hemorrhagic conversion. Therefore, a MAP of 110 mmHg is the most appropriate target to balance perfusion and reduce hemorrhagic risk.

The core of this question lies in understanding the interplay between cerebral autoregulation, blood pressure, and the potential for reperfusion injury in the context of acute ischemic stroke management. Cerebral autoregulation is the brain’s intrinsic ability to maintain relatively constant cerebral blood flow (CBF) despite fluctuations in mean arterial pressure (MAP). This autoregulation typically operates within a MAP range of approximately 50-150 mmHg. Below this range, CBF becomes pressure-dependent, and above it, CBF may increase disproportionately, potentially leading to edema and exacerbating injury. In acute ischemic stroke, particularly after reperfusion therapies like thrombolysis or mechanical thrombectomy, the affected brain tissue is vulnerable. While maintaining adequate perfusion pressure is crucial to prevent secondary ischemia, excessively high blood pressure can worsen hemorrhagic transformation and vasogenic edema. Conversely, overly aggressive blood pressure lowering can compromise collateral flow to the ischemic penumbra, hindering recovery and potentially expanding the infarct core. The American Board of Psychiatry and Neurology – Subspecialty in Vascular Neurology emphasizes a nuanced approach to blood pressure management in acute stroke. Current guidelines, such as those from the American Heart Association/American Stroke Association, suggest permissive hypertension in the absence of thrombolysis or mechanical thrombectomy, allowing blood pressure to be as high as \(185/110\) mmHg, provided there are no contraindications. This approach aims to maximize CBF to the ischemic penumbra, leveraging the brain’s remaining autoregulatory capacity. However, following successful reperfusion, especially with mechanical thrombectomy, the autoregulatory capacity may be impaired, and the risk of hemorrhagic transformation increases. Therefore, a more cautious approach to blood pressure reduction is often warranted to prevent reperfusion injury. A target blood pressure of less than \(180/105\) mmHg is generally recommended post-thrombectomy, with gradual reduction rather than abrupt lowering. This strategy balances the need for adequate perfusion with the risk of complications. The scenario describes a patient who has undergone successful mechanical thrombectomy for an anterior circulation large vessel occlusion. The patient’s blood pressure is elevated at \(195/115\) mmHg. The most appropriate management strategy involves a controlled reduction of blood pressure to prevent complications such as hemorrhagic transformation and cerebral edema, while still ensuring adequate perfusion to the reperfused territory. Aggressively lowering the blood pressure to a normotensive range (e.g., \(<140/90\) mmHg) could compromise collateral flow and worsen the ischemic outcome. Allowing the blood pressure to remain uncontrolled at \(195/115\) mmHg carries a significant risk of hemorrhagic complications. Therefore, a gradual reduction to a target below \(180/105\) mmHg is the most prudent approach, reflecting the current understanding of post-reperfusion management in vascular neurology.

The question probes the understanding of the interplay between cerebral autoregulation, blood pressure management, and the potential for secondary injury in the context of acute ischemic stroke. In a patient with a large territory ischemic stroke, the penumbra is at risk due to reduced perfusion. Cerebral autoregulation, the brain’s ability to maintain blood flow despite fluctuations in systemic blood pressure, is compromised in the ischemic region. Maintaining adequate mean arterial pressure (MAP) is crucial to ensure sufficient collateral flow to the penumbra. A MAP below a critical threshold can lead to further ischemic damage, while excessively high MAP can exacerbate edema and hemorrhage risk, particularly in reperfusion settings. For a patient with an acute ischemic stroke, guidelines generally recommend maintaining a MAP that supports perfusion to the ischemic penumbra without significantly increasing the risk of hemorrhagic transformation. While specific target MAPs can vary based on reperfusion status and individual patient factors, a common approach is to maintain MAP in the range of \(110-130\) mmHg for patients not receiving thrombolysis, and potentially higher if reperfusion therapy is being considered or has been administered, provided there are no contraindications. This range aims to optimize collateral flow to the hypoperfused areas. Lowering blood pressure too aggressively can compromise this critical perfusion pressure, leading to expansion of the infarct core and worsening neurological deficit. Conversely, uncontrolled hypertension can increase the risk of hemorrhagic conversion of the infarct, especially after thrombolysis or in the presence of microvascular disease. Therefore, a strategy that supports perfusion without inducing excessive pressure is paramount. The correct approach involves careful monitoring and titration of blood pressure to achieve a target MAP that balances the need for adequate cerebral perfusion with the risk of complications.

The question probes the understanding of neuroinflammatory mechanisms in the context of acute ischemic stroke and the potential therapeutic targets. Specifically, it focuses on the role of microglial activation and the downstream signaling pathways that contribute to secondary brain injury. Microglia, the resident immune cells of the central nervous system, undergo activation upon ischemic insult. This activation involves the release of pro-inflammatory cytokines, chemokines, and reactive oxygen species, which can exacerbate neuronal damage. Tumor necrosis factor-alpha (TNF-\(\alpha\)) is a key pro-inflammatory cytokine released by activated microglia. Its signaling cascade often involves the activation of nuclear factor-kappa B (NF-\(\kappa\)B), a transcription factor that promotes the expression of genes involved in inflammation and apoptosis. Therefore, inhibiting TNF-\(\alpha\) or its downstream signaling pathways, such as NF-\(\kappa\)B activation, represents a promising therapeutic strategy to mitigate secondary brain injury in ischemic stroke. Other options are less directly involved in the primary microglial-mediated inflammatory cascade following ischemia. While astrocytes play a role in neuroinflammation, their primary contribution in this context is often secondary to microglial activation or involves different signaling pathways. Interleukin-10 (IL-10) is an anti-inflammatory cytokine, and its enhancement would be a beneficial strategy, not a target for inhibition in this scenario. Platelet-activating factor (PAF) is involved in inflammation but is not the central mediator of the microglial-cytokine-NF-\(\kappa\)B axis in the same way as TNF-\(\alpha\).

The question probes the understanding of the interplay between cerebral autoregulation and the efficacy of reperfusion therapies in acute ischemic stroke. Cerebral autoregulation is the brain’s intrinsic ability to maintain a stable cerebral blood flow (CBF) despite fluctuations in mean arterial pressure (MAP). This autoregulation is typically characterized by a plateau phase where CBF remains constant as MAP increases, followed by a steep phase where CBF increases linearly with MAP. The lower limit of autoregulation (LLA) is the MAP below which CBF begins to decline. In the context of acute ischemic stroke, particularly during reperfusion therapies like mechanical thrombectomy, understanding the autoregulatory capacity of the affected hemisphere is crucial. A patient with impaired autoregulation, especially if their baseline MAP is below their LLA, will experience a significant drop in CBF if their MAP is lowered. Conversely, if autoregulation is intact, the brain can tolerate a wider range of MAPs. The scenario describes a patient with a large vessel occlusion in the MCA who has undergone successful mechanical thrombectomy. Post-procedure, the patient’s MAP is managed. The question asks about the optimal MAP management strategy considering the patient’s autoregulatory status. If autoregulation is intact, the brain can maintain adequate perfusion even with a moderate increase in MAP, which can help overcome any residual microvascular resistance and promote collateral flow to the ischemic penumbra. Therefore, maintaining a MAP at the higher end of the normal range, or even slightly elevated, is often beneficial to ensure adequate perfusion pressure across the potentially compromised cerebrovasculature. This approach supports the concept of “permissive hypertension” in certain stroke scenarios to maximize collateral recruitment and reperfusion. If autoregulation is impaired, a lower MAP could lead to a critical reduction in CBF, exacerbating the ischemic injury. Therefore, maintaining a higher MAP would be essential to prevent this. Considering the goal of optimizing reperfusion and recovery after successful thrombectomy, maintaining a MAP that ensures adequate perfusion pressure to the affected brain tissue is paramount. This generally translates to a higher target MAP compared to a patient with intact autoregulation and no stroke, as the ischemic brain often requires higher perfusion pressures to overcome impaired autoregulation and microvascular dysfunction. The optimal MAP target is often guided by monitoring techniques that assess autoregulation, but in the absence of such specific data, a general principle is to support perfusion. The correct approach involves maintaining a MAP that is sufficient to ensure adequate perfusion pressure to the ischemic penumbra, especially after successful reperfusion. This typically means avoiding hypotension and often targeting a MAP that is at the higher end of the normal range or slightly elevated, to compensate for potential autoregulatory dysfunction and promote collateral flow. This strategy aims to maximize the benefit of reperfusion therapy by ensuring that the restored blood flow can effectively reach and perfuse the salvageable brain tissue.

The scenario describes a patient with a confirmed large vessel occlusion (LVO) in the left middle cerebral artery (MCA) territory, presenting within the established time window for mechanical thrombectomy. The core principle guiding the decision-making process in such a case, particularly at an institution like the American Board of Psychiatry and Neurology – Subspecialty in Vascular Neurology University, is the maximization of salvageable brain tissue while minimizing the risk of complications. Advanced neuroimaging, specifically diffusion-weighted imaging (DWI) and perfusion imaging (e.g., CT perfusion or MR perfusion), is crucial for this assessment. The mismatch between the infarct core (identified by DWI, representing irreversibly damaged tissue) and the penumbra (identified by perfusion imaging, representing hypoperfused but potentially salvageable tissue) dictates the potential benefit of reperfusion therapies. A significant mismatch, characterized by a large penumbra relative to the core infarct, strongly favors mechanical thrombectomy. While the National Institutes of Health Stroke Scale (NIHSS) quantifies stroke severity, and the Alberta Stroke Program Early CT Score (ASPECTS) provides a qualitative assessment of early ischemic changes on non-contrast CT, neither directly quantifies the volume of salvageable tissue in the same way as perfusion imaging. Therefore, the most critical imaging parameter to guide the decision for mechanical thrombectomy in this context is the volume of the ischemic penumbra, as determined by perfusion imaging, in relation to the infarct core. This approach aligns with the evidence supporting reperfusion therapies in LVO stroke, aiming to restore blood flow to areas at risk of infarction. The explanation emphasizes the quantitative assessment of salvageable brain tissue, which is a cornerstone of modern stroke management and a key area of focus in vascular neurology training at advanced institutions.

The question probes the understanding of neuroinflammatory mechanisms in the context of acute ischemic stroke and the potential therapeutic targets. Specifically, it focuses on the role of microglial activation and the downstream signaling pathways that contribute to secondary brain injury. Microglia, the resident immune cells of the central nervous system, are rapidly activated following an ischemic insult. This activation involves a complex cascade of events, including the release of pro-inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6) and chemokines, as well as the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). These mediators can exacerbate neuronal damage, disrupt the blood-brain barrier, and contribute to the expansion of the infarct core. Among the signaling pathways involved in microglial activation and subsequent inflammatory responses, the Toll-like receptor (TLR) pathway, particularly TLR4, plays a crucial role. TLR4 can be activated by endogenous damage-associated molecular patterns (DAMPs) released from injured cells, such as high-mobility group box 1 (HMGB1) protein, or by exogenous pathogen-associated molecular patterns (PAMPs) if an infection is present. Activation of TLR4 leads to the recruitment of adaptor proteins like MyD88, which in turn activates downstream kinases such as IRAKs and TRAF6. This complex then activates transcription factors, most notably NF-κB, which translocates to the nucleus and promotes the transcription of genes encoding pro-inflammatory cytokines and adhesion molecules. Therefore, targeting the NF-κB pathway represents a significant therapeutic strategy to mitigate neuroinflammation and reduce secondary brain injury in acute ischemic stroke. Inhibiting NF-κB activation would dampen the production of pro-inflammatory mediators, potentially preserving neuronal function and improving outcomes. Other pathways, such as the inflammasome pathway (e.g., NLRP3 inflammasome), also contribute to neuroinflammation in stroke, but the NF-κB pathway is a central regulator of the early inflammatory cascade initiated by microglial activation in response to ischemic damage.

The question probes the understanding of the interplay between cerebral autoregulation and the efficacy of reperfusion therapies in acute ischemic stroke, specifically in the context of a patient with pre-existing hypertension. Cerebral autoregulation is the brain’s intrinsic ability to maintain relatively constant cerebral blood flow (CBF) despite fluctuations in mean arterial pressure (MAP). This autoregulation is typically achieved by adjusting cerebral vascular resistance. In healthy individuals, this mechanism is effective over a wide range of MAPs. However, chronic hypertension can lead to a downward shift in the autoregulation curve, meaning that the brain’s ability to maintain CBF at lower MAPs is impaired. When a patient with chronic hypertension experiences an ischemic stroke, the affected brain tissue is already compromised due to reduced blood flow. If thrombolytic therapy or mechanical thrombectomy is administered, restoring blood flow to the ischemic penumbra is crucial. However, if the autoregulation curve is significantly shifted, a lower MAP, even within the typical therapeutic target range for post-stroke management, might lead to hypoperfusion in the vulnerable penumbra. Conversely, a higher MAP might be necessary to ensure adequate perfusion pressure across the autoregulatory threshold. Therefore, understanding the patient’s autoregulatory capacity, often inferred from their chronic blood pressure management and potentially assessed with advanced imaging, is paramount. The optimal blood pressure target during and after reperfusion therapy aims to balance the risk of hemorrhagic transformation with the need to perfuse the ischemic territory. For patients with chronic hypertension, a slightly higher blood pressure target might be considered to overcome the impaired autoregulation and ensure adequate collateral flow to the penumbra, thereby maximizing the benefit of reperfusion and minimizing infarct expansion. This nuanced approach is critical for optimizing outcomes in vascular neurology, aligning with the advanced training expected at the American Board of Psychiatry and Neurology – Subspecialty in Vascular Neurology University.

The scenario describes a patient with a known history of atrial fibrillation presenting with acute neurological deficits consistent with an ischemic stroke. The core of the question lies in understanding the optimal initial management strategy for such a patient, specifically regarding the timing and modality of reperfusion therapy. Given the patient’s presentation within the therapeutic window for intravenous thrombolysis (IV tPA) and the absence of contraindications, this is the first-line treatment. Mechanical thrombectomy is indicated for large vessel occlusions (LVOs) in the anterior circulation, and while this patient may have an LVO, the decision to proceed with thrombectomy is typically made after initial assessment and often in conjunction with or following consideration of IV tPA, depending on institutional protocols and imaging findings. However, the question asks for the *most appropriate initial step* in a patient presenting with symptoms suggestive of acute ischemic stroke and a known risk factor like atrial fibrillation, within the established time window. The immediate administration of IV tPA, after confirming eligibility through imaging and clinical assessment, is the standard of care to restore blood flow and limit infarct progression. Delaying reperfusion therapy to solely pursue mechanical thrombectomy without initial consideration of IV tPA would be suboptimal if the patient is a candidate for both, as IV tPA can be administered more rapidly and may even facilitate subsequent thrombectomy. Therefore, the initial focus should be on administering IV tPA if indicated.

The question probes the understanding of the interplay between cerebral autoregulation and the management of acute ischemic stroke, specifically in the context of blood pressure targets following reperfusion therapy. In a patient receiving intravenous thrombolysis for an anterior circulation large vessel occlusion, the goal is to maintain adequate cerebral perfusion pressure (CPP) to support the penumbra and prevent secondary injury. Cerebral autoregulation, the brain’s ability to maintain a stable blood flow despite fluctuations in mean arterial pressure (MAP), is often impaired in the ischemic territory. A commonly cited guideline, such as those from the American Heart Association/American Stroke Association, suggests maintaining systolic blood pressure (SBP) below 185 mmHg and diastolic blood pressure (DBP) below 110 mmHg before and during IV thrombolysis. After successful reperfusion, particularly with mechanical thrombectomy, the target blood pressure is often relaxed to allow for collateral recruitment and to prevent reperfusion injury, which can be exacerbated by abrupt hypotension. A target SBP between 140-180 mmHg is generally considered appropriate in the absence of contraindications, aiming to optimize CPP without inducing hypertensive complications. This range supports autoregulation in the affected hemisphere while mitigating the risk of hemorrhagic transformation. Therefore, maintaining a systolic blood pressure within the 140-180 mmHg range is crucial. This range acknowledges the need for sufficient perfusion pressure to support the ischemic penumbra and facilitate collateral flow, especially after successful reperfusion, while also being mindful of the increased risk of intracranial hemorrhage associated with uncontrolled hypertension. The precise upper limit is often guided by the presence and extent of reperfusion, the success of endovascular intervention, and the absence of contraindications to permissive hypertension.

The question probes the understanding of neuroinflammatory mechanisms in the context of acute ischemic stroke, specifically focusing on the role of microglia and their activation states. In the initial phase of ischemic stroke, a cascade of events leads to neuronal injury and death. Microglia, the resident immune cells of the central nervous system, are rapidly activated in response to this insult. Their activation is not monolithic; they can adopt different phenotypes, broadly categorized as pro-inflammatory (M1-like) and anti-inflammatory/resolving (M2-like). Following an ischemic event, the initial microglial response is predominantly pro-inflammatory, characterized by the release of cytokines such as tumor necrosis factor-alpha (TNF-\(\alpha\)), interleukin-1 beta (IL-1\(\beta\)), and reactive oxygen species (ROS). This M1-like activation contributes to excitotoxicity, blood-brain barrier disruption, and further neuronal damage. However, as the stroke progresses, microglia can transition to an M2-like phenotype, which is associated with phagocytosis of cellular debris, release of neurotrophic factors, and promotion of tissue repair. The question asks to identify the primary cellular mediator responsible for the early release of pro-inflammatory cytokines in the ischemic penumbra. While astrocytes and infiltrating peripheral immune cells (like neutrophils and macrophages) also play roles in neuroinflammation, microglia are the first responders and are critically involved in orchestrating the initial inflammatory milieu. Their rapid activation and release of inflammatory mediators are central to the early pathogenesis of ischemic stroke. Therefore, understanding the distinct roles and temporal activation patterns of these cells is crucial for developing targeted therapeutic strategies. The correct answer focuses on the initial, detrimental inflammatory response driven by microglia.

The question probes the understanding of neuroinflammatory mechanisms in the context of acute ischemic stroke and the potential therapeutic targets. Specifically, it focuses on the role of microglial activation and the downstream signaling pathways that contribute to secondary neuronal injury. The explanation will detail how activated microglia release pro-inflammatory cytokines and reactive oxygen species, exacerbating the ischemic penumbra. It will then highlight how inhibiting the NLRP3 inflammasome, a key intracellular sensor complex that triggers the release of IL-1β and IL-18, can mitigate this inflammatory cascade. This approach is supported by research demonstrating that targeting NLRP3 activation can reduce infarct volume and improve functional outcomes in preclinical stroke models. Therefore, the most appropriate therapeutic strategy would involve modulating this specific inflammatory pathway.

The scenario describes a patient with acute ischemic stroke who has received intravenous thrombolysis with alteplase. The subsequent development of a new neurological deficit, specifically aphasia and right hemiparesis, occurring 24 hours post-thrombolysis, strongly suggests a complication. Given the timing and the nature of the deficit, the most likely cause is a hemorrhagic transformation of the infarct. Hemorrhagic transformation can occur after thrombolytic therapy, especially in larger infarcts or in patients with certain risk factors. While other complications like recurrent ischemia or cerebral edema are possible, the sudden onset of new focal deficits after a period of stability points towards bleeding within the infarcted tissue. The management of suspected hemorrhagic transformation involves immediate cessation of anticoagulation (if ongoing), repeat neuroimaging to confirm the bleed and assess its extent, and supportive care. The question asks for the most appropriate next step in management. Confirming the presence and extent of hemorrhage via non-contrast CT is paramount before any further interventions. Therefore, obtaining a non-contrast head CT is the immediate priority.

The question probes the understanding of neuroinflammation’s role in acute ischemic stroke, specifically focusing on the post-reperfusion inflammatory cascade. Following successful mechanical thrombectomy, reperfusion of ischemic brain tissue initiates a complex inflammatory response. Microglia and astrocytes become activated, releasing pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-\(\alpha\)) and interleukin-1 beta (IL-1\(\beta\)). This inflammatory milieu contributes to secondary neuronal injury through mechanisms like excitotoxicity, oxidative stress, and disruption of the blood-brain barrier (BBB). Neutrophils and monocytes infiltrate the affected area, further exacerbating inflammation and contributing to reperfusion injury. The BBB, initially compromised by ischemia, becomes further disrupted by inflammatory mediators and cellular infiltration, leading to vasogenic edema and potential hemorrhagic transformation. Understanding this intricate interplay is crucial for developing targeted neuroprotective strategies that aim to mitigate the detrimental effects of the inflammatory response post-reperfusion. Therefore, the most accurate description of the primary inflammatory event post-reperfusion in the context of successful mechanical thrombectomy involves the activation of resident glial cells and subsequent infiltration of peripheral immune cells, leading to a cascade of cytokine release and BBB breakdown.

The core of this question lies in understanding the differential impact of specific neuroinflammatory mediators on the integrity of the blood-brain barrier (BBB) following an ischemic insult. In the context of acute ischemic stroke, the release of matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, is a critical factor in BBB breakdown. These enzymes degrade tight junction proteins like occludin and claudins, increasing vascular permeability. Tumor necrosis factor-alpha (TNF-$\alpha$) is a potent pro-inflammatory cytokine that upregulates the expression of MMPs and also directly affects endothelial cell function, contributing to BBB disruption. Interleukin-6 (IL-6) also plays a role in inflammation and BBB permeability, but its direct contribution to the rapid breakdown of tight junctions in the immediate post-stroke period is generally considered less pronounced than that of TNF-$\alpha$ and MMPs. Transforming growth factor-beta (TGF-$\beta$) is a pleiotropic cytokine with complex roles; while it can have protective effects in some contexts, it can also promote fibrosis and angiogenesis, and its direct role in acute BBB breakdown in ischemic stroke is less established as a primary driver compared to the inflammatory cascade initiated by TNF-$\alpha$ and executed by MMPs. Therefore, the combination of TNF-$\alpha$ and MMPs represents the most significant immediate threat to BBB integrity in this scenario, leading to vasogenic edema and exacerbating the ischemic injury.

The question probes the understanding of the interplay between cerebral autoregulation and reperfusion injury in the context of acute ischemic stroke management, specifically when considering mechanical thrombectomy. Cerebral autoregulation is the brain’s intrinsic ability to maintain relatively constant cerebral blood flow (CBF) despite fluctuations in mean arterial pressure (MAP). This autoregulation is typically impaired in the ischemic penumbra, the area of brain tissue at risk but not yet infarcted. During reperfusion, particularly after successful mechanical thrombectomy, there is a rapid restoration of blood flow to the ischemic territory. However, if autoregulation remains significantly compromised, this sudden influx of blood at a potentially elevated MAP can lead to a breakdown of the blood-brain barrier (BBB), increased capillary hydrostatic pressure, and subsequent hemorrhagic transformation or cytotoxic edema. This phenomenon is known as reperfusion injury. The critical factor in mitigating this risk is the restoration of functional autoregulation. If autoregulation is preserved or recovers, the brain can better buffer the changes in MAP, preventing excessive CBF and minimizing BBB disruption. Therefore, maintaining a MAP that is sufficient to perfuse the brain but not so high as to overwhelm compromised autoregulation is paramount. The optimal MAP target post-thrombectomy, in the absence of contraindications, is generally considered to be within a range that supports adequate perfusion without exacerbating reperfusion injury. While specific targets can vary based on individual patient factors and institutional protocols, a commonly accepted approach is to maintain a MAP that is slightly above the patient’s baseline or a level that ensures adequate collateral flow without inducing hyperperfusion. A MAP of \( \geq 80 \) mmHg is often considered a reasonable starting point to ensure adequate perfusion pressure, especially in the context of potentially impaired autoregulation, while avoiding excessive pressure that could worsen BBB integrity. Conversely, a MAP that is too low (\( < 70 \) mmHg) might compromise perfusion to the vulnerable penumbra, while excessively high MAP (\( > 120 \) mmHg) could exacerbate BBB breakdown in the setting of impaired autoregulation. Therefore, a MAP target in the range of \( 80-100 \) mmHg is often favored to balance perfusion needs with the risk of reperfusion injury.

The question probes the understanding of neuroinflammatory mechanisms in the context of acute ischemic stroke management, specifically concerning the timing and rationale for initiating immunomodulatory therapies beyond standard reperfusion. In acute ischemic stroke, the initial insult triggers a complex cascade of events, including excitotoxicity, ionic shifts, and ultimately, programmed cell death. However, a significant component of secondary brain injury arises from the inflammatory response. Microglia and astrocytes become activated, releasing pro-inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6) and chemokines, which recruit peripheral immune cells like neutrophils and monocytes to the ischemic penumbra. While this inflammatory response is intended to clear debris and initiate repair, an uncontrolled or prolonged inflammatory process can exacerbate neuronal damage, disrupt the blood-brain barrier, and contribute to edema formation, ultimately worsening the neurological deficit. The critical window for intervention in acute ischemic stroke typically focuses on restoring blood flow to salvage the ischemic penumbra, primarily through thrombolysis or mechanical thrombectomy. However, emerging research and clinical interest are exploring the potential benefits of modulating the inflammatory cascade. The rationale for delaying broad immunomodulatory therapy until after reperfusion is multifaceted. Firstly, suppressing the immune system too early could impair the necessary clearance of necrotic tissue and hinder the initial stages of endogenous repair. Secondly, many immunomodulatory agents have their own risks, including increased susceptibility to infection, which might be amplified if administered during the vulnerable period immediately following reperfusion. Therefore, a staged approach is often considered, where initial management prioritizes reperfusion and hemodynamic stability, followed by a consideration of immunomodulatory strategies once the immediate reperfusion phase is complete and the patient is stabilized, allowing for a more targeted intervention against the detrimental aspects of the inflammatory response without compromising essential early protective mechanisms. This approach aims to mitigate the secondary injury driven by inflammation while preserving the benefits of reperfusion.