Time Course of Lesion Development in Patients With Acute Stroke

Schwamm, Lee H; Koroshetz, Walter J.; Sorensen, A. Gregory; Wang, Bing; Copen, W.A.; Budzik, Ronald F; Rordorf, Guy; Buonanno, Ferdinando S.; Schaefer, Pamela W.; González, R. Gilberto

doi:10.1161/01.str.29.11.2268

Cited by 323 publications

(150 citation statements)

References 27 publications

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“…26,80,81 Two studies, which serially imaged 14 and 21 patients each, suggested an increase in infarct volume that did not maximize until 3-5 days after the onset of ischemia. 81,83 Of course, even if infarct volume increases over time, this does not necessarily indicate that growth in infarct size will affect functional outcome after stroke. Recent work has begun to address this important question.…”

Section: Delayed Stroke Volume Growth In Humans: a Target For Intervementioning

confidence: 99%

Targeting Astrocytes for Stroke Therapy

2010

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Summary: Stroke remains a major health problem and is a leading cause of death and disability. Past research and neurotherapeutic clinical trials have targeted the molecular mechanisms of neuronal cell death during stroke, but this approach has uniformly failed to reduce stroke-induced damage or to improve functional recovery. Beyond the intrinsic molecular mechanisms inducing neuronal death during ischemia, survival and function of astrocytes is absolutely required for neuronal survival and for functional recovery after stroke. Many functions of astrocytes likely improve neuronal viability during stroke. For example, uptake of glutamate and release of neurotrophins enhances neuronal viability during ischemia. Under certain conditions, however, astrocyte function may compromise neuronal viability. For example, astrocytes may produce inflammatory cytokines or toxic mediators, or may release glutamate. The only clinical neurotherapeutic trial for stroke that specifically targeted astrocyte function focused on reducing release of S-100␤ from astrocytes, which becomes a neurotoxin when present at high levels. Recent work also suggests that astrocytes, beyond their influence on cell survival, also contribute to angiogenesis, neuronal plasticity, and functional recovery in the several days to weeks after stroke. If these delayed functions of astrocytes could be targeted for enhancing stroke recovery, it could contribute importantly to improving stroke recovery. This review focuses on both the positive and the negative influences of astrocytes during stroke, especially as they may be targeted for translation to human trials.

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Section: Delayed Stroke Volume Growth In Humans: a Target For Intervementioning

confidence: 99%

Targeting Astrocytes for Stroke Therapy

2010

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“…However, evidence suggest that cell-autonomous delayed apoptotic signaling plays a critical role in determining the ultimate burden of neuron loss after injury (Abe et al, 1995;Schwamm et al, 1998). Hypoxia is a potent stimulus for de novo gene expression, and sub-lethal hypoxic stress can enhance cell survival through the regulated expression of factors such as erythropoietin and vascular endothelial growth factor (Dirnagl et al, 2003;Jones and Bergeron, 2001).…”

Section: Introductionmentioning

confidence: 99%

Loss of c/EBP-β activity promotes the adaptive to apoptotic switch in hypoxic cortical neurons

Halterman

Jesus

Rempe

et al. 2008

Molecular and Cellular Neuroscience

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Understanding the mechanisms governing the switch between hypoxia-induced adaptive and pathological transcription may reveal novel therapeutic targets for stroke. Using an in vitro hypoxia model that temporally separates these divergent responses, we found apoptotic signaling was preceded by a decline in c/EBP-β activity and was associated with markers of ER-stress including transient eIF2α phosphorylation, and the delayed induction of the bZIP proteins ATF4 and CHOP-10. Pretreatment with the eIF2α phosphatase inhibitor salubrinal blocked the activation of caspase-3, indicating that ER-related stress responses are integral to this transition. Delivery of either full-length, or a transcriptionally inactive form of c/EBP-β protected cultures from hypoxic challenge, in part by inducing levels of the anti-apoptotic protein Bcl-2. These data indicate that the pathologic response in cortical neurons induced by hypoxia involves both the loss of c/EBP-β-mediated survival signals and activation of pro-death pathways originating from the endoplasmic reticulum.

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“…66 Natural history studies show that in patients with mismatch, the DWI lesion will usually expand into the larger PWI lesion if reperfusion does not occur. 60,67,68 This model has prompted the pursuit of therapies to prevent expansion of DWI lesions in patients with a clear DWI/PWI mismatch, even after the 3-h window for thrombolysis. DWI/PWI mismatch has been reported in up to 86.3% of acute stroke patients.…”

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

Neuroimaging of ischemia and infarction

Camargo

Koroshetz

2005

Neurotherapeutics

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Summary:Since the introduction of thrombolytic therapy as the foundation of acute stroke treatment, neuroimaging has rapidly advanced to empower therapeutic decision making. Diffusionweighted imaging is the most sensitive and accurate method for stroke detection, and, allied with perfusion-weighted imaging, provides information on the functional status of the ischemic brain. It can also help to identify a response to thrombolytic and neuroprotective therapies. Additionally, multimodal magnetic resonance imaging, including magnetic resonance angiography, offers information on stroke mechanism and pathophysiology that can guide long-term medical management. Multimodal computed tomography is a comprehensive, cost-effective, and safe stroke imaging modality that can be easily implemented in the emergency ward and that offers fast and reliable information with respect to the arterial and functional status of the ischemic brain. Accessibility, contraindications, cost, speed, and individual patient-determined features influence which is the best imaging modality to guide acute stroke management.

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Time Course of Lesion Development in Patients With Acute Stroke

Cited by 323 publications

References 27 publications

Targeting Astrocytes for Stroke Therapy

Targeting Astrocytes for Stroke Therapy

Loss of c/EBP-β activity promotes the adaptive to apoptotic switch in hypoxic cortical neurons

Neuroimaging of ischemia and infarction

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