Adapting Clinical Practice of Thrombolysis for Acute Ischemic Stroke Beyond 4.5 Hours: A Review of the Literature

Simpkins, Alexis N; Tahsili-Fahadan, Pouya; Buchwald, Natalie; Prey, Justin De; Farooqui, Amreen; Mugge, Luke; Ranasinghe, Tamra; Senetar, Alexander J; Echevarria, Franklin D.; Alvi, Muhammad; Wu, Ona

doi:10.1016/j.jstrokecerebrovasdis.2021.106059

Cited by 9 publications

(19 citation statements)

References 68 publications

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“…The primary goal of cerebral ischemic stroke therapy is to restore blood ow as quickly as possible by recanalizing the occluded vessel, such as thrombolytic, which have achieved remarkable progress in clinical [42,43]. But the time window of interventions is limited to the rst hours after stroke [6,44]. Therefore, complementary or alternative therapies are urgently needed to reduce stroke-related mortality and disability beyond this short period.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, complementary or alternative therapies are urgently needed to reduce stroke-related mortality and disability beyond this short period. In rodents, studies have shown that the post-ischemic "sensitive period" last for the rst 4 weeks, putatively the equivalent of the early stroke in humans [6,44]. Besides, the critical period of post-stroke rehabilitation is around the 5-14 days after ischemia [34].…”

Section: Discussionmentioning

confidence: 99%

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Activation of CREB-BDNF Pathway in Pyramidal Neurons in the Hippocampus Improves the Neurological Outcome of Mice with Ischemic Stroke

et al. 2022

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Cerebral ischemia is characterized by several pathological reaction evolving over time. Hyperactivation of glutamatergic neurons is the main factor leading to excitotoxicity which potentiates oxidative stress and triggers the mechanisms of neural apoptosis after cerebral ischemia. However, it is unclear whether glutamate in the ventral hippocampal Cornus Ammonis 1 (vCA1) acts a part in neurological de cits, pain perception, anxiety and depression induced by ischemic-stroke. We investigated the effects of chemogenetic inhibition or activation of vCA1 pyramidal neurons which are mainly glutamatergic neurons on sequelae induced by cerebral ischemia. Our results revealed that inhibition of vCA1 pyramidal neurons by chemogenetics alleviated neurological de cits, pain perception, anxiety and depression caused by cerebral ischemia in mice, but activation of vCA1 pyramidal neurons had limited effects. Moreover, we found that stroke was accompanied by decreased levels of cAMP-response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in vCA1, which are modulated by glutamate.In this study, overexpression of CREB protein in pyramidal neurons in vCA1 by AAV virus signi cantly upregulated the content of BDNF and ameliorated the dysfunction induced by ischemic-stroke. Our results demonstrated activation of CREB-BDNF pathway in vCA1 pyramidal neurons signi cantly improved neurological de cits, pain perception, anxiety and depression induced by ischemic-stroke.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Activation of CREB-BDNF Pathway in Pyramidal Neurons in the Hippocampus Improves the Neurological Outcome of Mice with Ischemic Stroke

et al. 2022

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“…6,7 MRI DWI-FLAIR mismatch is an imaging biomarker thought to be a surrogate for the duration of ischemia reflected by the degree of hyperintensity on the FLAIR sequence and, thus, the irreversibility of the damage within the ischemic region. 4 Visual inspection or direct measurement of the hyperintensity on the FLAIR sequence corresponding to the DWI region of interest compared with the contralateral or unaffected side with a ratio of <1.15 is used to assess the duration/degree of ischemia (Figure 2). 4 In this clinical scenario, large, small, cortical, and subcortical acute ischemic stroke can be screened for thrombolysis.…”

Section: Illustrative Teaching Casesmentioning

confidence: 99%

“…4 Many new extended time window studies incorporating thrombolysis and endovascular therapy are still enrolling, and their protocols have been previously reviewed in a separate publication. 4 Safety of thrombolysis in DWI-FLAIR mismatch patients 4.5 to 24 hours from onset is unknown. 4 In our case, the patient's noncontrast head CT scan demonstrated early ischemic changes with a corresponding perfusion lesion without a large perfusion mismatch.…”

Section: Illustrative Teaching Casesmentioning

confidence: 99%

Imaging Caveats to Consider When Screening for Thrombolysis in the Extended Time Window

Reyes,

Ahmadi,

Kieran

et al. 2023

Stroke

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“…It is known that approximately 85% of strokes are ischemic (cerebral infarction) [ 3 ], and the main goal in the treatment of ischemic stroke is to restore tissue perfusion in the ischemic zone to reduce the size of the infarction by maintaining blood flow [ 4 ]. However, the use of the intravenous recombinant tissue plasminogen activator for recanalization and restoration of blood flow in the ischemic area of the brain due to the narrow time window and the risk of hemorrhagic complications is possible only for a small proportion of patients [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Vinpocetine as a Neuroprotective Agent in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

Panda

Ramachandran²,

Suthar

2022

Neurocrit Care

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Background Vinpocetine as a neuroprotective agent is effective in acute ischemic stroke in some randomized controlled trials (RCTs). Since the last systematic review has been published in 2008, which didn’t find conclusive evidence favoring its use, two more RCTs have also been completed. Methods Relevant electronic databases were searched with a suitable combination of Medical Subject Headings terms to detect publications describing RCTs exploring the safety and efficacy of vinpocetine in patients with acute ischemic stroke. The risk of bias was determined by using the Cochrane Collaboration’s tool for assessing the risk of bias in RCTs after full-text review and relevant data extraction. Higgins and Thompson’s I 2 method was used to assess heterogeneity in studies. The presence of publication bias was assessed by Egger’s test. We used a random effect model when I 2 was more than 50% and a fixed-effect model for other parameters. Results Four placebo-controlled RCTs enrolling a total of 601 and 236 patients in vinpocetine and placebo groups, respectively, were included. The number of patients with death or significant disability was lower in the vinpocetine group than that in the placebo group at both 1 and 3 months (relative risk 0.80, 95% confidence interval [CI] 0.65–0.99 and relative risk 0.67, CI 0.48–0.92, p = 0.04 and 0.02, respectively). The degree of disability in participants at 1 month and 3 months was also lower in vinpocetine group than that in the placebo group (standardized mean difference (SMD) 0.49, 95% CI 0.03–0.95 and SMD 1.22, CI 0.23–2.24, p = 0.001 and 0.04, respectively). Change in mini-mental state examination score compared with baseline at trial enrolment was also better in the vinpocetine group than in the placebo group (pooled weighted mean difference 0.92, 95% CI 0.02–1.82, p = 0.04). Conclusions Vinpocetine has some promising efficacy in patients with ischemic stroke when used in the acute stage in reducing the disability, but presently there is not enough evidence to suggest that it also reduces case fatality. More double-blind, placebo-controlled RCTs of adequate sample size are needed before making recommendations for the routine administration of vinpocetine for all patients with acute ischemic stroke. Supplementary Information The online version contains supplementary material available at 10.1007/s12028-022-01499-y.

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Adapting Clinical Practice of Thrombolysis for Acute Ischemic Stroke Beyond 4.5 Hours: A Review of the Literature

Cited by 9 publications

References 68 publications

Activation of CREB-BDNF Pathway in Pyramidal Neurons in the Hippocampus Improves the Neurological Outcome of Mice with Ischemic Stroke

Activation of CREB-BDNF Pathway in Pyramidal Neurons in the Hippocampus Improves the Neurological Outcome of Mice with Ischemic Stroke

Imaging Caveats to Consider When Screening for Thrombolysis in the Extended Time Window

Safety and Efficacy of Vinpocetine as a Neuroprotective Agent in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

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