ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2022
Female-specific neuroprotection after ischemic stroke by vitronectin-focal adhesion kinase inhibition.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Systolic blood pressure and early neurological deterioration in minor stroke: A post hoc analysis of ARAMIS trial.CNS neuroscience & therapeutics · 2024Trial
- The potential and therapeutic advances of the integrin family in neurological disorders.Neural regeneration research · 2026Article
- Cross-Platform Proteomics and Machine Learning Algorithms Nominate Plasma Biomarkers of Stroke Diagnosis.Journal of the American Heart Association · 2026Article
- Neuronal deterioration associated with hyperexcitability under mild chronic cerebral hypoperfusion.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025Article
- Endothelial lincRNA-p21 alleviates cerebral ischemia/reperfusion injury by maintaining blood-brain barrier integrity.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Physical exercise-induced circAnks1b upregulation promotes protective endoplasmic reticulum stress and suppresses apoptosis via miR-130b-5p/Pak2 signaling in an ischemic stroke model.CNS neuroscience & therapeutics · 2024Article
- Gender-specific prognosis models reveal differences in subarachnoid hemorrhage patients between sexes.CNS neuroscience & therapeutics · 2024Article
- Alterations in metabolome and lipidome in patients with in-stent restenosis.CNS neuroscience & therapeutics · 2024Article
- Transcending Traditional Treatment: The Therapeutical Potential of Nanovesicles for Transdermal Baclofen Delivery in Repeated Traumatic Brain Injury.Advanced pharmaceutical bulletin · 2024Article
- PV and SST neurons in the anterior cingulate cortex regulate social disorders in adulthood induced by sensory abnormalities in childhood.CNS neuroscience & therapeutics · 2024Article
- The p75 neurotrophin receptor attenuates secondary thalamic damage after cortical infarction by promoting angiogenesis.CNS neuroscience & therapeutics · 2024Article
- A role for astrocytic insulin-like growth factor I receptors in the response to ischemic insult.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Identification of Potential Neddylation-related Key Genes in Ischemic Stroke based on Machine Learning Methods.Molecular neurobiology · 2024Article
- Astrocyte focal adhesion kinase reduces passive stress coping by inhibiting ciliary neurotrophic factor only in female mice.Neurobiology of stress · 2024Article
- Astrocyte KDM4A mediates chemokines and drives neutrophil infiltration to aggravate cerebral ischemia and reperfusion injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Identification and characterization of extrachromosomal circular DNA in large-artery atherosclerotic stroke.Journal of cellular and molecular medicine · 2024Article
- Group 2 innate lymphoid cells suppress neuroinflammation and brain injury following intracerebral hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- CCL5 mediated astrocyte-T cell interaction disrupts blood-brain barrier in mice after hemorrhagic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Sex-stratified genome-wide association and transcriptome-wide Mendelian randomization studies reveal drug targets of heart failure.Cell reports. Medicine · 2024Article
- Growth arrest specific protein 6 alleviated white matter injury after experimental ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
We found that blood vitronectin (VTN) leaks into the brain and exacerbates tissue loss after stroke by increasing pro-inflammatory IL-6 expression in female, but not male, mice. VTN signals through integrins and downstream focal adhesion kinase (FAK). Here, a two day systemic treatment with a small molecule FAK inhibitor starting 6 h after middle cerebral artery occlusion reduced ipsilateral brain injury size by ∼40-45% at 7 and 14 d, as well as inflammation and motor dysfunction in wild-type female, but not male, mice. FAK inhibition also reduced IL-6 expression in the injured female striatum at 24 h by 62%. Inducible selective gene deletion of FAK in astrocytes also reduced acute IL-6 expression by 72% only in females, and mitigated infarct size by ∼80% and inflammation at 14 d after stroke. Lastly, VTN-/- females had better outcomes, but FAK inhibitor treatment had no additional protective or anti-inflammatory effects. Altogether, this suggests that VTN is detrimental in females primarily through FAK and that FAK inhibition provides neuroprotection (cerebroprotection) by reducing VTN-induced IL-6 expression in astrocytes. Thus, VTN signaling can be targeted to mitigate harmful inflammation with relevance to treatments for women with ischemic stroke, who often have worse outcomes than men.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.