EphA4/Tie2 crosstalk regulates leptomeningeal collateral remodeling following ischemic stroke

Leptomeningeal anastomoses or pial collateral vessels play a critical role in cerebral blood flow (CBF) restoration following ischemic stroke. The magnitude of this adaptive response is postulated to be controlled by the endothelium, although the underlying molecular mechanisms remain under investigation. Here we demonstrated that endothelial genetic deletion, using EphA4fl/fl/Tie2-Cre and EphA4fl/fl/VeCahderin-CreERT2 mice and vessel painting strategies, implicated EphA4 receptor tyrosine kinase as a major suppressor of pial collateral remodeling, CBF, and functional recovery following permanent middle cerebral artery occlusion. Pial collateral remodeling is limited by the crosstalk between EphA4-Tie2 signaling in vascular endothelial cells, which is mediated through p-Akt regulation. Furthermore, peptide inhibition of EphA4 resulted in acceleration of the pial arteriogenic response. Our findings demonstrate that EphA4 is a negative regulator of Tie2 receptor signaling, which limits pial collateral arteriogenesis following cerebrovascular occlusion. Therapeutic targeting of EphA4 and/or Tie2 represents an attractive new strategy for improving collateral function, neural tissue health, and functional recovery following ischemic stroke.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

Related Links:

Condition:   Stroke, Ischemic Intervention:   Device: Transcranial direct current stimulation Sponsor:   Mahidol University Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   Hyperhomocysteinemia, Thrombotic, Cbs-Related;   Ischemic Stroke;   Epilepsy Intervention:   Genetic: Methylenetetrahydrofolate reductase (MTHFR) deficiency Sponsor:   Istanbul Medeniyet University Completed
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Authors: Kim HJ, Kang T, Kang MJ, Ahn HS, Sohn SY Abstract BACKGROUND: Hyperthyroidism is associated with various cardiovascular risk factors. However, the relationship between hyperthyroidism and myocardial infarction (MI) or stroke has not been fully elucidated; only a few studies have investigated the association of hyperthyroidism with survival after MI or stroke. METHODS: We included 59,021 hyperthyroid patients and 1,180,420 age- and sex-matched control cohort from the Korean National Health Insurance database. Blood pressure, body mass index (BMI), glucose and cholesterol level, and smoking history were ...
Source: Thyroid : official journal of the American Thyroid Association - Category: Endocrinology Tags: Thyroid Source Type: research
New brain imaging evidence of people who experience an ischemic stroke reveals differences between men and women.Medscape Medical News
Source: Medscape Neurology and Neurosurgery Headlines - Category: Neurology Tags: Neurology & Neurosurgery News Source Type: news
Authors: Osei-Owusu J, Yang J, Del Carmen Vitery M, Tian M, Qiu Z Abstract Severe local acidosis causes tissue damage and pain, and is associated with many diseases, including cerebral and cardiac ischemia, cancer, infection, and inflammation. However, the molecular mechanisms of the cellular response to extracellular acidic environment are not fully understood. We recently identified a novel and evolutionarily conserved membrane protein, PAC (also known as PACC1 or TMEM206), encoding the proton-activated chloride (Cl-) channel, whose activity is widely observed in human cell lines. We demonstrated that genetic del...
Source: Channels - Category: Molecular Biology Tags: Channels (Austin) Source Type: research
CONCLUSIONS: Melatonin protected SH SY5Y cells from OGD/R induced oxidative stress, inflammation, apoptosis, and autophagy by blocking NF-κB signaling and activating Nrf2/HO-1, Akt, and mTOR/p70S6K/4E-BP-1 pathways, thereby indicating that melatonin is a potential and novel therapeutic drug for ischemic stroke. PMID: 32096202 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
CONCLUSIONS: In patients with anterior cerebral artery-occluded AIS, the TC level is a promising prognosis marker for the IV thrombolysis outcome. PMID: 32096200 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
Conclusions regarding improvement in functional improvement cannot be drawn. Further trials are needed to strengthen the evidence on this topic. PMID: 32096199 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
CONCLUSIONS: MiR-155-5p accelerates cerebral I/R injury via targeting DUSP14 by regulating NF-κB and MAPKs signaling pathways. Inhibition of miR-155-5p significantly reduces apoptosis and brain injury. These results indicated that miR-155-5p plays a key role in cerebral I/R injury and has the potential to be explored as a new target for ischemic stroke. PMID: 32096190 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
Benjamin Y. Q. Tan, Prakash R Paliwal, Vijay K SharmaAnnals of Indian Academy of Neurology 2020 23(2):155-158 Ischemic stroke remains a significant health problem, which is expected to increase owing to an aging population. A considerable proportion of stroke patients suffer from gastrointestinal complications, including dysphagia, gastrointestinal hemorrhage, and constipation. Often, these complications adversely affect stroke outcomes. Recent research postulates the role of “brain-gut axis” in causing gut microbiota dysbiosis and various complications and outcomes. In this review, we present our current unde...
Source: Annals of Indian Academy of Neurology - Category: Neurology Authors: Source Type: research
More News: Biomedical Science | Genetics | Ischemic Stroke | Stroke