{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T09:03:10Z","timestamp":1780045390420,"version":"3.53.1"},"reference-count":63,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,14]],"date-time":"2024-12-14T00:00:00Z","timestamp":1734134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["81870827"],"award-info":[{"award-number":["81870827"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Objectives: Dementia is becoming a major health problem in the world, and chronic brain ischemia is an established important risk factor in predisposing this disease. Astrocytes, as one major part of the blood\u2013brain barrier (BBB), are activated during chronic cerebral blood flow hypoperfusion. Reactive astrocytes have been classified into phenotype pro-inflammatory type A1 or neuroprotective type A2. However, the specific subtype change of astrocyte and the mechanisms of chronic brain ischemia are still unknown. Methods: In order to depict the phenotype changes and their possible roles during this process, a rat bilateral common carotid artery occlusion model (BCAO) was employed in the present study. Meanwhile, the signaling pathways that possibly regulate these changes were investigated as well. Results: After four-week occlusion, astrocytes in the cortex of BCAO rats were shown to be the A2 phenotype, identified by the significant up-regulation of S100a10 accompanied by the down-regulation of Connexin 43 (CX43) protein. Next, we established in vitro hypoxia models, which were set up by stimulating primary astrocyte cultures from rat cortex with cobalt chloride, low glucose, or\/and fibrinogen. Consistent with in vivo data, the cultured astrocytes also transformed into the A2 phenotype with the up-regulation of S100a10 and the down-regulation of CX43. In order to explore the mechanism of CX43 protein changes, C6 astrocyte cells were handled in both hypoxia and low-glucose stimulus, in which decreased pERK and pJNK expression were found. Conclusions: In conclusion, our data suggest that in chronic cerebral ischemia conditions, the gradual ischemic insults could promote the transformation of astrocytes into A2 type instead of A1 type, and the phosphorylation of CX43 was negatively regulated by the phosphorylation of ERK and JNK. Also, our data could provide some new evidence of how to leverage the endogenous astrocytes phenotype changes during CNS injury by promoting them to be \u201cprotector\u201d and not \u201cculprit\u201d.<\/jats:p>","DOI":"10.3390\/brainsci14121256","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T04:14:52Z","timestamp":1734322492000},"page":"1256","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Phenotype Changes of Astrocyte During Different Ischemia Conditions"],"prefix":"10.3390","volume":"14","author":[{"given":"Fei","family":"Meng","sequence":"first","affiliation":[{"name":"Cardiac Valve Center, Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 101100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0892-9909","authenticated-orcid":false,"given":"Junhui","family":"Wang","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/S0733-8619(05)70051-7","article-title":"Dementia","volume":"19","author":"Volicer","year":"2001","journal-title":"Neurol. 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