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Ischemic stroke leads to severe outcomes, including permanent brain damage and neuronal dysfunction. Therefore, decreasing and preventing neuronal injuries caused by stroke has been the focus of therapeutic research. In recent years, many studies have shown that fluctuations in hormonal levels influence the prognosis of ischemic stroke. Thus, it is relevant to understand the role of hormones in the pathophysiological mechanisms of ischemic stroke for preventing and treating this health issue. Here, we investigate the contribution of the prolactin\/vasoinhibin axis, an endocrine system regulating blood vessel growth, immune processes, and neuronal survival, to the pathophysiology of ischemic stroke. Male mice with brain overexpression of prolactin or vasoinhibin by adeno\u2010associated virus (AAV) intracerebroventricular injection or lacking the prolactin receptor (<jats:italic>Prlr<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>) were exposed to transient middle cerebral artery occlusion (tMCAO) for 45\u2009min followed by 48\u2009h of reperfusion. Overexpression of vasoinhibin or the absence of the prolactin receptor led to an increased lesion volume and decreased survival rates in mice following tMCAO, whereas overexpression of prolactin had no effect. In addition, astrocytic distribution in the penumbra was altered, glial fibrillary acidic protein and S100b mRNA expressions were reduced, and interleukin\u20106 mRNA expression increased in the ischemic hemisphere of mice overexpressing vasoinhibin. Of note, prolactin receptor\u2010null mice (<jats:italic>Prlr<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>) showed a marked increase in serum vasoinhibin levels. Furthermore, vasoinhibin decreased astrocyte numbers in mixed hippocampal neuron\u2013glia cultures. These observations suggest that increased vasoinhibin levels may hinder astrocytes' protective reactivity. Overall, this study suggests the involvement of the prolactin\/vasoinhibin axis in the pathophysiology of ischemic stroke\u2010induced brain injury and provides insights into the impact of its dysregulation on astrocyte reactivity and lesion size. Understanding these mechanisms could help develop therapeutic interventions in ischemic stroke and other related neurological disorders.<\/jats:p>","DOI":"10.1111\/jne.13415","type":"journal-article","created":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T08:40:25Z","timestamp":1716972025000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The influence of the prolactin\/vasoinhibin axis on post\u2010stroke lesion volume, astrogliosis, and survival"],"prefix":"10.1111","volume":"36","author":[{"given":"Ximena","family":"Castillo","sequence":"first","affiliation":[{"name":"Instituto de Neurobiolog\u00eda Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM)  Quer\u00e9taro Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgina","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Instituto de Neurobiolog\u00eda Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM)  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