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Post-stroke, therapeutic hypothermia so far did not translate into clinically applicable therapies due to hypothermia-associated side-effects compromising patient outcome. The hypothalamus contains two major thermoregulatory centers in the ventrolateral preoptic area (vlPOA) and dorsomedial hypothalamus (DMH), which are connected via gamma-aminobutyric acid (GABA)-ergic fibers. Using chemogenetic and optogenetic approaches, we explored the role of this GABAergic projection in regulating body temperature responses, cerebral blood flow, and ischemic injury in\n                    <jats:italic>Vgat-cre<\/jats:italic>\n                    mice exposed to transient middle cerebral artery occlusion (MCAo). Using a chemogenetic approach, we show that the inhibition of a set of GABAergic DMH\n                    <jats:sup>VGAT<\/jats:sup>\n                    neurons, which under physiological conditions induces hyperthermia, is essential to drive hypothermia, which decreases cerebral blood flow post-MCAo and protects against ischemic reperfusion injury via mechanisms involving preservation of astrocytic homeostatic functions. This phenotype is recapitulated by the optogenetic activation of the GABAergic vlPOA\n                    <jats:sup>VGAT<\/jats:sup>\n                    neurons, which similarly induces hypothermia and protects against ischemic injury. The GABAergic vlPOA\n                    <jats:sup>VGAT<\/jats:sup>\n                    DMH pathway provides a potent target for neuroprotective therapies. We hypothesize that modulating central temperature responses via this pathway may not elicit the undesirable side effects associated with exogenous brain cooling.\n                  <\/jats:p>","DOI":"10.1038\/s41419-026-08536-0","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T21:45:53Z","timestamp":1773179153000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["GABAergic ventrolateral preoptic projection to dorsomedial hypothalamus recapitulates post-ischemic neuroprotection by hypothermia"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9192-5014","authenticated-orcid":false,"given":"Pelin","family":"Dilsiz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4237-8580","authenticated-orcid":false,"given":"Aysenur","family":"Ozpinar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9659-2124","authenticated-orcid":false,"given":"Buse","family":"Balaban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2562-1068","authenticated-orcid":false,"given":"Halil \u0130brahim","family":"Ko\u00e7","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serdar","family":"Altunay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9752-7508","authenticated-orcid":false,"given":"Saltuk Bu\u011fra","family":"Baltac\u0131","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma Zehra","family":"Hapil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1222-9211","authenticated-orcid":false,"given":"Thorsten Roland","family":"Doeppner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egor","family":"Dzyubenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa \u00c7a\u011flar","family":"Beker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0198-3152","authenticated-orcid":false,"given":"Dirk Matthias","family":"Hermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ertu\u011frul","family":"K\u0131l\u0131\u00e7","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"8536_CR1","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/nn2027","volume":"11","author":"K Nakamura","year":"2008","unstructured":"Nakamura K, Morrison SF. 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