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However, secondary damage often extends to anatomically distant regions, particularly the hippocampus. One of the early neuroendocrine responses to cerebral ischemia is activation of the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis. Increased release of corticosterone (CORT) by the adrenal glands into the bloodstream leads to its accumulation in the hippocampus. We hypothesize that this process may contribute to the hippocampal damage and underlie delayed cognitive and affective impairments following stroke. To test this, we investigated the levels of neurotrophic factors reflecting the neuroprotective potential of the hippocampus using two established middle cerebral artery occlusion (MCAO) models that differ in their effects on CORT production: the Koizumi et\u00a0al. (1986) model (MCAO1) and the Longa et\u00a0al. (1989) model (MCAO2). Although both models produced comparable neurological deficits, mortality rates, and infarct volumes, they differed markedly in endocrine and hippocampal responses. Significant increases in circulating CORT and its accumulation in both ipsilateral and contralateral hippocampus were observed only in MCAO1. Moreover, correlations between the CORT levels (in the blood and hippocampus) and both rat body weight and neurological deficit were stronger in MCAO1 than in MCAO2. In both acute models, brain-derived neurotrophic factor (BDNF) levels were elevated in the ipsilateral hippocampus, whereas the content of glial cell line-derived neurotrophic factor (GDNF) remained unchanged. In contrast, ciliary neurotrophic factor (CNTF) increased in the ipsilateral hippocampus only in MCAO2. These findings suggest that differential activation of the HPA axis and consequent variations in corticosteroid signaling in the hippocampus selectively modulate the neurotrophic response during the acute phase following MCAO.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1134\/s0006297925604162","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T10:27:42Z","timestamp":1785493662000},"page":"1187-1199","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Levels of Neurotrophic Factors in the Rat Hippocampus in the Acute Period after Middle Cerebral Artery Occlusion Are Associated with the Hypothalamic\u2013Pituitary\u2013Adrenal Axis Activation"],"prefix":"10.1134","volume":"91","author":[{"given":"Mikhail V.","family":"Onufriev","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia V.","family":"Moiseeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita R.","family":"Novikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel A.","family":"Kostryukov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia V.","family":"Gulyaeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"137","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"3065_CR1","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1007\/s00234-002-0846-3","volume":"44","author":"M. 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