{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:24:05Z","timestamp":1791473045138,"version":"4.3.4"},"reference-count":49,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["25-25-00101"],"award-info":[{"award-number":["25-25-00101"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In this study, the neurorehabilitation potential of combined and isolated intermittent hypercapnia and hypoxia exposure was evaluated following photochemically induced cerebral thrombosis in rats. Particular attention was given to the roles of possible neuroplasticity mechanisms mediated by VEGF and BDNF, as well as the potential of hypercapnic\u2013hypoxic interventions to synergistically amplify the therapeutic effects of pharmacological neuroprotectants during recovery. A total of 50 male Wistar rats were randomly assigned to five equal groups (n = 10 per group), each undergoing a course of respiratory interventions lasting 30 min per day for 15 sessions. The groups included (1) a normobaric hypoxia (PO2 \u2248 90 mmHg) group, (2) a permissive hypercapnia (PCO2 \u2248 50 mmHg) group, (3) a combined hypercapnic hypoxia (PO2 \u2248 90 mmHg, PCO2 \u2248 50 mmHg) group, (4) a control group, and (5) a sham-operated group. Following the rehabilitation protocol, animals exposed to hypercapnic hypoxia exhibited a two-fold reduction in stroke volume compared with controls, significant improvement in motor coordination (as assessed via the rotarod test), and marked upregulation of VEGF and BDNF expression within the ischemic brain region. Notably, only the HH group showed a decrease in serum neuron-specific enolase (NSE) levels. These findings indicate that hypercapnic hypoxia exerts a possible neurorehabilitative effect after focal ischemic injury, superior to that of isolated hypoxia or hypercapnia. Possible mechanisms underlying this outcome may involve activation of neurotrophic (BDNF) and angiogenic (VEGF) signaling pathways.<\/jats:p>","DOI":"10.3390\/ijms262412019","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T09:36:39Z","timestamp":1765791399000},"page":"12019","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neuroplastic Effects Induced by Hypercapnic Hypoxia in Rat Focal Ischemic Stroke Are Driven via BDNF and VEGF Signaling"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3650-6121","authenticated-orcid":false,"given":"Pavel P.","family":"Tregub","sequence":"first","affiliation":[{"name":"Brain Science Institute, Russian Center of Neurology and Neurosciences, 125367 Moscow, Russia"},{"name":"Department of Pathophysiology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"},{"name":"Scientific and Educational Resource Center \u201cInnovative Technologies of Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis\u201d, RUDN University, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel A.","family":"Chekulaev","sequence":"additional","affiliation":[{"name":"Brain Science Institute, Russian Center of Neurology and Neurosciences, 125367 Moscow, Russia"},{"name":"Department of Pathophysiology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgy M.","family":"Zembatov","sequence":"additional","affiliation":[{"name":"Brain Science Institute, Russian Center of Neurology and Neurosciences, 125367 Moscow, Russia"},{"name":"Department of Pathophysiology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia D.","family":"Namiot","sequence":"additional","affiliation":[{"name":"Brain Science Institute, Russian Center of Neurology and Neurosciences, 125367 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Ignatyuk","sequence":"additional","affiliation":[{"name":"Scientific and Educational Resource Center \u201cInnovative Technologies of Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis\u201d, RUDN University, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8347-4556","authenticated-orcid":false,"given":"Dmitrii A.","family":"Atiakshin","sequence":"additional","affiliation":[{"name":"Scientific and Educational Resource Center \u201cInnovative Technologies of Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis\u201d, RUDN University, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arseniy K.","family":"Berdnikov","sequence":"additional","affiliation":[{"name":"Brain Science Institute, Russian Center of Neurology and Neurosciences, 125367 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaripat Sh.","family":"Manasova","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter F.","family":"Litvitskiy","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4869-5465","authenticated-orcid":false,"given":"Vladimir P.","family":"Kulikov","sequence":"additional","affiliation":[{"name":"Department of Ultrasound and Functional Diagnostics, Altay State Medical University, 656040 Barnaul, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Yuan, H., Liu, J., Gu, Y., Ji, X., and Nan, G. (2022). 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