{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T17:06:20Z","timestamp":1778864780377,"version":"3.51.4"},"reference-count":65,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005001","name":"Ahvaz Jundishapur University of Medical Sciences","doi-asserted-by":"publisher","award":["IR.AJUMS.ABHC.REC.1400.112"],"award-info":[{"award-number":["IR.AJUMS.ABHC.REC.1400.112"]}],"id":[{"id":"10.13039\/501100005001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Developmental Neurobiology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hypoxia\u2010induced neonatal seizures (HINSs) are a major cause of long\u2010term cognitive deficits and heightened epilepsy risk in adulthood. Early inflammatory responses following HINS contribute to these pathological outcomes. This study examined the sustained neuroprotective benefits of exosomes derived from mesenchymal stem cells (MSC\u2010exosomes) in a rat model of HINS, leveraging their anti\u2010inflammatory and neuroregenerative properties. Forty\u2010nine male and female Wistar rats were divided into four groups: (1) control\u00a0+\u00a0saline, (2) control\u00a0+\u00a0exosome, (3) hypoxia\u00a0+\u00a0saline, and (4) hypoxia\u00a0+\u00a0exosome. Neonatal rats (postnatal day 10) were subjected to hypoxia (5% O\n                    <jats:sub>2<\/jats:sub>\n                    for 15\u00a0min). Sixty minutes after the onset of hypoxia induction, pups received either MSC\u2010exosomes (30\u00a0\u00b5g\/100\u00a0\u00b5L) or saline for 12 consecutive days (lactation period). Behavioral tests, hippocampal tissue analysis (for RT\u2010PCR and oxidative stress markers), and pentylenetetrazole (PTZ) kindling were performed at P60\u2013P61.\n                  <\/jats:p>\n                  <jats:p>The study revealed that treatment with exosomes improved memory performance and reduced anxiety\u2010like behaviors in the hypoxia\u2010exposed group, as evidenced by the novel object recognition and elevated plus maze tests. These benefits were linked to decreased oxidative stress (lower malondialdehyde\/MDA levels), reduced pro\u2010inflammatory markers (interleukin\u20106 [IL\u20106] and tumor necrosis factor\u2010\u03b1 [TNF\u2010\u03b1]), and increased anti\u2010inflammatory signaling (higher IL\u201010) in the hippocampus. Although exosome therapy delayed the onset of epileptogenesis, it did not lessen the intensity of seizures. The results indicate that administering MSC\u2010derived exosomes after HINS can reduce susceptibility to PTZ\u2010induced kindling, alleviate neuroinflammation, regulate oxidative stress, and protect against long\u2010term cognitive impairments. Together, these findings highlight the potential of exosome\u2010based interventions in mitigating the delayed neurological effects of HINS during adolescence.<\/jats:p>","DOI":"10.1002\/dneu.23010","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T05:44:57Z","timestamp":1761025497000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Administering MSC\u2010Derived Exosomes After Hypoxia\u2010Induced Seizures in Neonatal Rats Improved Cognitive Function and Delayed the Onset of Epilepsy in Adulthood, Likely by Reducing Inflammation and Oxidative Stress"],"prefix":"10.1002","volume":"85","author":[{"given":"Parisa","family":"Arvin","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Ahvaz Jundishapur University of Medical Sciences  Ahvaz Iran"},{"name":"Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute Ahvaz Jundishapur University of Medical Sciences  Ahvaz Iran"},{"name":"Department of Nursing, Boroujerd Faculty of Medical Sciences Lorestan University of Medical Sciences  Khorramabad Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryam Khombi","family":"Shooshtari","sequence":"additional","affiliation":[{"name":"Chronic Renal Failure Research Center Ahvaz Jundishapur University of Medical Sciences  Ahvaz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Asadirad","sequence":"additional","affiliation":[{"name":"Department of Immunology, Faculty of Medicine Ahvaz Jundishapur University of Medical Sciences  Ahvaz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kowsar","family":"Bavarsad","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Ahvaz Jundishapur University of Medical Sciences  Ahvaz Iran"},{"name":"Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute Ahvaz Jundishapur University of Medical Sciences  Ahvaz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azam","family":"Asgarihafshejani","sequence":"additional","affiliation":[{"name":"Genetics and Development Department University Health Network  Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaghoob","family":"Farbood","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Ahvaz Jundishapur University of Medical Sciences  Ahvaz Iran"},{"name":"Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute Ahvaz Jundishapur University of Medical Sciences  Ahvaz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alireza","family":"Sarkaki","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Ahvaz Jundishapur University of Medical Sciences  Ahvaz Iran"},{"name":"Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute Ahvaz Jundishapur University of Medical Sciences  Ahvaz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samireh","family":"Ghafouri","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Ahvaz Jundishapur University of Medical Sciences  Ahvaz Iran"},{"name":"Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute Ahvaz Jundishapur University of Medical Sciences  Ahvaz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxres\/tfae159"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v6.i2.134"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110405"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2016-0260"},{"key":"e_1_2_11_6_1","volume-title":"Short Protocols in Molecular Biology: A Compendium of Methods from Current Protocols in Molecular Biology","author":"Ausubel F. 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