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Administering MSC‐Derived Exosomes After Hypoxia‐Induced Seizures in Neonatal Rats Improved Cognitive Function and Delayed the Onset of Epilepsy in Adulthood, Likely by Reducing Inflammation and Oxidative Stress

P. Arvin,Maryam Khombi Shooshtari,Ali Asadirad,Kowsar Bavarsad,Azam Asgarihafshejani,Y. Farbood,A. Sarkaki,Samireh Ghafouri

Published 2025 in Developmental Neurobiology

ABSTRACT

Hypoxia‐induced neonatal seizures (HINSs) are a major cause of long‐term 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‐exosomes) in a rat model of HINS, leveraging their anti‐inflammatory and neuroregenerative properties. Forty‐nine male and female Wistar rats were divided into four groups: (1) control + saline, (2) control + exosome, (3) hypoxia + saline, and (4) hypoxia + exosome. Neonatal rats (postnatal day 10) were subjected to hypoxia (5% O2 for 15 min). Sixty minutes after the onset of hypoxia induction, pups received either MSC‐exosomes (30 µg/100 µL) or saline for 12 consecutive days (lactation period). Behavioral tests, hippocampal tissue analysis (for RT‐PCR and oxidative stress markers), and pentylenetetrazole (PTZ) kindling were performed at P60–P61.

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