Maternal metformin protects developing auditory brainstem function after neonatal hypoxia-ischemia in a neonatal rat model.

Authors

Sei Eun Kim, Joo Young Kweon, Yong Joo Ahn, Jun Hee Kim

Published in

Clinical and experimental pediatrics. Sep 17, 2026. Epub Sep 17, 2026.

Abstract

Neonatal hypoxia-ischemia (HI) disrupts brain development and can impair sensory circuit maturation. However, how HI vulnerability is modified within developing auditory pathways remains poorly defined.
Metformin is used during pregnancy in select cases and modulates cellular energy signaling. Here, we tested whether maternal metformin administration during gestation alters functional and cellular outcomes in offspring brain after neonatal HI.
Pregnant rat dams received metformin in drinking water, and offspring rat pups underwent HI during early postnatal life. Auditory pathway function was assessed in vivo using auditory brainstem responses (ABRs), and cellular pathology within the medial nucleus of the trapezoid body (MNTB) was evaluated by immunohistochemistry across postinjury developmental time points.
HI significantly elevated click-evoked ABR thresholds and reduced wave II and III amplitudes, whereas maternal metformin exposure prevented the HI-induced click-threshold elevation and preserved wave II and III amplitudes without altering peripheral or central conduction times. Histologically, HI produced an age-dependent decline in MAP2-positive neuronal density in the MNTB, culminating in marked neuronal loss at later postnatal stages. Notably, maternal metformin partially rescued HI-associated reductions in MNTB neurons, with a parallel trend toward preservation of oligodendrocyte lineage cells.
Together, these findings indicate that maternal metformin administration during pregnancy enhances metabolic signaling and mitigates HI-related auditory brainstem dysfunction and cellular pathology in offspring, supporting maternal metabolic modulation as a determinant of neonatal sensory brain injury outcomes.

PMID:
42767666
Bibliographic data and abstract were imported from PubMed on 22 Sep 2026.

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