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bioRxiv · 10.1101/2025.09.18.677186

Low-frequency transcranial magnetic stimulation offers both immediate and delayed neuroprotection in neonatal hypoxia-ischemia model

Goussakov, I.·Synowiec, S.·Drobyshevsky, A.
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Abstract

Perinatal hypoxic-ischemic encephalopathy (HIE) is a leading cause of morbidity and mortality, and the current standard of care, therapeutic hypothermia, provides only partial neuroprotection. This study investigates the potential of low-frequency transcranial magnetic stimulation (LF-TMS) as a novel non-pharmacological adjunct therapy by targeting a key pathological mechanism of HIE: a persistent, pathological increase in glutamatergic synaptic transmission, or hypoxic long-term potentiation (hLTP). Using a neonatal mouse model of hypoxia-ischemia, we administered a single session of LF-TMS shortly after the hypoxic event. We then evaluated its effects on synaptic function via slice electrophysiology and on brain injury volume using serial MRI. Our results show that hypoxia-ischemia induced a significant and lasting synaptic potentiation in the brains penumbral region. A single LF-TMS treatment successfully reduced this elevated glutamatergic response to control levels, suggesting a therapeutic mechanism similar to long-term depression (LTD) by regulating AMPA receptor redistribution. Furthermore, LF-TMS provided significant neuroprotection, as demonstrated by a reduction in the volume of the ischemic core and penumbra 48 hours after the injury. LF-TMS did not alter excitability in sham-treated mice, confirming its safety as a targeted intervention for pathological conditions without affecting normal brain function. This study provides strong evidence that LF-TMS is a promising neuroprotective strategy that acutely and subacutely mitigates brain injury in a neonatal hypoxia-ischemia model.

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Goussakov, I., Synowiec, S., Drobyshevsky, A.. 2025-09-19. Low-frequency transcranial magnetic stimulation offers both immediate and delayed neuroprotection in neonatal hypoxia-ischemia model. https://doi.org/10.1101/2025.09.18.677186

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