{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T01:23:32Z","timestamp":1768526612488,"version":"3.49.0"},"posted":{"date-parts":[[2025,9,19]]},"group-title":"Neuroscience","reference-count":18,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["1R01NS119251-01A1"],"award-info":[{"award-number":["1R01NS119251-01A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>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).<\/jats:p>\n                <jats:p>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 brain\u2019s 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.<\/jats:p>\n                <jats:p>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.<\/jats:p>","DOI":"10.1101\/2025.09.18.677186","type":"posted-content","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T23:40:17Z","timestamp":1758325217000},"source":"Crossref","is-referenced-by-count":0,"title":["Low-frequency transcranial magnetic stimulation offers both immediate and delayed neuroprotection in neonatal hypoxia-ischemia model"],"prefix":"10.64898","author":[{"given":"Ivan","family":"Goussakov","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvia","family":"Synowiec","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5862-3310","authenticated-orcid":false,"given":"Alexander","family":"Drobyshevsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025092304400556000_2025.09.18.677186v1.1","doi-asserted-by":"publisher","DOI":"10.1097\/00008480-200004000-00004"},{"key":"2025092304400556000_2025.09.18.677186v1.2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2015.00198"},{"key":"2025092304400556000_2025.09.18.677186v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2010.02.002"},{"key":"2025092304400556000_2025.09.18.677186v1.4","first-page":"1037131","article-title":"Hypothermia combined with neuroprotective adjuvants shortens the duration of hospitalization in infants with hypoxic ischemic encephalopathy: Meta-analysis","volume":"13","year":"2022","journal-title":"Front Pharmacol"},{"issue":"9","key":"2025092304400556000_2025.09.18.677186v1.5","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1113\/EP092045","article-title":"Interference with glutamate antiporter system x(c) (-) enables post-hypoxic longterm potentiation in hippocampus","volume":"109","year":"2024","journal-title":"Exp Physiol"},{"key":"2025092304400556000_2025.09.18.677186v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2020.113575"},{"issue":"9","key":"2025092304400556000_2025.09.18.677186v1.7","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1001\/jamapediatrics.2017.1689","article-title":"Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy: Advances in Diagnosis and Treatment","volume":"171","year":"2017","journal-title":"JAMA Pediatr"},{"key":"2025092304400556000_2025.09.18.677186v1.8","doi-asserted-by":"crossref","unstructured":"Zhu, C. , X. 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