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Contralesional hippocampal spreading depolarization promotes functional recovery after stroke
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Contralesional hippocampal spreading depolarization promotes functional recovery after stroke
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Journal Article
Contralesional hippocampal spreading depolarization promotes functional recovery after stroke
2025
Overview
Ischemic stroke, brain tissue infarction following obstructed cerebral blood flow, leads to long-term neurological deficits and death. While neocortex is a commonly affected region with established preclinical models, less is known about deeper brain strokes, despite having unique neurological outcomes. We induced focal ischemic stroke while simultaneously monitoring neuronal activity in awake behaving Thy1-GCaMP6f mice by delivering and collecting light through bilateral fiberoptic implants. Unilateral hippocampal stroke resulted in atypical wandering behavior coincident with ipsilesional terminal spreading depolarization (sustained increase in GCaMP6f fluorescence). Ischemia induced seizures that propagated to the contralesional hippocampus triggering a transient spreading depolarization, predominantly in females. Hippocampal stroke impaired contextual fear conditioning acquired pre-stroke. Yet, 7 days post-stroke, contextual fear conditioning was only improved in mice with contralesional spreading depolarization. Blunting peri-stroke contralesional spreading depolarization prevented recovery of hippocampus-dependent learning. Together, we show that regionally isolated deleterious and beneficial spreading depolarizations can occur concurrently in the murine brain during acute stroke.
Neural mechanisms underlying deep brain strokes are not fully understood. Here authors demonstrate that spreading depolarizations occur in the intact contralesional hippocampus during unilateral stroke. These spreading depolarizations are more common in female mice and allow preservation of hippocampus-dependent learning.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/35
/ 631/1647
/ 64/60
/ 9/10
/ 9/30
/ Animals
/ Brain
/ Brain Ischemia - physiopathology
/ Cortical Spreading Depression - physiology
/ Fear
/ Female
/ Females
/ Hippocampus - physiopathology
/ Humanities and Social Sciences
/ Ischemia
/ Learning
/ Male
/ Mice
/ Recovery
/ Recovery of Function - physiology
/ Science
/ Seizures
/ Stroke
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