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Updated: Aug 12, 2025

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Combining Imaging and Electrophysiology to Visualize and Record Spreading Depolarizations in Mice
Published on: October 4, 2024
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Spreading depolarization causes reperfusion failure after cerebral ischemia
Anna Törteli1,2, Réka Tóth1,2, Sarah Berger2
1Hungarian Centre of Excellence for Molecular Medicine - University of Szeged, Cerebral Blood Flow and Metabolism Research Group, Szeged, Hungary.
Summary
Spreading depolarization (SD) predicts reperfusion failure and poor outcomes in stroke patients after recanalization. Blocking SD improves reperfusion, highlighting its role in stroke recovery.
Area of Science:
- Neuroscience
- Cerebrovascular Research
- Ischemic Stroke Pathophysiology
Background:
- Reperfusion failure after stroke treatment leads to poor neurological outcomes in many patients.
- Spreading depolarization (SD) is a wave of intense neuronal activity followed by a prolonged suppression of activity, implicated in brain injury.
Purpose of the Study:
- To investigate whether spreading depolarization (SD) predicts reperfusion failure following experimental stroke.
- To assess the impact of SD on neurological deficits and neuronal injury after ischemia/reperfusion.
Main Methods:
- Induced global forebrain ischemia/reperfusion in mice (n=57).
- Visualized SD and cerebral blood flow (CBF) using transcranial optical imaging and laser speckle contrast imaging.
- Administered MK801 to block SD (n=26) and evaluated neurological deficit, CoW anatomy, and neuronal injury 24 hours later.
Main Results:
- SD occurred under a critical perfusion threshold (CBF drop to 21.1±4.6%) and was invariably linked to reperfusion failure (44.4±12.5%).
- Adequate reperfusion (98.9±7.4%) occurred in hemispheres without SD.
- Inadequate circle of Willis (CoW) collaterals, specifically absence of the P1 segment of the posterior cerebral artery, predicted SD occurrence and reperfusion failure.
- SD occurrence correlated with poor neurological function and neuronal necrosis.
Conclusions:
- Spreading depolarization during ischemia impairs subsequent reperfusion and predicts poor neurological outcomes in stroke.
- Inhibiting SD significantly improved reperfusion after experimental stroke.
- Inadequate cerebrovascular collaterals increase the likelihood of SD and subsequent reperfusion failure.
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