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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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Concussion susceptibility is mediated by spreading depolarization-induced neurovascular dysfunction
Ellen Parker1,2, Refat Aboghazleh1,3, Griffin Mumby1
1Department of Medical Neuroscience, Dalhousie University, Faculty of Medicine, Halifax, NS, Canada.
Brain : a Journal of Neurology
|December 20, 2021
Summary
Repetitive mild traumatic brain injury can cause severe complications. Early detection of blood-brain barrier dysfunction and TGFβ signaling may predict outcomes and guide treatment for traumatic brain injury.
Area of Science:
- Neuroscience
- Traumatology
- Biomarkers
Background:
- Mechanisms of mild traumatic brain injury (mTBI) complications are poorly understood.
- This limits development of diagnostic/prognostic biomarkers and treatments.
- Early electrophysiological and neurovascular alterations following repetitive mTBI require characterization.
Purpose of the Study:
- Characterize early electrophysiological and neurovascular alterations after repetitive mTBI.
- Identify new targets for diagnosis and treatment of severe post-impact complications.
- Investigate the role of cortical spreading depolarizations (CSDs) and TGFβ signaling in mTBI.
Main Methods:
- Combined behavioral, electrophysiological, molecular, and neuroimaging techniques in a rodent model.
- Used dynamic contrast-enhanced MRI in humans to quantify blood-brain barrier (BBB) dysfunction post-sport-related mTBI.
- Administered a selective TGFβ receptor inhibitor in rats.
Main Results:
- Repetitive mTBI susceptible rats showed greater neurological complications, BBB dysfunction, TGFβ signaling, and neuroinflammation.
- CSDs were common post-mTBI and associated with longer recovery; triggering CSDs induced BBB dysfunction in mTBI rats.
- TGFβ receptor inhibition prevented BBB opening and reduced injury complications.
- BBB dysfunction was observed in a subset of human athletes post-concussive mTBI.
Conclusions:
- CSD, BBB dysfunction, and pro-inflammatory TGFβ signaling are linked to severe outcomes in repetitive mTBI.
- Targeting TGFβ signaling may offer a novel diagnostic and therapeutic strategy for mTBI.
- Early identification of susceptible individuals and intervention are crucial for managing mTBI complications.
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