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Malignant astrocyte swelling and impaired glutamate clearance drive the expansion of injurious spreading depolarization foci
- Publication Year :
- 2022
-
Abstract
- Spreading depolarizations (SDs) indicate injury progression and predict worse clinical outcome in acute brain injury. We demonstrate in rodents that acute brain swelling upon cerebral ischemia impairs astroglial glutamate clearance and increases the tissue area invaded by SD. The cytotoxic extracellular glutamate accumulation (>15 µM) predisposes an extensive bulk of tissue (4–5 mm2) for a yet undescribed simultaneous depolarization (SiD). We confirm in rat brain slices exposed to osmotic stress that SiD is the pathological expansion of prior punctual SD foci (0.5–1 mm2), is associated with astrocyte swelling, and triggers oncotic neuron death. The blockade of astrocytic aquaporin-4 channels and Na+/K+/Cl− co-transporters, or volume-regulated anion channels mitigated slice edema, extracellular glutamate accumulation (
- Subjects :
- Oncotic pressure
Pathology
medicine.medical_specialty
Sodium-Potassium-Chloride Symporters
Ischemia
Glutamic Acid
Brain Edema
Cerebral edema
Osmotherapy
Internal medicine
Edema
medicine
Brain swelling
Animals
business.industry
Chemistry
Glutamate receptor
Depolarization
03.01. Általános orvostudomány
medicine.disease
Astrocyte swelling
Rats
Cortex (botany)
Endocrinology
medicine.anatomical_structure
Neurology
Astrocytes
Brain Injuries
Neurology (clinical)
medicine.symptom
Cardiology and Cardiovascular Medicine
business
Neuron death
Astrocyte
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....812d76ef2539a557dfd8c935ebadd2e8