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Ifenprodil Improves Long-Term Neurologic Deficits Through Antagonizing Glutamate-Induced Excitotoxicity After Experimental Subarachnoid Hemorrhage
- Source :
- Translational Stroke Research. 12:1067-1080
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Excessive glutamate leading to excitotoxicity worsens brain damage after SAH and contributes to long-term neurological deficits. The drug ifenprodil is a non-competitive antagonist of GluN1-GluN2B N-methyl-d-aspartate (NMDA) receptor, which mediates excitotoxic damage in vitro and in vivo. Here, we show that cerebrospinal fluid (CSF) glutamate level within 48 h was significantly elevated in aSAH patients who later developed poor outcome. In rat SAH model, ifenprodil can improve long-term sensorimotor and spatial learning deficits. Ifenprodil attenuates experimental SAH-induced neuronal death of basal cortex and hippocampal CA1 area, cellular and mitochondrial Ca2+ overload of basal cortex, blood-brain barrier (BBB) damage, and cerebral edema of early brain injury. Using in vitro models, ifenprodil declines the high-concentration glutamate-mediated intracellular Ca2+ increase and cell apoptosis in primary cortical neurons, reduces the high-concentration glutamate-elevated endothelial permeability in human brain microvascular endothelial cell (HBMEC). Altogether, our results suggest ifenprodil improves long-term neurologic deficits through antagonizing glutamate-induced excitotoxicity.
- Subjects :
- 0301 basic medicine
Excitotoxicity
Glutamic Acid
Brain damage
medicine.disease_cause
Receptors, N-Methyl-D-Aspartate
Cerebral edema
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Piperidines
Ifenprodil
Animals
Humans
Medicine
business.industry
General Neuroscience
Glutamate receptor
Human brain
Subarachnoid Hemorrhage
medicine.disease
Rats
030104 developmental biology
medicine.anatomical_structure
chemistry
Blood-Brain Barrier
NMDA receptor
Neurology (clinical)
medicine.symptom
Basal cortex
Cardiology and Cardiovascular Medicine
business
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 1868601X and 18684483
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Translational Stroke Research
- Accession number :
- edsair.doi.dedup.....3c966a0bae12f35ac3b8a720b20656e6