Ifenprodil Improves Long-Term Neurologic Deficits Through Antagonizing Glutamate-Induced Excitotoxicity After Experimental Subarachnoid Hemorrhage
| العنوان: | Ifenprodil Improves Long-Term Neurologic Deficits Through Antagonizing Glutamate-Induced Excitotoxicity After Experimental Subarachnoid Hemorrhage |
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| المؤلفون: | Hong-Bin Wang, Qingbin Ni, Qiong-Jie Mi, Jing-yi Sun, Shi-jun Zhao, Zong-yong Zhang, Ming-feng Yang, Ya-jun Hou, Hui Yuan, Baoliang Sun |
| المصدر: | Translational Stroke Research. 12:1067-1080 |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| تدمد: | 1868-601X 1868-4483 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3c966a0bae12f35ac3b8a720b20656e6Test https://doi.org/10.1007/s12975-021-00906-4Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....3c966a0bae12f35ac3b8a720b20656e6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1868601X 18684483 |
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