Aquaporin-4 Reduces Post-Traumatic Seizure Susceptibility by Promoting Astrocytic Glial Scar Formation in Mice
| Autor: | Daniel C. Lu, Jinghua Yao, Zsolt Zador, Farbod Fazlollahi, Geoffrey T. Manley |
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| Rok vydání: | 2021 |
| Předmět: |
Traumatic brain injury
Ischemia Epileptogenesis Glial scar Cicatrix Mice Post-traumatic seizure Epilepsy Seizures Brain Injuries Traumatic medicine Animals Aquaporin 4 Mice Knockout business.industry Original Articles medicine.disease medicine.anatomical_structure Astrocytes Anesthesia Neurology (clinical) medicine.symptom business Neuroglia Astrocyte |
| Zdroj: | J Neurotrauma |
| ISSN: | 1557-9042 0897-7151 |
| Popis: | Seizures are important neurological complications after traumatic brain injury (TBI) and are reported for up to 50% of patients with TBI. Despite several studies, no drug strategy has been able to alter the biological events leading to epileptogenesis. The glial water channel, aquaporin-4 (AQP4), was shown to facilitate cytotoxic cell swelling in ischemia and glial scar formation after stab wound injury. In this study, we examined post-traumatic seizure susceptibility of AQP4-deficient mice (AQP4(–/–)) after injection of pentylenetetrazole (PTZ) 1 month after controlled cortical impact (CCI) and compared them to wild-type sham injury controls. After PTZ injection, AQP4(–/–) mice demonstrated dramatically shortened seizure latency (120 ± 40 vs. 300 ± 70 sec; p 0.05) and severity of seizures evoked by PTZ (grade 4.0 ± 0.5 vs. 3.81 ± 0.30; p > 0.05) compared to wild-type counterparts. Immunohistochemical analysis demonstrated decreased immunostaining of microglia to levels comparable to wild-type (12 ± 2 vs. 11 ± 4 cells/hpf, respectively; p > 0.05). Taken together, these results suggest a protective role of AQP4 in post-traumatic seizure susceptibility by promoting astrogliosis, formation of a glial scar, and preventing microgliosis. |
| Databáze: | OpenAIRE |
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