1. Aquaporin-4 Reduces Post-Traumatic Seizure Susceptibility by Promoting Astrocytic Glial Scar Formation in Mice
- Author
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Lu, Daniel C, Zador, Zsolt, Yao, Jinghua, Fazlollahi, Farbod, and Manley, Geoffrey T
- Subjects
Traumatic Head and Spine Injury ,Brain Disorders ,Neurosciences ,Neurodegenerative ,Traumatic Brain Injury (TBI) ,Physical Injury - Accidents and Adverse Effects ,Epilepsy ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,Animals ,Aquaporin 4 ,Astrocytes ,Brain Injuries ,Traumatic ,Cicatrix ,Mice ,Mice ,Knockout ,Neuroglia ,Seizures ,aquaporin ,astrocyte ,glial scar ,seizure epilepsy ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
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.
- Published
- 2021