Microglia Are Neuroprotective in Multiple Experimental Seizure Models
Abstract number :
3.068
Submission category :
1. Basic Mechanisms / 1E. Models
Year :
2022
Submission ID :
2204959
Source :
www.aesnet.org
Presentation date :
12/5/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:27 AM
Authors :
Synphane Gibbs, BS – University of Virginia; Kaushik Sharma, PhD – University of virginia; Jordan Benderoth, BS – University Virginia; Ukpong Eyo, PhD – Univeristy of Virginia; Edward Perez-Reyes, PhD – University; Joe Uweru, BS, MS – University of Virginia
Rationale: Microglia, the brain’s resident immune cells, become activated in response to the brain injury caused by seizures. Microglia have been implicated in other neurological disorders because they phagocytize debris and release proinflammatory factors that can lead to more neuronal death. Some studies suggest that seizure phenotypes worsen with pharmacogenetic deletion of microglia in chemo-convulsive seizures. However, the extent to which microglia play roles in seizure disorders broadly remains unclear. The objective of our research is to determine if microglia are neuroprotective in multiple seizure models and if microglia play a role in recovery outcomes after seizures._x000D_
Methods: In our present study we performed chemoconvulsive (using kainic acid or KA), febrile, and electrically-induced seizures on mice and eliminated microglia with PLX3397 (PLX), a csf1r inhibitor. Csf1r function is required for microglial survival. We then assessed brain activity by measuring cFos expression during KA-induced seizures with PLX using TRAP mice. We also assessed seizure recovery after KA-induced seizures with PLX by measuring weight and performing open field tests. _x000D_
Results: We found that seizures in all seizure models (chemo-convulsive, febrile, and electrical) did worsen with the elimination of microglia. Microglial elimination with PLX increased brain activity in the TRAP mice during seizures. Recovery outcomes also did worsen with the elimination of microglia._x000D_
Conclusions: These results suggest that microglia are neuroprotective in multiple experimental seizure models by regulating brain activity and improving seizure recovery outcomes._x000D_
Funding: R01NS119243-01
Basic Mechanisms