Comparative Profile of Refractory Status Epilepticus Models Following Exposure of Three Distinct Cholinergic Agents
Abstract number :
3.063
Submission category :
1. Basic Mechanisms / 1E. Models
Year :
2021
Submission ID :
1825743
Source :
www.aesnet.org
Presentation date :
12/9/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:50 AM
Authors :
Xin Wu, MD - Texas A&M University Health Science Center College of Medicine; Marcus Zaayman, MD – Department of Neuroscience and Experimental Therapeutics – Texas A&M University Health Science Center College of Medicine; Ramkumar Kuruba, PhD – Department of Neuroscience and Experimental Therapeutics – Texas A&M University Health Science Center College of Medicine; D. Samba Reddy, PhD – Department of Neuroscience and Experimental Therapeutics – Texas A&M University Health Science Center College of Medicine
Rationale: Status epilepticus (SE) is a medical emergency condition with continuous seizure activity that lasts at least 5 min and causes profound neuronal damage, morbidity, or death. SE incidents can arise spontaneously, but mostly are elicited by seizurogenic triggers. Chemoconvulsants such as the muscarinic agonist pilocarpine and organophosphates (OP) such as the pesticide DFP and the nerve agent soman can induce persistent seizures and SE. They share a common feature of cholinergic crisis that transitions into a state of refractory SE, but their comparative profiles remain unclear. In this study, we evaluated the comparative convulsant profile of pilocarpine, DFP, and soman to produce refractory SE and brain damage in rats.
Methods: Behavioral and electrographic seizures were monitored after agent exposure and the extent of brain injury was determined by histological markers of neuronal injury and degeneration.
Results: Seizures were elicited at slower pace after pilocarpine as compared to DFP or soman, which caused rapid onset of spiking within 8-10 min that swiftly developed into persistent SE lasting for hours. Time-course of SE activity after DFP was comparable to that after soman, a potent neurotoxic chemical agent. Benzodiazepine controlled pilocarpine-induced SE, but it was ineffective in reducing DFP- and soman-induced SE. All three agents produced marked neuronal injury and neurodegeneration in the brain.
Conclusions: These results reveal distinct convulsant and neuronal injury patterns following exposure to cholinergic agonists, OP pesticides, and nerve agents. A battery of SE models is essential to identify novel anticonvulsant therapies for the management of refractory SE.
Funding: Please list any funding that was received in support of this abstract.: NIH U01-NS083460, U01-NS117209, and U01-NS117278 (to D.S.R.).
Basic Mechanisms