Sex Differences in Electrographic Activity and Neuronal Injury Patterns in the DFP Model of Status Epilepticus
Abstract number :
2.219
Submission category :
7. Anti-seizure Medications / 7A. Animal Studies
Year :
2022
Submission ID :
2204408
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:24 AM
Authors :
xin wu, MD – Texas A&M University Health Science Center College of Medicine; Tanveer Singh, PhD – Department of Neuroscience and Experimental Therapeutics – Texas A&M University College of Medicine; Sreevidhya Ramakrishnan, PhD – Department of Neuroscience and Experimental Therapeutics – Texas A&M University College of Medicine; Doodipala Samba Reddy, PhD – Department of Neuroscience and Experimental Therapeutics – Texas A&M University College of Medicine
Rationale: Sex differences in epilepsy are abundant, existing across the gamut of seizure disorders. The susceptibility to excitability episodes and seizure susceptibility are higher in men than women. Although the precise mechanisms remain unclear, differences in steroid hormones, regional morphology and neural circuits in male and female brain may contribute to differential vulnerability to epileptogenic outcomes. Exposure to organophosphates (OP), such as diisopropylfluorophosphate (DFP), can lead to seizures, status epilepticus (SE), and brain injury. Current antidotes for OP poisoning do not account for the varied neuronal frameworks between male and female brains. In this study, we compared the extent of electrographic seizure activity and neuronal degeneration between male and female rats after DFP exposure-induced SE.
Methods: DFP-induced SE and seizure activity were monitored by 24 h EEG recording after agent exposure and the extent of brain injury was determined by FJB(+) staining and stereological counting.
Results: There are striking sex differences in EEG seizure activity patterns after DFP exposure and in response to midazolam treatment. The number of FJB(+) injured cells significantly increased in the hippocampus and other regions in DFP-exposed both sexes groups. However, there were significant increases in injured cells and necrotic cell density in the hippocampal dentate gyrus, and dentate hilus subfields of female group compared to the male group. Extensive neuronal injury was evident in the somatosensory cortex in male group.
Conclusions: These results demonstrate striking sex differences in DFP-induced seizure activity and neuronal damage patterns, and this has potential implications in designing sex-specific, neuroprotective strategies in epilepsy and SE.
Funding: NIH grant #U01-NS117278 (to D.S.R.)
Anti-seizure Medications