Interactions of Generalized Epilepsy with Repetitive Mild Traumatic Brain Injury on Somatosensory Function
Abstract number :
1.005
Submission category :
1. Basic Mechanisms / 1A. Epileptogenesis of acquired epilepsies
Year :
2024
Submission ID :
911
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Krista Paffenroth, BS – Vanderbilt University
Tonia Rex, PhD – Vanderbilt University
Fiona Harrison, MD – Vanderbilt University
Presenting Author: Martin Gallagher, MD, PhD – Vanderbilt University / Dept Veteran's Affairs
Rationale: Generalized epilepsy and mild traumatic brain injury (mTBI) are linked to disruptions in thalamocortical network physiology and are increasingly associated with sensory processing difficulties. It is possible that thalamocortical network dysfunction impairs sensory processing, making epilepsy patients more susceptible to sensory processing changes after an mTBI. Repeated mTBI (RmTBI), where a subsequent mTBI occurs before full recovery from the initial injury, has been linked to a higher incidence of chronic symptoms compared to a single mTBI. Thus, our aim was to investigate the effects of RmTBI on somatosensory function in a genetic mouse model of generalized epilepsy.
Methods: We used adult C57BL/6J mice of both sexes that heterozygously express a human generalized epilepsy gene mutation in the GABAA receptor α1 subunit (Gabra1+/A322D) as well as their wild type littermates. Anesthetized mice received either a sham exposure (control) or an overpressure blast mTBI administered twice, spaced 45 minutes apart. Each mTBI consisted of three 40 psi blasts to the dorsal skull within one second, simulating a pressure wave from surfaces or mines detonated in series. We used the somatosensory behavioral tests, whisker stimulation, forepaw von Frey filament response, forepaw adhesive removal, and texture-based object preference Behavioral tests were performed before RmTBI and at four hours, one day, seven days, and 28 days after RmTBI. Ordinal and linear regression models were used to analyze the longitudinal effects of RmTBI, epilepsy genotype, and sex on somatosensory behavioral response before and after sham/RmTBI.
Results: Female epilepsy mice exhibited a lower baseline median whisker response probability (0.83, Q1-Q3 0.67-0.84) compared to wild-type mice (1.00, Q1-Q3 0.83-1.00, P=0.02). After RmTBI, male wild-type mice showed an increased median whisker response probability at four hours (Sham: 0.50, Q1-Q3 0.58-0.83; RmTBI: 0.83, Q1-Q3 0.75-0.92, P=0.009) and seven days (Sham: 0.67, Q1-Q3 0.42-0.92; RmTBI: 1.00, Q1-Q3 0.83-1.00, P=0.01). No changes were observed in female or mutant male mice. Conversely, RmTBI decreased von Frey forepaw nuisance sensitivity in male wild-type mice, as indicated by significant increases in the mean filament size at four hours (Sham: 2.7±0.28; RmTBI: 3.0±0.36, P=0.03) and seven days (Sham: 2.5±0.15; RmTBI: 2.9±0.35, P=0.008). Additionally, RmTBI increased the novel texture preference index in female wild-type mice at seven days (Sham: 31±23%; RmTBI: 53±23%, P=0.004) and 28 days (Sham: 29±22%; RmTBI: 61±19%, P=0.009), and in male mice at seven days (Sham: 22±22%; RmTBI: 57±25%, P=0.004).
Conclusions: RmTBI induces genotype- and sex-specific alterations in somatosensory function, with the most prolonged changes observed in female wild-type mice. The reduced sensitivity of generalized epilepsy mice to RmTBI-associated changes in somatosensory function may suggest the presence of compensatory mechanisms within their thalamocortical networks.
Funding: VA I01 BX005316, Sever Family Fund
Basic Mechanisms