Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/33978
Title: Inherent Susceptibility to Acquired Epilepsy in Selectively Bred Rats Influences the Acute Response to Traumatic Brain Injury.
Austin Authors: Leung, Wai Lam;Dill, Larissa K;Perucca, Piero ;O'Brien, Terence J;Casillas-Espinosa, Pablo M;Semple, Bridgette D
Affiliation: Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.;Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.;The Perron Institute for Neurological and Translational Science, Nedlands, Western Australia, Australia.
Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.
Department of Neurology, The Royal Melbourne Hospital, Parkville, Victoria, Australia.;Department of Medicine (Royal Melbourne Hospital), The University of Melbourne, Parkville, Victoria, Australia.
Epilepsy Research Centre
Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.;Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.;Department of Medicine (Royal Melbourne Hospital), The University of Melbourne, Parkville, Victoria, Australia.
Issue Date: Oct-2023
Date: 2023
Publication information: Journal of Neurotrauma 2023-10; 40(19-20)
Abstract: Traumatic brain injury (TBI) often causes seizures associated with a neuroinflammatory response and neurodegeneration. TBI responses may be influenced by differences between individuals at a genetic level, yet this concept remains understudied. Here, we asked whether inherent differences in one's vulnerability to acquired epilepsy would determine acute physiological and neuroinflammatory responses acutely after experimental TBI, by comparing selectively bred "seizure-prone" (FAST) rats with "seizure-resistant" (SLOW) rats, as well as control parental strains (Long Evans and Wistar rats). Eleven-week-old male rats received a moderate-to-severe lateral fluid percussion injury (LFPI) or sham surgery. Rats were assessed for acute injury indicators and neuromotor performance, and blood was serially collected. At 7 days post-injury, brains were collected for quantification of tissue atrophy by cresyl violet (CV) histology, and immunofluorescent staining of activated inflammatory cells. FAST rats showed an exacerbated physiological response acutely post-injury, with a 100% seizure rate and mortality within 24 h. Conversely, SLOW rats showed no acute seizures and a more rapid neuromotor recovery compared with controls. Brains from SLOW rats also showed only modest immunoreactivity for microglia/macrophages and astrocytes in the injured hemisphere compared with controls. Further, group differences were apparent between the control strains, with greater neuromotor deficits observed in Long Evans rats compared with Wistars post-TBI. Brain-injured Long Evans rats also showed the most pronounced inflammatory response to TBI across multiple brain regions, whereas Wistar rats showed the greatest extent of regional brain atrophy. These findings indicate that differential genetic predisposition to develop acquired epilepsy (i.e., FAST vs. SLOW rat strains) determines acute responses after experimental TBI. Differences in the neuropathological response to TBI between commonly used control rat strains is also a novel finding, and an important consideration for future study design. Our results support further investigation into whether genetic predisposition to acute seizures predicts the chronic outcomes after TBI, including the development of post-traumatic epilepsy.
URI: https://ahro.austin.org.au/austinjspui/handle/1/33978
DOI: 10.1089/neu.2022.0463
ORCID: 
Journal: Journal of neurotrauma
Start page: 2174
End page: 2192
PubMed URL: 37221897
ISSN: 1557-9042
Type: Journal Article
Subjects: FAST and SLOW rats
gliosis
inflammation
seizures
traumatic brain injury
Brain Injuries, Traumatic/complications
Epilepsy/etiology
Seizures/etiology
Brain Injuries/complications
Appears in Collections:Journal articles

Show full item record

Page view(s)

28
checked on Mar 4, 2024

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.