Genetic diversity drives extreme responses to traumatic brain injury and post-traumatic epilepsy
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Le résumé fourni par la source
Traumatic brain injury (TBI) is a complex and heterogeneous condition that can cause wide-spectral neurological sequelae such as behavioral deficits, sleep abnormalities, and post-traumatic epilepsy (PTE). However, understanding the interaction of TBI phenome is challenging because few animal models can recapitulate the heterogeneity of TBI outcomes. We leveraged the genetically diverse recombinant inbred Collaborative Cross (CC) mice panel and systematically characterized TBI-related outcomes in males from 12 strains of CC and the reference C57BL/6J mice. We identified unprecedented extreme responses in multiple clinically relevant traits across CC strains, including weight change, mortality, locomotor activity, cognition, and sleep. Notably, we identified CC031 mouse strain as the first rodent model of PTE that exhibit frequent and progressive post-traumatic seizures after moderate TBI induced by lateral fluid percussion. Multivariate analysis pinpointed novel biological interactions and three principal components across TBI-related modalities. Estimate of the proportion of TBI phenotypic variability attributable to strain revealed large range of heritability, including >70% heritability of open arm entry time of elevated plus maze. Our work provides novel resources and models that can facilitate genetic mapping and the understanding of the pathobiology of TBI and PTE.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Genetic diversity drives extreme responses to traumatic brain injury and post-traumatic epilepsy
- Date Crossref
- 01/04/2024
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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The Ohio State University Department of Neuroscience pays non établi dans la noticeUniversité ou école supérieure
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Institute for Behavioral Medicine pays non établi dans la noticeStructure de recherche
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University of North Carolina at Chapel Hill Department of Genetics pays non établi dans la noticeUniversité ou école supérieure
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UNC Lineberger Comprehensive Cancer Center pays non établi dans la noticeÉtablissement de santé
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College of Veterinary Medicine pays non établi dans la noticeUniversité ou école supérieure
Department of Neuroscience — The Ohio State University, Institute for Behavioral Medicine et Department of Genetics — University of North Carolina at Chapel Hill, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.