Characterizing Sex Differences in Mitochondrial Dysfunction After Severe Traumatic Brain Injury in Mice.
CNS injury
calcium loading
mitochondrial bioenergetics
time course
Journal
Neurotrauma reports
ISSN: 2689-288X
Titre abrégé: Neurotrauma Rep
Pays: United States
ID NLM: 101773091
Informations de publication
Date de publication:
2023
2023
Historique:
medline:
27
9
2023
pubmed:
27
9
2023
entrez:
27
9
2023
Statut:
epublish
Résumé
Traumatic brain injury (TBI) is caused by an impact or penetrating injury to the head resulting in abnormal brain function. Mitochondrial dysfunction is an important hallmark of TBI and has been thoroughly studied in male rodent models of brain injury, but relatively little is known about these outcomes in females. These studies were designed to examine sex as a biological variable for mitochondria-related outcomes after the severe controlled cortical impact (CCI) mouse model of TBI. Synaptic and non-synaptic mitochondria were isolated from the sham- or CCI-injured cortex as well as the hippocampus ipsilateral to the craniotomy 3, 12, 24, or 48 h post-surgery, and then bioenergetics were measured. Subtle variations were observed in the timeline of mitochondrial dysfunction between sexes. Non-synaptic cortical mitochondria from injured females showed early impairment at 12 h post-CCI compared to mitochondria from injured males at 24 h post-CCI. Contrastingly, in the synaptic fraction, mitochondria from injured males showed early impairment at 12 h post-CCI, whereas mitochondria from injured females showed impairment at 24 h post-CCI. Based on bioenergetic impairments at 24 h post-CCI, synaptic and non-synaptic mitochondrial calcium loading was also measured at this time point. Consistent with bioenergetic data at 24 h, non-synaptic mitochondria from injured males had increased calcium loading compared to uninjured control, but this effect was not observed in females. Finally, histological assessment of cortical tissue sparing in each sex was measured at 7 days post-injury. There was a lack of sex-based differences in cortical tissue sparing after severe CCI. Overall, there were some subtle sex differences in mitochondrial outcomes after CCI, but these findings were not statistically significant. This study highlights the importance of utilizing both sexes when measuring mitochondrial function after severe CCI.
Identifiants
pubmed: 37752924
doi: 10.1089/neur.2023.0046
pii: 10.1089/neur.2023.0046
pmc: PMC10518693
doi:
Types de publication
Journal Article
Langues
eng
Pagination
627-642Subventions
Organisme : BLRD VA
ID : I01 BX003405
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM148326
Pays : United States
Organisme : NINDS NIH HHS
ID : T32 NS077889
Pays : United States
Informations de copyright
© Olivia J. Kalimon et al., 2023; Published by Mary Ann Liebert, Inc.
Déclaration de conflit d'intérêts
No competing financial interests exist.
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