Etifoxine Restores Mitochondrial Oxidative Phosphorylation and Improves Cognitive Recovery Following Traumatic Brain Injury.
etifoxine
mitochondria
mitochondrial permeability transition pore
translocator protein
traumatic brain injury
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
28 Nov 2021
28 Nov 2021
Historique:
received:
31
10
2021
revised:
22
11
2021
accepted:
23
11
2021
entrez:
10
12
2021
pubmed:
11
12
2021
medline:
7
1
2022
Statut:
epublish
Résumé
The opening of the mitochondrial permeability transition pore (mPTP) has emerged as a pivotal event following traumatic brain injury (TBI). Evidence showing the impact of the translocator protein (TSPO) over mPTP activity has prompted several studies exploring the effect of TSPO ligands, including etifoxine, on the outcome of traumatic brain injury (TBI). Mitochondrial respiration was assessed by respirometry in isolated rat brain mitochondria (RBM) by measurements of oxidative phosphorylation capacity (OXPHOS). The addition of calcium to RBM was used to induce mitochondrial injury and resulted in significant OXPHOS reduction that could be reversed by preincubation of RBM with etifoxine. Sensorimotor and cognitive functions were assessed following controlled cortical impact and compared in vehicle and etifoxine-treated animals. There was no difference between the vehicle and etifoxine groups for sensorimotor functions as assessed by rotarod. In contrast, etifoxine resulted in a significant improvement of cognitive functions expressed by faster recovery in Morris water maze testing. The present findings show a significant neuroprotective effect of etifoxine in TBI through restoration of oxidative phosphorylation capacity associated with improved behavioral and cognitive outcomes. Since etifoxine is a registered drug used in common clinical practice, implementation in a phase II study may represent a reasonable step forward.
Identifiants
pubmed: 34884686
pii: ijms222312881
doi: 10.3390/ijms222312881
pmc: PMC8657969
pii:
doi:
Substances chimiques
Anti-Anxiety Agents
0
Oxazines
0
etifoxine
X24X82MX4X
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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