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Palzur 2021 Int J Mol Sci

From Bioblast
Publications in the MiPMap
Palzur E, Edelman D, Sakas R, Soustiel JF (2021) Etifoxine restores mitochondrial oxidative phosphorylation and improves cognitive recovery following traumatic brain injury. Int J Mol Sci 22:12881. doi: 10.3390/ijms222312881

Β» PMID: 34884686 Open Access

Palzur E, Edelman D, Sakas R, Soustiel JF (2021) Int J Mol Sci

Abstract: The opening of the mitochondrial permeability transition pore (mtPTP) has emerged as a pivotal event following traumatic brain injury (TBI). Evidence showing the impact of the translocator protein (TSPO) over mtPTP activity has prompted several studies exploring the effect of TSPO ligands, including etifoxine, on the outcome of traumatic brain injury. Mitochondrial respiration was assessed by respirometry in isolated rat brain mitochondria (RBmt) by measurements of oxidative phosphorylation capacity (OXPHOS). The addition of calcium to RBmt was used to induce mitochondrial injury and resulted in significant OXPHOS reduction that could be reversed by preincubation of RBmt 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.

β€’ Bioblast editor: Gnaiger E

Labels: MiParea: Respiration, Pharmacology;toxicology 

Organism: Rat  Tissue;cell: Nervous system  Preparation: Isolated mitochondria 

Regulation: Calcium  Coupling state: LEAK, OXPHOS  Pathway: N, S, ROX  HRR: Oxygraph-2k