Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 23, Pages -Publisher
MDPI
DOI: 10.3390/ijms222312881
Keywords
mitochondria; traumatic brain injury; mitochondrial permeability transition pore; translocator protein; etifoxine
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The study demonstrates that etifoxine exerts significant neuroprotective effects after traumatic brain injury by restoring mitochondrial function and improving behavioral and cognitive outcomes. This suggests that etifoxine may be a promising candidate for further clinical trials in TBI patients.
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.
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