Experimental studies have shown that ligands of the 18 kDa translocator protein can reduce neuronal damage induced by traumatic brain injury by protecting mitochondria and preventing metabolic crisis. Etifoxine, an anxiolytic drug and 18 kDa translocator protein ligand, has shown beneficial effects in the models of peripheral nerve neuropathy. The present study investigates the potential effect of etifoxine as a neuroprotective agent in traumatic brain injury (TBI). For this purpose, the effect of etifoxine on lesion volume and modified neurological severity score at 4 weeks was tested in Sprague–Dawley adult male rats submitted to cortical impact contusion. Effects of etifoxine treatment on neuronal survival and apoptosis were also assessed by immune stains in the perilesional area. Etifoxine induced a significant reduction in the lesion volume compared to nontreated animals in a dose-dependent fashion with a similar effect on neurological outcome at four weeks that correlated with enhanced neuron survival and reduced apoptotic activity. These results are consistent with the neuroprotective effect of etifoxine in TBI that may justify further translational research.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in young adults, characterized by primary and secondary injury. Primary injury is the immediate mechanical damage, while secondary injury results from delayed neuronal death, often linked to mitochondrial damage accumulation. Hyperbaric oxygen therapy (HBOT) has been proposed as a potential treatment for modulating secondary post-traumatic neuronal death. However, the specific molecular mechanism by which HBOT modulates secondary brain damage through mitochondrial protection remains unclear. Spatial learning, reference memory, and motor performance were measured in rats before and after Controlled Cortical Impact (CCI) injury. The HBOT (2.5 ATA) was performed 4 h following the CCI and twice daily (12 h intervals) for four consecutive days. Mitochondrial functions were assessed via high-resolution respirometry on day 5 following CCI. Moreover, IHC was performed at the end of the experiment to evaluate cortical apoptosis, neuronal survival, and glial activation. The current result indicates that HBOT exhibits a multi-level neuroprotective effect. Thus, we found that HBOT prevents cortical neuronal loss, reduces the apoptosis marker (cleaved-Caspase3), and modulates glial cell proliferation. Furthermore, HBO treatment prevents the reduction in mitochondrial respiration, including non-phosphorylation state, oxidative phosphorylation, and electron transfer capacity. Additionally, a superior motor and spatial learning performance level was observed in the CCI group treated with HBO compared to the CCI group. In conclusion, our findings demonstrate that HBOT during the critical period following the TBI improves cognitive and motor damage via regulating glial proliferation apoptosis and protecting mitochondrial function, consequently preventing cortex neuronal loss.

Two hundred and sixty-three consecutive head-injured patients aged over 65 years, admitted to a neurosurgical service, are reported. In contrast to younger age group the main cause was falls concomitant with a high rate of cardiovascular pre-existing disorders. The distribution of causes and grim results justify, in our opinion, regarding head injury in the elderly as a distinct entity requiring special surgical, medical, organizational and ethical considerations.

Traumatic brain injury (TBI) remains a leading cause of mortality and chronic disability. Among therapeutic agents investigated, simvastatin has emerged as a potential therapeutic opportunity for management of TBI although its mechanism of action has not been yet elucidated. Recent advance in 3D molecular docking simulations has suggested a possible interaction between simvastatin and the 18 ​kDa translocator protein (TSPO). Accumulating evidence suggest that The TSPO may play a pivotal role following TBI with TSPO ligands enhancing mitochondrial function and survival. Here, we examined the neuroprotective effects of simvastatin on cognitive and locomotor functions, histopathological outcome, and mitochondrial respiration following TBI in rats. In addition, molecular docking/interactions of simvastatin with TSPO were simulated. The current result show that simvastatin treatment significantly improved cognitive recovery in Morris water maze, motor performance in rotarod test, and neuronal density in the lesion area and hippocampus compared with untreated TBI groups. Importantly, these effects were attenuated by PK11195 pretreatment. Moreover, molecular docking simulations revealed that simvastatin exhibits a high binding affinity to TSPO, suggesting that its beneficial role could be the result of TSPO modulation. Furthermore, simvastatin treatment restored mitochondrial respiration by enhancing oxygen consumption rates across various respiratory states. In contrast, comparative analyses revealed that PK11195 attenuated simvastatin-induced respiratory enhancement, providing strong evidence for a TSPO-mediated mechanism of action of simvastatin. In conclusion, the current result highlights simvastatin's therapeutic potential in mitigating mitochondrial dysfunction and promoting neuroprotection effects following TBI. Our findings underscore mitochondrial protection as an important therapeutic target in TBI.