Brain Disorders (Dec 2022)
The effect of Riluzole on neurological outcomes, blood-brain barrier, brain water and neuroinflammation in traumatic brain injury
Abstract
Background: Riluzole (RLZ) is a potent anticonvulsant drug that reveals neuroprotective effects on neurological disease by inhibiting the release of glutamate and increasing its uptake. This study aims to investigate the potential neuroprotective effects of Riluzole in a rat model with acute severe traumatic brain injury (TBI). Materials and Methods: In this study, seven groups of male Wistar rats were investigated including Sham, Intact, TBI, Saline (TBI + intraperitoneal (i.p) injection of normal saline), TBI + i.p injection of Riluzole in 2,4 and 8 mg/kg doses (RLZ 2, RLZ 4 and RLZ 8 groups), induction of severe diffuse TBI performed by weight dropping Marmarou model, and evaluation of short-term neurological deficits by using veterinary coma scale (VCS), beam-balance and beam-walk tasks. Histopathological changes in neural tissue were evaluated by using hematoxylin and eosin staining and light microscopy. Evaluation of blood-brain barrier (BBB) permeability was performed by using the Evans Blue method 6 h after traumatization. Brain water content assessment was performed by using the wet-dry method and the level of IL-1β and IL-10 was determined by using an enzyme-linked immunosorbent assay (ELISA). Results: Treatment with Riluzole improves neurological function, VCS score, and vestibulomotor function, reduces pathological changes of neural tissue, brain edema, and level of IL-1β, and increases IL-10 concentration in CSF compared to the saline group (p < 0.0001). Treatment with 4 and 8 mg/kg of Riluzole reveals a significant therapeutic effect on consequences of TBI. This effect was enhanced by an increase in the dose of Riluzole from 4 to 8 mg/kg, but no significant changes were seen after administration of 2 mg/kg of Riluzole. Conclusion: Riluzole can reduce the first and second phase of TBI damage by lowering inflammation, brain edema, histopathological destruction, BBB permeability, level of IL- 1β, and increasing IL-10 in CSF; it is highly suggested to use Riluzole in further studies and human trials, and also to consider it as a therapeutic compound in the treatment of traumatic brain injury.
