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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 |