MMP-9 Inhibitor SB-3CT Attenuates Behavioral Impairments and Hippocampal Loss after Traumatic Brain Injury in Rat

Abstract

The aim of this study was to evaluate the potential efficacy of SB-3CT, a matrix metallopeptidase 9 inhibitor, on behavioral and histological outcomes after traumatic brain injury (TBI) in rats. Adult male Sprague-Dawley rats were randomly divided into three groups (n=15/group): TBI with SB-3CT treatment, TBI with saline, and sham injury. The TBI model was induced by a fluid percussion TBI device. SB-3CT (50 mg/kg in 10% dimethyl sulfoxide) was administered intraperitoneally at 30 min, 6 h, and 12 h after the TBI. Motor function (beam-balance/beam-walk tests) and spatial learning/memory (Morris water maze) were assessed on post-operative Days 1-5 and 11-15, respectively. Fluoro-Jade staining, immunofluorescence, and cresyl violet-staining were carried out for histopathological evaluation at 24 h, 72 h, and 15 days after TBI, respectively. It was shown that TBI can result in significant behavioral deficit induced by acute neurodegeneration, increased expression of cleaved caspase-3, and long-term neuronal loss. SB-3CT intervention via the current regime provides robust behavioral protection and hippocampal neurons preservation from the deleterious effects of TBI. Hence, the efficacy of SB-3CT on TBI prognosis could be ascertained. It is believed that the current study adds to the growing literature in identifying SB-3CT as a potential therapy for human brain injury.