Effect of etanercept and lithium chloride on preventing secondary tissue damage in rats with experimental diffuse severe brain injury

Abstract

OBJECTIVE: Studies in animals have provided key evidence that antagonizing TNF-alpha is a viable therapeutic strategy for diffuse severe brain injury. This study is planned to prevent post-traumatic secondary tissue damages in rat diffuse severe brain injury model, which is induced by alone or combined administration of Etanercept and lithium chloride (LiCl).

MATERIALS AND METHODS: Male SpragueDawley rats were used in the current study. Rats were divided into 5 groups. Trauma was not induced and treatment was not applied to rats of Sham group. For rats of Trauma+Saline group, saline 0.9% was administered via intraperitoneal (i.p.) route at dose of 1 mg/100 g body weight 1 hour after trauma. For rats of Trauma+Etanercept group, Etanercept was administered via i.p. route at dose of 5 mg/kg body weight 1 hour after trauma. For rats of Trauma+LiCl group, LiCl was administered via i.p. route at dose of 50 mg/kg body weight 1 hour after trauma. For rats of Etanercept+LiCl group, Etanercept and LiCl were administered via i.p. route at dose of 5 mg/kg body weight and 50 mg/kg body weight, respectively, 1 hour after trauma. Serum glial fibrillary acidic protein (GFAP) and Tau levels were analyzed with ELISA. For analyses H&E, TUNEL, GFAP and TNF-alpha staining methods were used.

RESULTS: We demonstrate that Etanercept treatment reduced the TBI-induced brain tissues alteration, reduced the expression of TNF-alpha and improve edema and axonal swelling. We observed a significant decrease in TNF-alpha and GFAP positivity after LiCl was administered.

CONCLUSIONS: The findings obtained in this study suggest that the combination therapy with Etanercept and LiCl decreased neuronal degeneration and alleviated secondary tissue damage in post-traumatic period.