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

M.A. Ekici, O. Uysal, H.I. Cikriklar, Z. Özbek, D. Turgut Cosan, C. Baydemir, B. Kazanci, D. Hafizoglu

Neurosurgery Clinic, Ministry of Health, Sevket Yilmaz Research and Training Hospital, Bursa, Turkey. ouysal1971@gmail.com

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• Pharmacology

OBJECTIVE: Studies in animals have provided key evidence that antagonizing TNF-α 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 Sprague-Dawley 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-α staining methods were used.

RESULTS: We demonstrate that Etanercept treatment reduced the TBI-induced brain tissues alteration, reduced the expression of TNF-α and improve edema and axonal swelling. We observed a significant decrease in TNF-α 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.

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