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Eur Rev Med Pharmacol Sci ; 18(1): 10-27, 2014.
Article in English | MEDLINE | ID: mdl-24452937

ABSTRACT

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.


Subject(s)
Brain Injuries/drug therapy , Immunoglobulin G/therapeutic use , Lithium Chloride/therapeutic use , Neuroprotective Agents/therapeutic use , Receptors, Tumor Necrosis Factor/therapeutic use , Animals , Apoptosis/drug effects , Astrocytes/drug effects , Astrocytes/metabolism , Brain/drug effects , Brain/metabolism , Brain/pathology , Brain Injuries/metabolism , Brain Injuries/pathology , Disease Models, Animal , Drug Therapy, Combination , Etanercept , Glial Fibrillary Acidic Protein/blood , Glial Fibrillary Acidic Protein/metabolism , Immunoglobulin G/pharmacology , Lithium Chloride/pharmacology , Male , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Neuroprotective Agents/pharmacology , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/metabolism , tau Proteins/blood
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