Therapeutic evaluation of etanercept in a model of traumatic brain injury.
Antagonism of tumor necrosis factor-alpha with etanercept has proved to be effective in the treatment of spinal cord injury and centrally endotoxin-induced brain injury. However, etanercept may offer promise as therapy for traumatic brain injury (TBI). In this study, anesthetized rats, immediately after the onset of TBI, were divided into two major groups and given the vehicle solution (1 mL/kg of body weight) or etanercept (5 mg/kg of body weight) intraperitoneally once per 12 h for consecutive 3 days. Etanercept caused attenuation of TBI-induced cerebral ischemia (e.g., increased cellular levels of glutamate and lactate-to-pyruvate ratio), damage (e.g., increased cellular levels of glycerol) and contusion and motor and cognitive function deficits. TBI-induced neuronal apoptosis (e.g., increased numbers of terminal deoxynucleotidyl transferase αUTP nick-end labeling and neuronal-specific nuclear protein double-positive cells), glial apoptosis (e.g., increased numbers of terminal deoxynucleotidyl transferase αUTP nick-end labeling and glial fibrillary acidic protein double-positive cells), astrocytic (e.g., increased numbers of glial fibrillary acidic protein positive cells) and microglial (e.g., increased numbers of ionized calcium-binding adapter molecule 1-positive cells) activation and activated inflammation (e.g., increased levels of tumor necrosis factor-alpha, interleukin-1β and interleukin-6) were all significantly reduced by etanercept treatment. These findings suggest that etanercept may improve outcomes of TBI by penetrating into the cerebrospinal fluid in rats.
Chio
Chung-Ching
CC
Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan.
Lin
Jia-Wei
JW
Chang
Ming-Wen
MW
Wang
Che-Chuan
CC
Kuo
Jinn-Rung
JR
Yang
Chung-Zhing
CZ
Chang
Ching-Ping
CP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001930:Brain Injuries / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D000068800:Etanercept; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007074:Immunoglobulin G / Q000627:therapeutic use*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept