Therapeutic evaluation of etanercept in a model of traumatic brain injury

• Published in: Journal of neurochemistry Vol. 115; no. 4; pp. 921 - 929
• Main Authors: Chio, Chung‐Ching, Lin, Jia‐Wei, Chang, Ming‐Wen, Wang, Che‐Chuan, Kuo, Jinn‐Rung, Yang, Chung‐Zhing, Chang, Ching‐Ping
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2010; Wiley-Blackwell
• Subjects: Adult and adolescent clinical studies; Animals; Antibodies, Monoclonal - therapeutic use; Apoptosis; Biological and medical sciences; Body weight; Brain damage; Brain Injuries - cerebrospinal fluid; Brain Injuries - drug therapy; Brain Injuries - pathology; Cell activation; Cerebrospinal fluid; Cognitive ability; Disease Models, Animal; DNA nucleotidylexotransferase; Drug Evaluation, Preclinical - methods; Etanercept; Glial fibrillary acidic protein; Glutamic acid; Glycerol; Hippocampus - metabolism; Hippocampus - pathology; Immunoglobulin G - therapeutic use; Inflammation; Injuries of the nervous system and the skull. Diseases due to physical agents; Interleukin 1; Interleukin 6; Ischemia; Male; Medical sciences; Neurochemistry; Neuronal-glial interactions; Organic mental disorders. Neuropsychology; Pharmacology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, Tumor Necrosis Factor - therapeutic use; Rodents; Spinal cord injury; Traumas. Diseases due to physical agents; Traumatic brain injury; Tumor necrosis factor-a; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - metabolism; tumor necrosis factor‐alpha; Cognitive disorder; Rat; Neuroglia; Cardiovascular disease; Contusion; apoptosis; Endotoxin; Vascular disease; tumor necrosis factor-alpha; inflammation; Spinal cord trauma; Attenuation; Cerebrovascular disease; Nervous system diseases; etanercept; Cytokine; Rodentia; Pyruvate; traumatic brain injury; Glutamate; Cerebral disorder; Toxin; Lactates; Vertebrata; Mammalia; Treatment; Tumor necrosis factor; Central nervous system disease; Excitatory aminoacid; Neurotransmitter; Brain ischemia; Models; Head trauma; Spinal cord disease
• DOI: 10.1111/j.1471-4159.2010.06969.x
• ISSN: 0022-3042

J. Neurochem. (2010) 115, 921-929. ABSTRACT: 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.