Antioxidant, OPC-14117, attenuates edema formation, and subsequent tissue damage following cortical contusion in rats.
Oxygen free radicals contribute to various kinds of tissue injury processes within the central nervous system. It has been suggested that inhibition of free radical formation has the potential to attenuate secondary neural tissue damage involving ischemia or trauma, and antioxidant therapy may offer a promising approach. In the present study, employing a cortical contusion model in the rat, contusion-induced neural damage, was evaluated by investigating edema formation, behavioral activities and histological changes. The effects of the superoxide radical scavenger, OPC-14117, were also tested to determine how free radicals may contribute to such neural damage. The results demonstrated that cerebral contusion induces a progressive decrease in tissue specific gravity representing edema formation, and behavioral deficits in the Morris water maze test and habituation of exploratory activity. Histological examinations revealed necrotic cavity formation in the cortex and selective neuronal death of the hippocampal CA3 region. These changes were significantly attenuated by OPC-14117, which was administered as a single dose immediately following trauma induction. The above results indicate that oxygen free radicals are involved in contusion-induced edema formation, subsequent tissue damage and cognitive deficits. The superoxide radical scavenger, OPC-14117, has a powerful therapeutic potential for preventing secondary cell damage following traumatic brain injury.
Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
T
T
Mori
T
T
Kawamata
Y
Y
Katayama
T
T
Maeda
N
N
Aoyama
T
T
Kikuchi
Y
Y
Uwahodo
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001924:Brain Concussion / Q000473:pathology*; D001925:Brain Damage, Chronic / Q000473:pathology*; D001929:Brain Edema / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D002540:Cerebral Cortex / Q000293:injuries* / Q000473:pathology; D007189:Indans / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009336:Necrosis; D009474:Neurons / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D007189:Indans; D010879:Piperazines; C074852:OPC 14117