Effects of antioxidant, OPC-14117, on secondary cellular damage and behavioral deficits following cortical contusion in the rat.
In the present study, we examined the effects of OPC-14117, a superoxide radical scavenger, on the secondary cellular damage and cognitive dysfunction occurring in a rat model of cerebral contusion induced by a controlled cortical impact (CCI). Histological examinations revealed that the contusion necrosis volume reached 13.6+/-5.3 mm(3) in non-treated animals and declined to 1.9+/-0.6 mm(3) in OPC-14117-treated animals (P<0.01). The cell number of the CA3 region was 120.0+/-12.4 cells/mm in the normal controls, 73.6+/-9.9 cells/mm in the non-treated animals, and 111.2+/-10.2 cells/mm in the OPC-14117-treated animals, indicating that CCI-induced selective neuronal cell death in the CA3 region was attenuated by the OPC-14117 administration (P<0.01). The tissue osmolality, as determined with a vapor pressure osmometer, was 314.5+/-15.4 mmol/kg in the normal brain and increased to 426.0+/-20.1 mmol/kg at 12 h following CCI. The increase in tissue osmolality was significantly attenuated by OPC-14117 administration (P<0.01). The OPC-14117 administration also attenuated the CCI-induced cognitive deficits. The OPC-14117-treated animals showed a tendency to improve on the Morris water maze performance test. The impairment of the habituation of exploratory activity elicited by CCI was significantly attenuated by OPC-14117 administration (P<0.05). In conclusion, OPC-14117 may have a potential for decreasing secondary cellular damage due to traumatic brain injury since it is as efficacious as any other compound tested in this model.
Aoyama
Naoki
N
Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan. aonao17@dream.com
Katayama
Yoichi
Y
Kawamata
Tatsuro
T
Maeda
Takeshi
T
Mori
Tatsuro
T
Yamamoto
Takamitsu
T
Kikuchi
Tetsuro
T
Uwahodo
Yasuhumi
Y
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D001929:Brain Edema / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000293:injuries* / Q000473:pathology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007189:Indans / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009336:Necrosis; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D009994:Osmolar Concentration; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013046:Specific Gravity / Q000187:drug effects; D013997:Time Factors
D000975:Antioxidants; D007189:Indans; D010879:Piperazines; C074852:OPC 14117