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 +/- 19.9 cells/min 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. (C) 2002 Elsevier Science B.V. All rights reserved.