Effects of antioxidant, OPC-14117, on secondary cellular damage and behavioral deficits following cortical contusion in the rat.

Abstract

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.

• Authors: Naoki Aoyama, Yoichi Katayama, Tatsuro Kawamata, Takeshi Maeda, Tatsuro Mori, Takamitsu Yamamoto, Tetsuro Kikuchi, Yasuhumi Uwahodo
• Journal: Brain research (Brain Res) Vol. 934 Issue 2 Pg. 117-24 (May 03 2002) ISSN: 0006-8993 [Print] Netherlands
• PMID: 11955474 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Indans
• Piperazines
• OPC 14117

Topics

• Animals
• Antioxidants (pharmacology, therapeutic use)
• Behavior, Animal (drug effects, physiology)
• Body Temperature (drug effects, physiology)
• Brain Edema (drug therapy, physiopathology, prevention & control)
• Brain Injuries (drug therapy, metabolism, physiopathology)
• Cell Death (drug effects, physiology)
• Cerebral Cortex (drug effects, injuries, pathology)
• Cognition Disorders (drug therapy, etiology, physiopathology)
• Hippocampus (drug effects, pathology, physiopathology)
• Indans (pharmacology, therapeutic use)
• Male
• Maze Learning (drug effects, physiology)
• Necrosis
• Nerve Degeneration (drug therapy, physiopathology, prevention & control)
• Osmolar Concentration
• Oxidative Stress (drug effects, physiology)
• Piperazines (pharmacology, therapeutic use)
• Rats
• Rats, Wistar
• Specific Gravity (drug effects)
• Time Factors