A Study of Behavioral Pharmacology and Histopathology with Stroke Rats Induced by N^G-nitro-L-arginine (L-NNA) as an NO Synthetic Inhibitor

Abstract

Rats treated with L-NNA develop stroke to serve as an animal model of multiple infarct dementia. A study of behavioral pharmacology and histopathology was conducted to clarify this characteristics in detail. In this study, male, 4-week old Wistar rats were fed with SP food containing L-NNA at 0.023%, and thus development of stroke was induced. This was followed by a wash-out period to observe behavioral changes such as learning impairment, and remaining cerebrovascular disease in the rats which had recovered most of neurologic symptoms which usually accompany stroke. Body weight, food consumption, and blood pressure were determined, while neurologic symptoms were observed during the test period. A cerebrovascular damage was detected non-invasively by Magnetic Resonance Imaging, and examined histologically. As a result, it was found that L-NNA induced in rats significant body weight decrease and severe hypertension, aggravated offensiveness and sensitivity, also led to the occurrence of stroke. The wash-out period set after onset of stroke helped to mitigate neurologic symptom and body weight decrease; however, learning impairment remained. The area of high-level MRI signal in the cerebral cortex corresponded to a broad range of cerebral infarct covering histologic edema and vascular damage. Thus, the study results imply that L-NNA-induced stroke rats can be used as an animal model of cerebrovascular dementia, and a wide range of histologic edema can be detected non-invasively by MRI.