実験的脳梗塞に対するbifemelane hydrochlorideの効果

Abstract

Bifemelane hydrochloride is a new substance which exhibits antianoxic and memory retrieval effects in cases of ischemic cerebral damage. Recent clinical trials have also revealed favorable effects on vascular dementia.This study was designed to comfirm neuropathologically the effects of this substance on ischemic changes in the brains of Mongolian gerbils caused by ligated left carotid arteries. Two-hundred 8-week-old Mongolian gerbils were divided into 4 groups of 50 animals each. Bifemelane hydrochloride was administered intraperitoneally to the animals in 1.0% physiological saline at doses of 25mg/kg body weight. Bifemelane hydrochloride was given to group II 30 minutes before, and twice to group III 30 minutes before and after the ligation procedure. Group I served as control. This group was administered intraperitoneally the same volume of physiological saline as bifemelane hydrochloride solution used for animals with the same body weight. Group IV was prepared for an observation of vascular permeability after administering bifemelane hydrochloride by intravenous injection of Evans blue. All the animals were sacrificed 3 hours after the ligation procedure by perfusion fixation and were observed with a microscope.The survival rates and the neurological deficits did not vary significantly between groups. The incidence of prominent neurological changes in the brains of group I, II and III were 62, 54 and 54% respectively. Group I displayed a generalized reduction of stainability and widely dispersed severe ischemic lesions with a spongy state and edema, especially, in white matter and the caudate nucleus. These morphological changes expanded out from periventricular areas, and were demarcated from deeply stained normal tissues.Hippocampus samples from group I subjects showed decreased neuronal cells, vacuolar degeneration of these cells and irregular dendritic trees. Electron microscopic observations of group I specimens revealed degeneration of endothelial cells, intracellular edema, and swelling of neuronal mitochondria. Histopathological changes of group II and III subjects administered bifemelane hydrochloride were generally not serious, and boundary areas of the ischemic lesions of these subjects appeared to be intermingled with normal histological figures. Electron microscopic examination of group II and III subjects revealed that a considerable amount of organelles, such as mitochondria, microtubules, synaptic vesicles, and membranes of neuronal cells, kept their ordinal structures in the intermingling state. Evans blue transdated slightly to ischemic lesions of the animals administered bifemelane hydrochloride. Neuropathological changes observed in group I were somewhat similar to those in the brains of patients with vascular dementia; therefore, slight changes manifested in groups II and III should be regarded as evidence suggesting the utility of bifemelane hydrochloride in treating vascular dementia.