Jpn. J. Pharmacol. 78 (1), 31-37 (1998)

Time-Dependent Changes in the Ischemic Forebrain Following the Microsphere-Induced Permanent Occlusion of Cerebral Arterioles in Rats

Kayoko Okuyama, Satoko Kiuchi, Masahito Okamoto, Hitoshi Iwasaki, Hiroshi Narita and Yukitsuka Kudo

Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., 2-2-50, Kawagishi, Toda, Saitama 335-8505, Japan

Abstract: To evaluate the progression of brain edema without modification by the effect of anesthetics, we examined the local and permanent ischemia model in unanesthetized rats. The forebrain embolism was induced by intra-arterial infusion of microspheres of 50-microm diameter in freely moving rats. From 2 to 48 hr following the injection, the water-, Na- and Ca-contents progressively increased while the K content decreased in the microsphere-injected hemisphere. After the 3rd day, the water- and Na-contents gradually decreased and returned to the normal level on the 14th day. In contrast, the Ca level remained elevated even on the 56th day. The animals showed signs of neurological deficits 24 hr after the injection. In histopathological examination, large infarct areas were present in the microsphere-injected hemisphere after 24 to 48 hr. One to two weeks later, the lateral ventricle was expanded. Eight weeks after the injection, the ventricle remained expanded and newly developed infarct areas were observed in a scattered pattern around the fibrotic area. The results show the close correlation between the development of edema and the increase/decrease of Na/K contents from the onset to the recovery from edema, and their changes are similar to those in human stroke. This model enables us to evaluate not only the acute ischemic insult but also the chronic changes of the forebrain following the stroke.

Keywords: Brain edema, Ischemia, Microsphere, Ca content, Unanesthetized rat

Copyrightę The Japanese Pharmacological Society 1998

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