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