Kayoko Okuyama, Satoko Kiuchi, Masahito Okamoto, Hiroshi Narita and Yukitsuka
Kudo
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., 2 - 2 - 50,
Kawagishi, Toda, Saitama 335 - 8505, Japan
Abstract: One of the most common acute complications of stroke
is brain edema. Treatment of edema is recommended when the condition of
the patients is deteriorating. The present study was undertaken to evaluate
the effect of T-477 [(R)-(+)-2-(4-chlorophenyl)-2,3-dihydro-4-diethyl
aminoacetyl-4H-1,4-benzothiazine hydrochloride], a novel neuronal
Na+ and Ca2+ channel blocker, on brain edema in rats.
Cerebral ischemia was induced by intra-arterial infusion of 1000 microspheres
into the forebrain of freely moving rats, resulting in brain edema. T-477
was intravenously infused continuously for 24 h or twice for 3 h with a
3-h interval between infusions immediately after microsphere injection.
T-477 dose-dependently inhibited the increase in brain water content by
both infusion procedures; the inhibition was statistically significant at
doses of 25 mg/kg per 24 h and 14 mg/kg per 9 h. Additionally, infusion
of T-477 at a dose of 14 mg/kg per 9 h significantly inhibited the decrease
in K content and the increase in Ca content of the forebrain. In conclusion,
T-477 prevents brain edema following microsphere-induced cerebral embolism
in rats.
Keywords: Brain edema, Ischemia, Microsphere, Unanesthetized rat, T-477