Naftidrofuryl oxalate improves impaired brain glucose metabolism after microsphere-induced cerebral embolism in rats.
The present study was designed to elucidate possible therapeutic effects of naftidrofuryl on the brain glucose metabolism after cerebral ischemia. Cerebral ischemia was induced by injecting 680 microspheres with a diameter of 48 microns into the right internal carotid artery of the rat. After ensuring the onset of symptoms of stroke on the first day after the operation, the rats were treated with intraperitoneal injections of 15 mg/kg naftidrofuryl oxalate twice a day. The behavioral and metabolic changes of operated rats were monitored up to the 5th day after surgery. The symptoms gradually faded away, from the 3rd day on, after microsphere-induced cerebral embolism. Tissue glucose and glycogen greatly increased after cerebral embolism, suggesting embolism-induced inhibition of glycolysis. To elucidate which steps in the glycolytic catabolism are inhibited after cerebral ischemia, biochemical activities of the glycolytic enzymes in the Embden-Meyerhof pathway and tricarboxylic acid cycle were determined on the 3rd day after surgery. Enzyme activities of hexokinase, phosphofructokinase and pyruvate kinase were not inhibited, but rather increased slightly after cerebral embolism. Malate dehydrogenase activity in the brain mitochondria was markedly increased after microsphere-embolism, whereas other enzyme activities in the tricarboxylic acid cycle were never inhibited by the cerebral embolism. Treatment of naftidrofuryl resulted in an appreciable reverse of the brain glucose and glycogen levels and a substantial recovery of altered enzyme activities to normal levels in the Embden-Meyerhof pathway and tricarboxylic acid cycle.(ABSTRACT TRUNCATED AT 250 WORDS)
Takeo
S
S
Department of Pharmacology, Tokyo College of Pharmacy, Japan.
Tanonaka
R
R
Miyake
K
K
Tanonaka
K
K
Taguchi
T
T
Kawakami
K
K
Ono
M
M
Hiramatsu
M
M
Okano
K
K
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D002952:Citric Acid Cycle; D005947:Glucose / Q000032:analysis / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D002542:Intracranial Embolism and Thrombosis / Q000378:metabolism*; D008297:Male; D008863:Microspheres; D009257:Nafronyl / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D009257:Nafronyl; D006003:Glycogen; D005947:Glucose