Fasudil (HA1077), an intracellular calcium antagonist, improves neurological deficits and tissue potassium loss in focal cerebral ischemia in gerbils.
The effects of an intracellular calcium antagonist fasudil (HA 1077) on protein synthesis, ion derangement, brain edema, and the neurological signs associated with focal cerebral ischemia, were investigated via a nine-hour occlusion of the left common carotid artery (CCA) in Mongolian gerbils. Protein synthesis was evaluated by the amount of incorporation of [14C]methionine into the tissue. Intravenous infusion of fasudil hydrochloride (1 mg kg-1) just after CCA ligation was effective in reducing neurological deficits six and nine hours after CCA ligation, as well as loss of tissue potassium. However, fasudil did not ameliorate the brain edema or the accumulation of sodium in the tissue. On the other hand, fasudil improved the uptake of [14C]methionine, but not its incorporation into the tissue. The improved uptake of tracer into the tissue may indicate the facilitation of collateral blood flow by fasudil. These results suggest that fasudil may mitigate ischemic damage in the penumbral zone, possibly by ameliorating collateral blood flow and preventing calcium-related cell damage.
Kondoh
Y
Y
Department of Neurology, Research Institute for Brain and Blood Vessels, Akita, Japan.
Mizusawa
S
S
Murakami
M
M
Nakamichi
H
H
Nagata
K
K
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D001929:Brain Edema / Q000209:etiology; D002545:Brain Ischemia / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005849:Gerbillinae; D008297:Male; D008715:Methionine / Q000378:metabolism; D009422:Nervous System Diseases / Q000209:etiology* / Q000503:physiopathology*; D009460:Neurologic Examination; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism
D002121:Calcium Channel Blockers; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D012964:Sodium; D008715:Methionine; C049347:fasudil; D011188:Potassium