Post-ischemic treatment with toki-shakuyaku-san (tang-gui-shao-yao-san) prevents the impairment of spatial memory induced by repeated cerebral ischemia in rats.
Previously we have reported that Toki-shakuyaku-san (TSS) ameliorated the impairment of spatial memory induced by single cerebral ischemia (1 x 10 minutes) and scopolamine, a muscarinic receptor antagonist. In this experiment, we studied the effect of TSS on repeated cerebral ischemia (2 x 10 minutes, 1-hour interval) induced impairment of spatial memory and neuronal injury in rats. The 8-day post-ischemic treatment with TSS (30-300 mg/kg) was administered p.o. once per day. TSS dose-dependently prevented the impairment of spatial memory, neuronal death and TUNEL positive cells induced by repeated cerebral ischemia. In order to determine the mechanism of TSS, we also studied the effect of TSS on GluR2 mRNA, one of the glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) receptor subunits. Repeated cerebral ischemia significantly decreased GluR2 flop mRNA at 1 and 3 days after the occlusion. TSS (300 mg/kg) significantly suppressed the decrease in GluR2 flop at 3 days after repeated cerebral ischemia. These results suggested that the TSS has neuroprotective action which may be indirectly mediated by the AMPA receptor, and TSS may be beneficial for the treatment of cerebrovascular dementia.
Pu
Fengling
F
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Fukuoka 814-0180, Japan.
Mishima
Kenichi
K
Egashira
Nobuaki
N
Akiyoshi
Yuki
Y
Liu
An-Xin
AX
Sano
Kazunori
K
Irie
Keiichi
K
Ishibashi
Daisuke
D
Hatip-Al-Khatib
Izzettin
I
Iwasaki
Kiyo
K
Kurauchi
Kouji
K
Iwasaki
Katsunori
K
Fujiwara
Michihiro
M
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism
D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D018091:Receptors, AMPA; C413220:toki-shakuyaku-san; C104722:glutamate receptor ionotropic, AMPA 2