Neuroprotective effect of postischemic administration of sodium orthovanadate in rats with transient middle cerebral artery occlusion.
Orthovanadate is a competitive inhibitor of protein tyrosine phosphatases. Some of its reported biologic effects are its insulin mimetic property and its activation of phosphoinositide 3-kinase and extracellular-signal regulated kinase (ERK). The authors previously reported its neuroprotective effect on delayed neuronal death of gerbil hippocampal CA1 neurons via Akt and ERK activation after transient forebrain ischemia. In the present study, the neuroprotective effect of postischemic intraperitoneal administration of sodium orthovanadate (2 l/kg of 50-mmol/l sodium orthovanadate in saline) was investigated in rats with transient middle cerebral artery occlusion. Ischemic neuronal injury was evaluated 1 day and 28 days after ischemia. The neuroprotective effect of orthovanadate was significant in the cortex but not the caudate putamen (ischemic core) at both 1 and 28 days after ischemia. In orthovanadate group, the activities of Akt and ERK were maintained after reperfusion; they were decreased in saline group. Blood glucose level decreased but within normal range. Regional cerebral blood flow was lower than that of saline group only at 0 hours after reperfusion. These data suggest that orthovanadate has neuroprotective effects in rats with transient middle cerebral artery occlusion and that these effects are mediated by Akt and ERK activation. Furthermore, low blood glucose levels and gradual recovery of regional cerebral blood flow may contribute to neuroprotection.
Hasegawa
Yu
Y
Department of Neurosurgery, Kumamoto University School of Medicine, Kumamoto, Japan.
Hamada
Jun-Ichiro
J
Morioka
Motohiro
M
Yano
Shigetoshi
S
Kawano
Takayuki
T
Kai
Yutaka
Y
Fukunaga
Kohji
K
Ushio
Yukitaka
Y
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017072:Neostriatum / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D014638:Vanadates / Q000494:pharmacology*
D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D014638:Vanadates; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases