Electroconvulsive seizure-induced VEGF is correlated with neuroprotective effects against cerebral infarction: Involvement of the phosphatidylinositol-3 kinase/Akt pathway.
The present study demonstrates the cytoprotective effect of electrical convulsive stimulation (ECS) as a potential neuroprotective vascular endothelial growth factor (VEGF) inducer against ischemic insult. Phosphatidylinositol-3 kinase/Akt (PI3K/Akt) is thought to be an important factor that mediates neuroprotection. However, the signaling pathways in the brain in vivo after ECS remain unclear. We measured and compared infarction volumes to investigate the effect of ECS on cerebral infarction induced by permanent middle cerebral artery occlusion in rats. We evaluated the effects of pretreatment with Wortmannin (Wort), a specific PI3K inhibitor of ECS-induced neuroprotection against infarction volumes. To clarify the relationship between PI3K/Akt activation and neuroprotection, we used immunoblot analysis to determine the amounts of p-Akt and VEGF proteins present after ECS with or without Wort treatment. Neuroprotective effects of ECS (pretreatment with a single ECS 6h before ischemia) were prevented by Wort pretreatment, which indicates that the PI3K/Akt pathway may mediate ECS-dependent protection. ECS induced p-Akt and VEGF and ECS pretreatment enhanced ischemia-induced VEGF, both of which were prevented by Wort pretreatment. These results suggest that a single ECS induces p-Akt and that ECS plays an important role in neuroprotection against the cerebral ischemia through VEGF induction.
Fujiki
Minoru
M
Department of Neurosurgery, School of Medicine, Idaigaoka, Hasama-machi, Oita 879-5593, Japan. fujiki@oita-u.ac.jp
Abe
Eiji
E
Nagai
Yasuyuki
Y
Shiqi
Kong
K
Kubo
Takeshi
T
Ishii
Keisuke
K
Abe
Tatsuya
T
Kobayashi
Hidenori
H
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002544:Cerebral Infarction / Q000378:metabolism* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D004597:Electroshock; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt