Reversal by NS-7, a neuroprotective compound, of the decrease in transcription factor CREB mRNA expression in rat brain after permanent middle cerebral artery occlusion.
The effect of a neuroprotective agent NS-7 on changes in mRNA expressions for cyclic AMP responsive element binding protein (CREB) and several neurotrophins was examined in the rat cerebral cortex after permanent middle cerebral artery occlusion (MCAO). Significant reduction in mRNA expressions for CREB was observed at 24h after MCAO. NS-7 (0.5mg/kg), when injected at 6h after MCAO, significantly reversed the decreased expression for CREB mRNA. In addition, the mRNA expression for basic fibroblast growth factor (bFGF) was also significantly enhanced by NS-7 in MCA-occluded but not in sham-operated rats. On the other hand, the mRNAs for interluekin-6 and inducible-type nitric oxide synthase were markedly induced in the cerebral cortex of MCA-occluded rats, which was not significantly reversed by NS-7. Therefore, it is suggested that the reversal of decrease in CREB mRNA and concomitant increase in mRNA expression for bFGF may contribute to the neuroprotective action of NS-7.
Hirouchi
M
M
Research Laboratories, Nippon Shinyaku Co. Ltd., Nishiohji Hachijo Minami-ku, 601-8550, Kyoto, Japan. m.hirouchi@po.nippon-shinyaku.co.jp
Itoh
Y
Y
Aoki
Y
Y
Oka
M
M
Ukai
Y
Y
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002536:Cerebral Arteries; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
C106144:4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011743:Pyrimidines; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2