[Neuroprotective effect of alpha-dihydroergocryptine depends on activation of nuclear factor kappa B].
OBJECTIVE
To investigate the relationship between the neuroprotective effect of alpha-dihydroergocryptine (alpha-DHEC) and the activation of nuclear factor Kappa B (NF-Kappa B).


METHODS
Adult male rats were subjected to cerebral ischemia induced by middle cerebral artery occlusion (MCAO). DNA binding activity of NF-Kappa B was determined with electrophoretic mobility shift assay (EMSA) in animals subjected to varying durations of cerebral ischemia. Neuroapoptosis induced by ischemic damage was measured by deoxynucleotidy transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry (FCM) analysis.


RESULTS
No change was observed in nuclear NF-Kappa B DNA binding in normal animal. A low level of constitutive NF-Kappa B DNA binding was detected in animals subjected to cerebral ischemia of 1 h, and significant increase in the amount of active NF-Kappa B in nuclear extracts was observed after cerebral ischemia of 3 h, 6 h, and 12 h. Peak of NF-Kappa B DNA binding was observed at the time point of 3 h. Animals subjected to cerebral ischemia of 3 h potentially initiates neuroapoptosis and activates NF-Kappa B in nuclear extract. Alpha-DHEC (100 micrograms.kg-1 and 150 micrograms.kg-1) showed significant protective effect on neuroapoptosis-induced by cerebral ischemia of 3 h, and inhibiting NF-Kappa B activation using 100 mg.kg-1 pyrrolidinedithiocarbamate (PDTC) in the continuous presence of alpha-DHEC, the neuroprotective effect of alpha-DHEC was blocked.


CONCLUSIONS
The findings suggest that the neuroprotetive effect of alpha-DHEC may depend on the activation of NF-Kappa B.
Zheng
S Q
SQ
Department of Pharmacology, Sun Yat-Sen University of Medical Science, Guangzhou 510080, China.
Li
T
T
Xuan
Y X
YX
Lin
S Z
SZ
Chen
L J
LJ
Yan
G M
GM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002545:Brain Ischemia / Q000209:etiology / Q000517:prevention & control; D025443:Dihydroergocryptine / Q000494:pharmacology* / Q000627:therapeutic use; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000166:cytology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D016328:NF-kappa B; D018696:Neuroprotective Agents; D025443:Dihydroergocryptine