[P38 MAPK antisense oligodeoxynucleotide inhibited the brain ischemic tolerance induced by limb ischemic preconditioning].
OBJECTIVE
To better assess the role of p38 MAPK, this project was designed to investigate whether intraventricular injection of antisense oligodeoxynucleotide (As-ODN) directed against the p38 MAPK of pyramidal neurons in hippocampus could affect the brain ischemic tolerance induced by limb ischemic preconditioning (LIP).


METHODS
The rat 4-vessel occlusion global cerebral ischemic model was used. Forty-eight male Wistar rats with permanently occlusion of the bilateral vertebral arteries were divided into 8 groups (n=6): sham, LIP, brain ischemic insult, LIP + brain ischemic insult, distilled water + LIP + brain ischemic insult, p38 MAPK As-ODN and p38 MAPK As-ODN + LIP + brain ischemic insult (two doses of 5 nmol/5 microl and 10 nmol/5 microl were used) groups. Thionin staining was used for observing histological changes of the hippocampus.


RESULTS
No significant delayed neuronal death (DND) was detected in the CA1 hippocampus of the rats that underwent sham and LIP operation. Brain ischemic insult for 8 min induced obvious DND as represented with the increase in histological grade (HG) and decrease in neuronal density (ND) significantly compared with sham and LIP groups. LIP protected the CA1 hippocampal pyramidal neurons against DND induced by global brain ischemic insult, suggesting the occurrence of brain ischemic tolerance. However, pretreatment with p38 MAPK As-ODN effectively blocked the ischemic tolerance induced by LIP in a dose dependent manner.


CONCLUSIONS
It could be concluded that p38 MAPK plays an important role in the brain ischemic tolerance induced by LIP.
Sun
Xiao-cai
XC
Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, China.
Li
Wen-bin
WB
Li
Qing-jun
QJ
Zhang
Min
M
Xian
Xiao-hui
XH
Li
Shu-qin
SQ
Qi
Jie
J
Liu
Hui-ru
HR
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology; D016923:Cell Death; D005121:Extremities / Q000098:blood supply*; D006624:Hippocampus / Q000473:pathology; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*
D020319:Oligodeoxyribonucleotides, Antisense; D048051:p38 Mitogen-Activated Protein Kinases