Neuroprotective effect of a peptide inhibitor of c-Jun N-terminal kinase on global cerebral ischemia in gerbils
10.3760/cma.j.issn.1671-8925.2007.04.006
- VernacularTitle:一种C-Jun N-末端激酶肽抑制剂在沙土鼠全脑缺血中的保护作用
- Author:
Li-Ke SAI
1
;
Hao WEN
;
Nozaki KAZUHIKO
;
Takagi YASUSHI
;
Hayashi JUNYA
;
Yi-Zhao CHEN
;
Hashimoto NOBUO
Author Information
1. 新疆医科大学附属第一医院(心血管病专科医院)
- Keywords:
Delayed neuronal death;
Global cerebral ischemia;
C-Jun N-terminal kinase;
JNK inhibitor;
Hppocampal gyrus;
Gerbils
- From:
Chinese Journal of Neuromedicine
2007;6(4):343-348
- CountryChina
- Language:Chinese
-
Abstract:
Objective To assess the effect of D-JNKI1, an inhibitor of c-Jun N-terminal kinase (JNK), on delayed neuronal death (DND) in a gerbil model of transient global cerebral ischemia, so as to further study the roles of JNK activation in mediating neuronal cell death in brain ischemia. Methods Fifty-five Mongolian gerbils were randomly divided into 11 groups. Animals (n=35) assigned into 7 groups (n=5 per group) were subjected to 5-min occlusion of bilateral common carotid arteries (BCCAO);among the 7 groups, different doses of D-JNKI1 (0.00012, 0.0012, 0.012, 0.12, 1.2 μmol/L in 2 μL PBS,n=5 each) were administered stereotaxically into right lateral ventricles 3 h after reperfusion; the control group (n=5) received 2 μL PBS; and another group (n=5) received 1.2 μmol/L of D-JNKI1 in 0.5 mL PBS intraperitoneally. Sham-operated animals (n=5) only received the exposure of bilateral common carotid arteries without occlusion. Three groups (n=5 in each) were pretreated with D-JNKI1 (0.00012,0.0012 μmol/L in 2 μL PBS) or only 2 μL PBS 30 min before 2-min BCCAO, and subjected to 5-min BCCAO 48 h after the first ischemic insult. All animals were sacrificed 4 d after 5-min BCCAO and prepared for frozen section and Nissl staining. Results The treatment with D-JNKI 3 h after 5-min ischemia was neuroprotective with a maximum effect at a dose of 0.0012 μmol/L. Pretreatment with D-JNKI augmented ischemic tolerance induced by 2-min ischemia. Conclusion D-JNKI1 has a potential neuroprotective effect on DND in CA1 of hippocampus in gerbils with global cerebral ischemia-reperfusion injury.
