The mechanism and protective effects of NgR1 antagonist on cortical axons after cortical infarction in rats
10.3760/cma.j.issn.1671-0282.2012.09.015
- VernacularTitle:NgR1拮抗剂对脑梗死后轴突损伤的保护作用
- Author:
Xin LI
;
Jie CAI
;
Hongyan WEI
;
Chunlin HU
;
Xiaoli JIN
;
Hong ZHAN
;
Xiaoxing LIAO
- Publication Type:Journal Article
- Keywords:
Nogo-66 receptor;
Cortical infarction;
Axon;
Regeneration;
Signal pathway
- From:
Chinese Journal of Emergency Medicine
2012;21(9):981-986
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the protective effects of soluble Nogo-66 receptor (NgR1 )antagonist (sNgR1-Fc) on cortical axons after cortical infarction in rats,and to study the phenomenon and molecular mechanism of its protective effects on and regeneration of axons.Methods The cortical infarction was induced by photochemistry,termed photothrombotic cortical injury (PCI).Fifteen Sprague Dawley rats were randomly divided into three groups:Sham-operated group,PBS (phosphate buffered solution) group,and s-NgR1-Fc group.In PBS group,PBS was injected into the lateral ventricle of rats; and in sNgR1-Fc group,sNgR1-Fc was injected instead of PBS. The ipsilateral cortex with lesion was harvested for histomorphometry and transmission electron microscope observation 7 days after PCI. Proteins including GTP-RhoA,p-JNK,p-c-JUN and p-ATF-2 were detected by Western blot,as well as Total-J and Total-RhoA.Results The cortical infarction in rats was successfully induced by photochemistry.Compared with sham-operated group,the pathological changes in PBS groups were more serious,including extensive edema or disappearance of axoplasm of fiber without medulla sheath involved and extensive thickening or layer derangement in axoplasm of fiber with medulla sheath involved.These changes were improved significantly after sNgR1-Fc treatment.The levels of GTP-RhoA,p-JNK1,p-JNK2,p-c-JUN and p-ATF-2 in the PBS group were significantly higher than those in the sham-operation group ( P ＜ 0.05 ),whereas the levels of Total-RhoA,Total-JNKl and Total-JNK2 were not different significantly between these two groups (P ＞0.05 ).The sNgR1-Fc treatment up-regulated the levels of these proteins ( P ＜ 0.05 ).Conclusions There is pathological change in axon induced by cerebral hypoxia-ischemia for a long period after cortical infarction.The mechanisms may be associated with RhoA/ROCK/JNK/c-Jun signal way,which is activated by ischemia injury and related to the inhibition of regeneration in axon.Our study shows that NgR1-Fc may inhibit this pathway significantly,and then promote the regeneration of axon partially.
