The Dynamic Expression Of LINGO-1and Effects Of RA On LINGO-1, GAP-43and The Number Of Synapses After Cerebral Ischemia

Object: To observe the dynamic expression of LINGO-1and the effects of RA onLINGO-1, GAP-43and the number of synapses after cerebral ischemia；to study the roleof LINGO-1in ischemic brain injury.Methods: With modified suture method, models of permanent focal cerebral ischemiawere established by middle cerebral artery occlusion of SD rats （pMCAO）. Western blotwas used to detect the expression of LINGO-1; the expression of GAP-43was detected byimmunohistochemistry techniques; the number of synapses was analyzed bytransmissionelectron microscopy. The experiment was divided into three groups: shamoperation group （sham group）, cerebral ischemia group （cerebral ischemia, CI group） andretinoic acid treatment group （RA group）.Results:①the dynamic expression of LINGO-1after cerebral ischemia: the expressionof LINGO-1at6h,1d,3d,7d,14d,21d after cerebral ischemia were significantly higherthan sham operation group, and the difference was statistically significant （p <0.01）.LINGO-1protein level started to increase at6hours, and continued to rise at1stday,however, the difference between6h and1stday was not statistically significant （p>0.05）.There is a considerable decrease at3rdday, followed by which LINGO-1protein graduallyincreased to peak at14thday.②the effect of RA on LINGO-1expression after cerebralischemia: the expression level of LINGO-1at14thday after MCAO was0.124±0.020，0.437±0.034，0.285±0.060respectively in sham, CI, and RA group.③the effect of RAon GAP-43expression: there is no GAP-43expression in sham group; the expression levelof GAP-43at1stday,3rdday and7thday after MCAO were20.48±1.79、34.38±1.89、59.08±1.76number/HP respectively; The expression of GAP-43at1^stday,3^rdday and7th day in RA group were24.93±2.37、47.35±2.59、76.20±3.12number/HP respectively④the effect of RA on the number of synapses: the number of synapses at7thday afterMCAO were sham group> RA group> CI group, and the values were8.42±0.13,5.39±0.26,1.74±0.37number/μ㎡respectively.Conclusion：LINGO-1expression is up-regulated at the early stage of the cerebralischemia and shows a certain regularity change; RA can inhibit the expression ofLINGO-1, promote the expression of GAP-43and increase the number of synapses; Itsuggests that LINGO-1is associated with cerebral ischemia. This study providesexperimental evidence for selecting the therapeutic time window on cerebral ischemia byusing LINGO-1antagonists.