The Effects Of Nogo Receptor Inhibitor On Nerve Regeneration In Rat Brain After Diffusive Axonal Injury

Obiectives:To detecting the diffuse axonal injury in rat and Nogo receptor inhibitor NEP1-40 interfere with NgR and GAP-43 Protein expr-ession in rat brain. Approach the function of Nogo receptor inhibitors promoting nerve regeneration after diffuse axonal injury in rat.Methods:Sprauge-Dawley rats which weight from 250 to 300 grams are divided randomly into five groups:the normal control group, the sham-operation group(injected 25μl NS into cerebral ventricle),the DAI model group,the first treatment group(injected Nogo receptor inhib-itor NEP1-40 25μl into cerebral ventricle) and the second treatment group(injected Nogo receptor inhibitor NEP1-40 50μl into cerebral ventricle). Each group is divided into four time points, which are 1 day, 3 days,7 days and 14 days.The number of rats is five at each time point. The rats of the normal control group have no treatment. The rats of DAI model and treatment group suffer diffuse axonal injury after free-fall, the sham-operation group suffer the same impact and preparation before the surgery, but not be injured. After intracerebroventricular injection,these brain injured rats then are executed at the time points above-men-tioned.The pathological changes are observed by HE drum dyeing, and Immunohistochemistry is used to detect the the expression of NgR and GAP-43 protein.Results:1.Change of pathological section:HE staining show:Both normal control group and sham-operation group rat brain structure is clear, even and compact. The cerebral cortex, brain stem and other parts of DAI model group can be seen in focal spotting bleeding, cortical swelling, degeneration of neurons to shrink. Treatment group compare with the DAI model, swelling of brain tissue injury is mild, neuronal degeneration is also less. The second treatment group improve greater than the first.2. The expression of NgR protein decrease after DAI, with the lowest level in the third day, and gradual recovery to the normal level by the seventh day. But then gradually increase, the expression level increase significant after fourteen days and it is higher than that in the control groups and sham-operation groups. The expression of NgR protein in the the treatment groups is lower than the model groups (P<0.05). The expr-ession of NgR protein in the the second treatment groups is lower than the first (P<0.05). It is no significant difference that the sham-operation groups compare with the control (P> 0.05).3. The GAP-43 protein expression increase gradually after the head injury, the most obvious in the seventh day, then in the fourteenth day is still higher than normal expression levels, The GAP-43 protein expres-sion of the DAI groups is higher than the normal control groups and sham-operation groups (P＜.01). The expression of GAP-43 protein in the the treatment groups is higher than the model groups (P<0.05). It is no significant increase that the expression of GAP-43 protein in the second treatment group compare with the first (P>0.05). It is no signi-ficant difference that the sham-operation groups compare with the control (P> 0.05).Conclusions:1.It shows that the role of the NgR protein's inhibit nerve regeneration is gradually increased and the GAP-43 protein's role is gradually weaken after DAI injury in rats'brain.2. NEP1-40 may be reduce the expression of NgR protein and increase the expression of GAP-43, to reduce brain damage and promote regeneration after axonal injury. This effect may be facilitated to some extent when increase the amount of the NEP1-40.