Experiment Of ChABC On Recovery Of Spinal Cord Injury In Rats

Background:We all know that spinal cord injury(SCI) can result in dramatic disability, including both negative symptoms (such as loss of voluntary movementand tactile sensibility) and positive symptoms (such as chronic pain and spasticity).Although many patients show some spontaneous recovery after injury, most patients with significant cord damage have permanent symptoms. Moreover, damage to the spinal cord, whether caused by injury or disease, cannot currently be repaired by any therapy. Yet there is now considerable optimism among neurobiologists that effective clinical therapies are within reach.This optimism is prompted on the one hand by a great increase in our understanding of the consequences of SCI and the reasons for failure of spontaneous repair, and on the other hand by an increasing number of treatments that have promoted functional improvements in experimental models of SCI. While several treatments have shown marked protection of the cord in animal models, none has translated very successfully to human patients. The causes of regenerative failure in the CNS are a combination of the inhospitable nature of the environment of the damaged adult CNS, and the intrinsically feeble regenerative abilities of CNS axons.The inhospitable CNS environment inhibits regeneration through the formation of inhibitory scar tissue,through the presence of inhibitory molecules the surface of oligodendrocytes and astrocyte, The main axon growth inhibitory molecules have been identified in glial scar tissue: chondroitin sulphate proteoglycans (CSPGs). After SCI intrathecal treatment with ChABC degraded CSPGs at the injury site, upregulated the regeneration of axon in injured neurons, and promoted the function recovery.But there are no report that whether the CSPGs can has effect on the regeneration of neuron and activation on glia cell after SCI, especially in situ. Objective:To investigate the effect and the mechanism of CSPGs on reparation in spinal cord injury of rats through using the method of Allen's WD to make the animal model of spinal cord injury of rats, administrating ChABC in subarachniod space, observing the change of motion evoked potential and hind limb motor function, detecting the level of GFAP,NF200 and the express of apoptosis associated protein of nerve cell in spinal cord.Materials and Methods:Seventy-two SD rats were randomly divided into sham group, control (saline) group and experimental (ChABC) group, and Twenty-four for each group. The SCI model of contusion was established according to the method of Allen's and then the saline and ChABC group were treated every day for 1 week with 6μl saline, and 6μl ChABC respectively by subarachnoid space catheter placed near the injury site. There were no injury and treat for the sham group. In 1d, 1w, 2w and 4w, the rats were killed, then taked the spnial cord out about 5mm long which included the injuried spinal cord. Immunocytochemistry and image analysis methods were used to detect the change of GFAP, NF200, Bcl-2, Bax protein in the injuried spinal cord.. The morphous of the remnant injured spinal cord tissue was detected by HE and Nissl staining.Result:1. The contusion model was built and the plastic tube was situated in subarachnoid space successfully2. The NF200 neurons and OD scale, and the area of GFAP increased after injury. Significantly differences for NF200 neurons and OD scale between the control and ChABC group from 2w to 4w (P<0.05), but no difference in 1d and 1w. There were no significantly difference for the area of GFAP which increased after injury in 1d,1w,4w after injury between the saline and ChABC group ,but it had significantly difference in 2w(P<0.05), and the ChABC group is smaller than the saline group. We also found that the glial scar of ChABC group was smaller than saline group by HE staining. There was no difference of the NF200 neurons, OD scale and the area of GFAP among 1d, 1w, 2w and 4w in the sham group, but smaller than the saline group or the ChABC group. and also had no glial scar in this group. The morphous was better than the other two groups.3. The levels of Bax protein in control group were significantly increased as compared with those in ChABC group, and the level reached peak at 1d after spinal cord injury. The levels Bcl-2 proteins were positive in both groups. The levels of Bax protein in ChABC group were significantly decreased but the levels of Bcl-2 protein were obviously increased as compared with those in control group.4.The scale of BBB score was increased significantly in experimental group at 2w,4w postinjury compared with control group; The latency N1 wave of MEP in experimental group was significantly shorted as compared with control group.Conclusions:1. ChABC can promote the motor function recovery after spinal cord injury.2. ChABC can inhibit abnormal expression of Bax protein, increase the expression of Bcl-2 protein then inhibits apoptosis after spinal cord injury.3. The ChABC can enhance the recovery of neuron, attenuate the glial scar and protect the injured spinal tissue after SCI.