cAMP诱导大鼠脊髓损伤后神经再生

目的观察在体给入环磷酸腺苷(cyclic adinosine monophosphate,cAMP)对大鼠脊髓损伤后神经再生的作用。方法56只SD大鼠制成脊髓T10背侧半切断损伤模型,随机分为六组。各组分别在脊髓损伤局部、大脑运动皮层和T6蛛网膜下腔内给入cAMP或生理盐水。动物存活6周后处死,制作脊髓组织切片,通过免疫组化染色观察损伤区局部神经丝的分布;通过皮质脊髓束和脊髓顺行追踪观察皮质脊髓束和脊髓神经纤维的再生;通过动物后肢运动BBB评分观察后肢运动功能恢复的程度,并以此来评价治疗措施的脊髓损伤修复效果。结果用三种方式给入cAMP,损伤区神经丝沿脊髓纵轴延伸分布,但未与尾端重新连接。在蛛网膜下腔给入cAMP无明显的脊髓神经再生;在损伤区局部和大脑运动皮层给入cAMP,损伤区可见大量脊髓再生纤维,包括部分皮质脊髓神经纤维再生。各组动物在术后4～5周均恢复正常行走,BBB评分超过20分。结论在脊髓损伤局部和在大脑运动皮层给入cAMP能诱导大鼠脊髓损伤后神经再生,但尚不能达到有效促进实验动物后肢运动功能的效果。

cAMP induces axonal regeneration in spinal cord injury of rats

Objective cAMP promotes neurite outgrowth in vitro. The study is aimed to understand whether cAMP can repair spinal cord injury of rats. Methods 56 rats models of spinal cord hemisection were adopted and randomly distributed into six groups. Dibutyryl-cAMP or physiological saline was injected either once in the motor cortex with an amount of 6 ml of 50 mmol/L cAMP, or continuously infused through a polyethylene tube connecting with a micro-pump in the spinal lesion area or in the subarachnoid space with a total amount of 72 ml of 10 mmol/L cAMP for 72 h. The distribution of neurofilament (NF) in the lesion area was observed by immunohistochemistry. Corticospinal tracts (CST) and spinal axons regeneration were investigated by CST and spinal axons anterograde tracing with biotinylated dextran amine (BDA). The function of hindlimb movements were evaluated by BBB scales and as a reference to assess the repairing effect of treating strategy. Results NF were densely distributed and extended in the lesion area in the cAMP groups, but no connection could be found with the NF in the caudal. No axonal regeneration could be achieved when cAMP was input into the subarachnoid space. Many regenerated axons, including some CST axonal regeneration were presented in the lesion areas in cAMP groups though no continuous long regenerated axons traversed the lesion area, while there was no regenerated axon in the lesion areas in the control groups. All the rats restored to normally walk 4 to 5 weeks after operations, BBB scale exceed 20, and no significant difference between cAMP groups and control groups by comparing the BBB scales of hindlimb movements. Conclusion cAMP injected in the brain cortex or continuously infused in the spinal lesion area can induce the axonal regeneration and is beneficial to repair the spinal cord injury, but could not directly promote hindlimb movements recovering.