甲基强的松龙影响脊髓损伤后内源性神经干细胞的迁移

Methylprednisolone effects on the migration of endogenous neural stem cells after spinal cord injury

背景:脊髓损伤后,内源性神经干细胞发生增殖及迁移,修复受损伤组织。甲基强的松龙作为临床用药,其对于内源性神经干细胞的作用是未知的。目的:探讨甲基强的松龙对大鼠脊髓损伤后内源性神经干细胞增殖和迁移的影响。方法:75只SD大鼠采用Allen法建立T10平面完全性截瘫模型,随机均分成3组:甲基强的松龙组、生理盐水组和模型组。甲基强的松龙组将1 g/L甲基强的松龙溶液10 min内按30 mg/kg的剂量腹腔注射,随后23 h按5.4 mg/(kg·h)的剂量注射,生理盐水组以相同的剂量注射生理盐水,模型组不注射任何溶剂。脊髓损伤后7,14,21,28 d行体感诱发电位检测神经功能恢复情况,BBB运动等级评分测定下肢运动功能。取损伤节段脊髓,进行免疫组化Brd U及Nestin染色。结果与结论:(1)各组均有大量的Brd U和Nestin着色细胞,均在14 d达到高峰;(2)甲基强的松龙组能够抑制BrdU和Nestin单一着色及双着色细胞,抑制内源性神经干细胞的增殖和迁移;(3)BBB评分显示甲基强的松龙不能够显著改善四肢运动功能;(4)甲基强的松龙对于运动诱发电位潜伏期没有显著作用,但是可以促进损伤脊髓神经传导的恢复;(5)结果表明,甲基强的松龙能抑制脊髓损伤后内源性神经干细胞的增殖和迁移,对于脊髓损伤的修复具有一定阻碍作用。

BACKGROUND： After spinal cord injury, endogenous neural stem cells are activated to proliferate and migrate to repair damaged tissue. As a clinical medicine, methylprednisolone shows a lot of functions, but its effects on endogenous neural stem cells are still unknown. OBJECTIVE： To explore the effects of methylprednisolone on the proliferation and migration of endogenous neural stem cells after spinal cord injury. METHODS： Seventy-five Sprague-Dawley rats were used to make animal models of T10 complete paraplegia using Allen＇s method, and randomized into methylprednisolone, normal saline and model groups. Rats in these three groups were given intraperitoneal injection of 1 g/L methylprednisolone solution at a dose of 30 mg/kg for 10 minutes and at a dose of 5.4 mg/kg/h for 23 hours, given intraperitoneal injection of normal saline at the same dose and given no treatment, respectively. Neurological and motor functions were assessed by somatosensory evoked potential and Basso Beattie Bresnahan scores at 7, 14, 21, 28 days after spinal cord injury. Brd U and Nestin staining of the injured spinal cord segment was conducted. RESULTS AND CONCLUSION： A large amount of Brd U- and Nestin-positive cells were visible in all the groups, and the number of these cells reached the peach at 14 days after spinal cord injury. Methylprednisolone was found to inhibit BrdU-, Nestin- or double-positive cells, indicating methylprednisolone can inhibit the proliferation and migration of endogenous neural stem cells. The results of Basso Beattie Bresnahan scores showed no notable improvement in the motor function of the limbs. Methylprednisolone also showed no significant effects on the motor evoked potential latency, but promoted nerve conduction recovery. All these findings indicate that methylprednisolone has some hindering effects on spinal cord repair by inhibiting the proliferation and migration of endogenous neural stem cells after spinal cord injury.