Ditor David S, John Sunil M, Roy Josee, Marx Jeffrey C, Kittmer Colin, Weaver Lynne C
Spinal Cord Injury Team, BioTherapeutics Research Group, Robarts Research Institute, London, Ontario, Canada.
J Neurosci Res. 2007 May 15;85(7):1458-67. doi: 10.1002/jnr.21283.
The purpose of this study was to determine the long-term effects of polyethylene glycol (PEG) and magnesium sulfate (MgSO(4)) on clinically relevant motor, sensory, and autonomic outcomes after spinal cord injury (SCI). Rats were injured by clip compression (50 g; T4) and treated 15 min and 6 hr postinjury intravenously (tail vein) with PEG (1 g/kg, 30% w/w in saline; n = 11), MgSO(4) (300 mg/kg; n = 5), PEG + MgSO(4) (n = 6), or saline (n = 10). Behavioral testing lasted for 6 weeks, followed by histological analysis of the spinal cord. Both PEG and MgSO(4) resulted in enhanced locomotor recovery and lower susceptibility to neuropathic pain (mechanical allodynia) compared with saline. At 6 weeks, BBB scores were 7.3 +/- 0.2, 7.7 +/- 0.4, and 6.4 +/- 0.6 in PEG-treated, MgSO(4)-treated, and saline-treated control groups, respectively. Likewise, at 6 weeks PEG-, MgSO(4)-, and saline-treated control animals showed 3.5 +/- 0.4, 2.8 +/- 0.9, and 5.0 +/- 0.5 avoidance responses to at-level touch, respectively. PEG + MgSO(4) improved locomotor recovery and reduced pain but did not provide additional benefit compared with either treatment alone. Neither treatment, nor their combination, attenuated mean arterial pressure (MAP) increases during autonomic dysreflexia. However, saline-treated controls had significantly lower resting MAP than PEG-treated rats and tended to have lower resting MAP than MgSO(4)-treated rats 6 weeks postinjury. MgSO(4) treatment and PEG + MgSO(4) treatment resulted in significant increases in dorsal myelin sparing, and the latter resulted in significant reductions in lesion volume, compared with saline-treated controls. Furthermore, mean lesion volumes correlated negatively with the corresponding mean BBB scores and positively with the corresponding mean pain scores. In conclusion, both PEG and MgSO(4) enhanced long-term clinical outcomes after SCI.
本研究的目的是确定聚乙二醇(PEG)和硫酸镁(MgSO₄)对脊髓损伤(SCI)后临床相关运动、感觉和自主神经功能结局的长期影响。大鼠通过夹压法(50 g;T4)造成损伤,并在损伤后15分钟和6小时经静脉(尾静脉)给予PEG(1 g/kg,30% w/w生理盐水;n = 11)、MgSO₄(300 mg/kg;n = 5)、PEG + MgSO₄(n = 6)或生理盐水(n = 10)。行为测试持续6周,随后对脊髓进行组织学分析。与生理盐水相比,PEG和MgSO₄均能促进运动功能恢复,并降低对神经性疼痛(机械性异常性疼痛)的易感性。在6周时,PEG治疗组、MgSO₄治疗组和生理盐水治疗对照组的BBB评分分别为7.3±0.2、7.7±0.4和6.4±0.6。同样,在6周时,PEG、MgSO₄和生理盐水治疗的对照动物对损伤平面触摸的回避反应分别为3.5±0.4、2.8±0.9和5.0±0.5。PEG + MgSO₄改善了运动功能恢复并减轻了疼痛,但与单独使用任何一种治疗相比,并未提供额外的益处。两种治疗方法及其联合使用均未减轻自主神经反射异常期间平均动脉压(MAP)的升高。然而,生理盐水治疗的对照组在损伤后6周时的静息MAP显著低于PEG治疗的大鼠,且倾向于低于MgSO₄治疗的大鼠。与生理盐水治疗的对照组相比,MgSO₄治疗组和PEG + MgSO₄治疗组的背侧髓鞘保留显著增加,后者的损伤体积显著减小。此外,平均损伤体积与相应的平均BBB评分呈负相关,与相应的平均疼痛评分呈正相关。总之,PEG和MgSO₄均可改善SCI后的长期临床结局。