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皮下注射三嵌段共聚物可使脊髓损伤恢复。

Subcutaneous tri-block copolymer produces recovery from spinal cord injury.

作者信息

Borgens Richard B, Bohnert Debbie, Duerstock Brad, Spomar Daniel, Lee Raphael C

机构信息

Center for Paralysis Research, School of Veterinary Medicine, Purdue University, West Lafayette, Indiana 47907, USA.

出版信息

J Neurosci Res. 2004 Apr 1;76(1):141-54. doi: 10.1002/jnr.20053.

Abstract

We have studied the ability of nonionic detergents and hydrophilic polymers to seal permeabilized membranes of damaged cells, rescuing them from progressive dissolution, degeneration, and death. We report that a single subcutaneous injection of the tri-block copolymer, Poloxamer 188 (P188) 6 hr after a severe compression of the adult guinea pig spinal cord is able to: (1). preserve the anatomic integrity of the cord; (2). produce a rapid recovery of nerve impulse conduction through the lesion; and (3). produce a behavioral recovery of a spinal cord dependent long tract spinal cord reflex. These observations stood out against a control group in blinded evaluation. Conduction through the lesion was monitored by stimulating the tibial nerve of the hind limb, and measuring the arrival of evoked potentials at the contralateral sensory cortex of the brain (somatosensory evoked potentials; SSEP). Behavioral recovery was determined by a return of sensitivity of formerly areflexic receptive fields of the cutaneous trunchi muscle (CTM) reflex. This contraction of back skin in response to tactile stimulation is totally dependent on the integrity of an identified bilateral column of ascending long tract axons. A statistically significant recovery of both SSEP conduction through the lesion and the CTM reflex occurred in P188-treated animals compared to vehicle-treated controls. Quantitative 3D computer reconstruction of the lesioned vertebral segment of spinal cord revealed a statistically significant sparing of spinal cord parenchyma and a significant reduction in cavitation of the spinal cord compared to control animals We determined that the proportion of P188-treated animals that recovered evoked potentials were nearly identical to that produced by a subcutaneous injection of polyethylene glycol (PEG). In contrast, P188 was not as effective as PEG in producing a recovery of CTM functioning. We discuss the likely differences in the mechanisms of action of these two polymers, and the possibilities inherent in a combined treatment.

摘要

我们研究了非离子型去污剂和亲水性聚合物封闭受损细胞透化膜的能力,使其免于渐进性溶解、退化和死亡。我们报告称,在成年豚鼠脊髓严重受压6小时后单次皮下注射三嵌段共聚物泊洛沙姆188(P188)能够:(1)保持脊髓的解剖完整性;(2)使神经冲动通过损伤部位快速恢复传导;(3)使依赖脊髓的长束脊髓反射的行为恢复。在盲法评估中,这些观察结果在对照组中脱颖而出。通过刺激后肢胫神经并测量诱发电位在对侧大脑感觉皮层(体感诱发电位;SSEP)的到达情况来监测通过损伤部位的传导。行为恢复通过皮肤躯干肌(CTM)反射先前无反射的感受野的敏感性恢复来确定。这种对触觉刺激的背部皮肤收缩完全依赖于已确定的双侧上升长束轴突柱的完整性。与载体处理的对照组相比,P188处理的动物在通过损伤部位的SSEP传导和CTM反射方面均有统计学意义的恢复。对脊髓损伤椎体节段进行定量三维计算机重建显示,与对照动物相比,脊髓实质有统计学意义的保留,脊髓空洞形成显著减少。我们确定,恢复诱发电位的P188处理动物的比例与皮下注射聚乙二醇(PEG)产生的比例几乎相同。相比之下,P188在使CTM功能恢复方面不如PEG有效。我们讨论了这两种聚合物作用机制可能存在的差异以及联合治疗的内在可能性。

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