Borgens R B, Bohnert D
Institute for Applied Neurology, Center for Paralysis Research, Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907-1244, USA.
J Neurosci Res. 2001 Dec 15;66(6):1179-86. doi: 10.1002/jnr.1254.
Arguably a seminal event in most trauma and disease is the breakdown of the cell membrane. In most cells, this is first observed as a collapse of the axolemmas barrier properties allowing a derangement of ions to occur, leading to a progressive dissolution of the cell or its process. We have shown that an artificial sealing of mechanically damaged membranes by topical application of hydrophilic polymers such as polyethylene glycol (PEG) immediately restores variable levels of nerve impulse conduction through the lesion. This was documented by a rapid recovery of somatosensory evoked potential (SSEP) conduction, and by recovery of the cutaneous trunchi muscle (CTM) reflex in PEG-treated animals. The CTM reflex is a sensorimotor behavior dependent on an intact (and identified) white matter tract within the ventrolateral funiculus of the spinal cord, and is thus an excellent index of white matter integrity. We show that PEG can be safely introduced into the bloodstream by several routes of administration. Using a fluorescein decorated PEG, we demonstrate that the polymer specifically targets the hemorrhagic contusion of the adult guinea pig spinal cord when administered through the vasculature, but not intact regions of the spinal cord. A single subcutaneous injection (30% weight by weight in sterile saline) made 6 hr after a standardized spinal cord contusion in adult guinea pigs was sufficient to produce a rapid recovery of SSEP propagation through the lesion in only PEG-treated animals, accompanied by a statistically significant recovery of the CTM reflex. These data suggest that parenterally administered PEG may be a novel treatment for not only spinal injury, but head injury and stroke as well.
在大多数创伤和疾病中,细胞膜的破裂可以说是一个具有开创性的事件。在大多数细胞中,这首先表现为轴膜屏障特性的崩溃,导致离子紊乱,进而导致细胞或其突起的逐渐溶解。我们已经表明,通过局部应用亲水性聚合物(如聚乙二醇,PEG)对机械损伤的膜进行人工密封,可以立即恢复通过损伤部位的不同程度的神经冲动传导。这通过体感诱发电位(SSEP)传导的快速恢复以及PEG处理动物的皮节肌(CTM)反射的恢复得到了证实。CTM反射是一种感觉运动行为,依赖于脊髓腹外侧索内完整的(且已确定的)白质束,因此是白质完整性的一个极好指标。我们表明,PEG可以通过几种给药途径安全地引入血液中。使用荧光素修饰的PEG,我们证明当通过血管系统给药时,该聚合物特异性地靶向成年豚鼠脊髓的出血性挫伤部位,而不是脊髓的完整区域。在成年豚鼠进行标准化脊髓挫伤6小时后,单次皮下注射(在无菌盐水中按重量计30%)仅在PEG处理的动物中足以使SSEP通过损伤部位的传播迅速恢复,同时CTM反射有统计学意义的恢复。这些数据表明,胃肠外给药的PEG可能不仅是脊髓损伤的一种新治疗方法,也是头部损伤和中风的新治疗方法。