Rapid recovery from spinal cord injury after subcutaneously administered polyethylene glycol.
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.
Borgens
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RB
Institute for Applied Neurology, Center for Paralysis Research, Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907-1244, USA. cpr@vet.purdue.edu
Bohnert
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D000818:Animals; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects / Q000502:physiology; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006168:Guinea Pigs; D007279:Injections, Subcutaneous; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013003:Somatosensory Cortex / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013501:Surface-Active Agents / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D005456:Fluorescent Dyes; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; D016650:Fluorescein-5-isothiocyanate