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, leadi ng to a progressive dissolution of the cell or its process. We have shown t hat an artificial sealing of mechanically damaged membranes by topical appl ication of hydrophilic polymers such as polyethylene glycol (PEG) immediate ly 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) re flex in PEG-treated animals. The CTM reflex is a sensorimotor behavior depe ndent on an intact (and identified) white matter tract within the ventrolat eral 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 bloods tream by several routes of administration. Using a fluorescein decorated PE G, we demonstrate that the polymer specifically targets the hemorrhagic con tusion of the adult guinea pig spinal cord when administered through the va sculature, but not intact regions of the spinal cord. A single subcutaneous injection (30% weight by weight in sterile saline) made 6 hr after a stand ardized spinal cord contusion in adult guinea pigs was sufficient to produc e a rapid recovery of SSEP propagation through the lesion in only PEG-treat ed animals, accompanied by a statistically significant recovery of the CTM reflex. These data suggest that parenterally administered PEG may be a nove l treatment for not only spinal injury, but head injury and stroke as well. (C) 2001 Wiley-Liss, Inc.