Polyethylene glycol enhances axolemmal resealing following transection in cultured cells and in ex vivo spinal cord.
The integrity of the neuronal membrane is critical for its function as well as survival, and ineffective repair of damaged membranes may be one of the key factors underlying the neuronal degeneration and overall functional loss that occurs after spinal cord injury and traumatic brain injury. Previously, we showed that polyethylene glycol (PEG) can reseal axonal membranes following compression in isolated guinea pig spinal cord white matter. We now report that 10 mM PEG can also significantly enhance membrane resealing following transection in the clinically relevant conditions of low extracellular Ca(2+) and low temperature. Such beneficial effects were demonstrated both functionally, through membrane potential measured by double sucrose gap apparatus, and anatomically, through horseradish peroxidase and tetramethyl rhodamine dextran dye exclusion assays. We further noted that axons with small diameters preferentially benefited from PEG-mediated axolemmal resealing. Using atomic force microscopy, we further showed that PEG can effectively reduce neuronal membrane surface tension. We hypothesize that PEG may promote axolemmal resealing by increasing membrane line tension and reducing membrane tension, thus creating conditions more favorable to membrane resealing. In summary, these studies suggest that PEG is effective under the clinically relevant conditions of low Ca(2+) and temperature, and thus has the potential to be used in combination with other more established interventions in spinal cord and traumatic brain injury.
Nehrt
Ashley
A
Center for Paralysis Research, Department of Basic Medical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, Indiana 47907-1244, USA.
Hamann
Kristin
K
Ouyang
Hui
H
Shi
Riyi
R
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D001831:Body Temperature; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D003080:Cold Temperature; D005260:Female; D006168:Guinea Pigs; D007036:Hypothermia, Induced; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009924:Organ Culture Techniques; D011092:Polyethylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D012997:Solvents / Q000494:pharmacology / Q000627:therapeutic use; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013500:Surface Tension / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D018696:Neuroprotective Agents; D012997:Solvents; D011092:Polyethylene Glycols; D002118:Calcium