Dimethylsulfoxide enhances CNS neuronal plasma membrane resealing after injury in low temperature or low calcium.
The inability to repair the damaged membrane may be one of the key mechanisms underlying the severe neuronal degeneration and overall functional loss seen in in vivo spinal cord injury and traumatic axonal injury in blunt head trauma. Promoting membrane resealing following damage may therefore constitute a potential effective therapeutic intervention in treating head trauma and spinal cord injuries. In our previous studies, we have shown that the axolemma failed to reseal following transection in clinically related situations, such as low extracellular calcium and low temperature. Our current studies indicate that DMSO is capable of rendering significant improvement in guinea pig axonal membrane resealing following transection in both 0.5 mM [Ca(2+)](0) and 25 degrees C situations. This was demonstrated physiologically by monitoring membrane potential recovery and anatomically by conducting HRP-exclusion assays 60 minutes after injury. Further, we have shown that the addition of DMSO in normal Krebs' solution (2 mM [Ca(2+)](0) and 37 degrees C) resulted in a decrease in membrane repair following injury. This indicates that DMSO-mediated membrane repair is sensitive to temperature and calcium. This study suggests the role of DMSO in axonal membrane resealing in clinically relevant conditions and raises the possibility of using DMSO in combination with other more established therapies in spinal cord injury treatment.
Shi
R
R
Department of Basic Medical Sciences, Institute for Applied Neurology, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA. riyi@vet.purdue.edu
Qiao
X
X
Emerson
N
N
Malcom
A
A
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism; D001681:Biological Assay; D002118:Calcium / Q000172:deficiency*; D002452:Cell Count; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006735:Horseradish Peroxidase; D007035:Hypothermia / Q000378:metabolism* / Q000503:physiopathology; D007036:Hypothermia, Induced; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016896:Treatment Outcome
D006735:Horseradish Peroxidase; D002118:Calcium; D004121:Dimethyl Sulfoxide