Polyethylene glycol improves function and reduces oxidative stress in synaptosomal preparations following spinal cord injury.
Spinal cord injury (SCI) results in rapid and significant oxidative stress. We have previously demonstrated that administration of polyethylene glycol (PEG) inhibits oxidative stress using an in vitro model of SCI. In this study we tested the effects of PEG in vivo, to elucidate the mechanism of PEG-mediated neuroprotection. We show that a compression injury at T10-11 induced diffusive oxidative stress in crude synaptosomal preparations, correlated with synaptosomal dysfunction and increased intrasynaptosomal calcium. Administration of PEG immediately post-injury produced a marked decrease in synaptosomal oxidative stress and calcium, associated with an increase in synaptosomal function. Confocal microscopy using fluorescein conjugated PEG revealed that PEG entered the cells of the injured spinal cord, placing the polymer in a position to directly interact with cellular organelles. PEG attenuates calcium-induced functional compromise of normal spinal cord synaptosomes and mitochondria in vitro. These results indicate that PEG may exert its neuroprotective effect through direct interaction with mitochondria, besides its known ability to rescue neurons and their axons by repairing the plasma membranes. We submit that PEG is likely to interfere with the cascade of secondary injury by several mechanisms of action that in concert reduce oxidative stress.
Department of Basic Medical Sciences, Institute for Applied Neurology, Center for Paralysis Research, Purdue University, West Lafayette, Indiana 47907, USA.
Jian
J
Luo
Richard
R
Borgens
Riyi
R
Shi
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010539:Permeability / Q000187:drug effects; D011092:Polyethylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D016896:Treatment Outcome
D011092:Polyethylene Glycols; D002118:Calcium