Research On The Therapeutic Effect Of Anti-acrolein Drug Of Phenelzine For Spinal Cord Injury

Effective treatment for spinal cord injury(SCI)was a refractory problem worldwide while oxidative stress and lipid peroxidation are believed to play critical role during this injury.Acrolein,an ?,?-unsaturated aldehyde,is the byproduct of oxidative stress lipid peroxidation.It has the ability to damage the biomolecules,such as protein,DNA and lipids.Therefore,more and more evidence suggested acrolein is tremendous deleterious for spinal cord.In this study,contusive spinal cord injury resulted in extreme increase of acrolein in spinal cord and the whole body in concomitant with post-SCI neuropathic pian,motor dysfunction and neural tissue damage.However,the intraperitoneal treatment of phenelzine,an acrolein scavenger,was capable of ameliorating the acute,delayed and chronic post-SCI neuropathic pain,improving the motor function and attenuating the neural tissue damage.Furthermore,the probable mechanism that acrolein contributed to the neuropathic pain was the over-expression of TRPA1 channel in skin,DRG and dorsal horn and phenelzine was able to suppress the over-expression of TRPA1 via eliminating the acrolein.All of these results delineated that the strategy to eliminate the acrolein will be definitely effective for SCI treatment.Finally,two acrolein-scavenger drugs—phenelzine and hydralazine were proved to have almost the same therapeutic effects and pharmacokinetics,suggesting that both of them are promising candidates for treatment of spinal cord injury.Moreover,the neuropathic pain and neurons damage was observed in concomitant with the increased of acrolein dramatically in spinal cord and the whole body after ischemic-reperfusion spinal cord injury.Nevertheless,phenelzine treatment significantly eliminated the acrolein,thus further leading to the amelioration of the neuropathic pain and the preservation of the neurons in Gray Matter.Overall,acrolein plays essential roles in SCI,indicating as the damage to neural tissues,impairing motor function and eliciting neuropathic pain.Therefore,the acrolein scavenger drug of phenelzine will be useful for preventing the damage caused by acrolein and thus be effective for treatment of patients with SCI.