title: Neuroprotective role of hydralazine in rat spinal cord injury-attenuation of acrolein-mediated damage.
abstract: Acrolein, an α,β-unsaturated aldehyde and a reactive product of lipid peroxidation, has been suggested as a key factor in neural post-traumatic secondary injury in spinal cord injury (SCI), mainly based on in vitro and ex vivo evidence. Here, we demonstrate an increase of acrolein up to 300%; the elevation lasted at least 2 weeks in a rat SCI model. More importantly, hydralazine, a known acrolein scavenger can provide neuroprotection when applied systemically. Besides effectively reducing acrolein, hydralazine treatment also resulted in significant amelioration of tissue damage, motor deficits, and neuropathic pain. This effect was further supported by demonstrating the ability of hydralazine to reach spinal cord tissue at a therapeutic level following intraperitoneal application. This suggests that hydralazine is an effective neuroprotective agent not only in vitro, but in a live animal model of SCI as well. Finally, the role of acrolein in SCI was further validated by the fact that acrolein injection into the spinal cord caused significant SCI-like tissue damage and motor deficits. Taken together, available evidence strongly suggests a critical causal role of acrolein in the pathogenesis of spinal cord trauma. Since acrolein has been linked to a variety of illness and conditions, we believe that acrolein-scavenging measures have the potential to be expanded significantly ensuring a broad impact on human health.
authors.affiliation: Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA.
authors.forename: Jonghyuck
authors.initials: J
authors.lastname: Park
authors.forename: Lingxing
authors.initials: L
authors.lastname: Zheng
authors.forename: Andrew
authors.initials: A
authors.lastname: Marquis
authors.forename: Michael
authors.initials: M
authors.lastname: Walls
authors.forename: Brad
authors.initials: B
authors.lastname: Duerstock
authors.forename: Amber
authors.initials: A
authors.lastname: Pond
authors.forename: Sasha
authors.initials: S
authors.lastname: Vega-Alvarez
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ouyang
authors.forename: Riyi
authors.initials: R
authors.lastname: Shi
mesh_terms: D000171:Acrolein / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D003288:Contusions / Q000188:drug therapy / Q000473:pathology; D006830:Hydralazine / Q000493:pharmacokinetics / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009437:Neuralgia / Q000517:prevention & control; D018696:Neuroprotective Agents; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology
chemical_list: D018696:Neuroprotective Agents; D006830:Hydralazine; D000171:Acrolein
keywords: acrolein scavenger; aldehyde; lipid peroxidation; oxidative stress