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Neuroprotective role of hydralazine in rat spinal cord injury‐attenuation of acrolein‐mediated damage
Author(s) -
Park Jonghyuck,
Zheng Lingxing,
Marquis Andrew,
Walls Michael,
Duerstock Brad,
Pond Amber,
VegaAlvarez Sasha,
Wang He,
Ouyang Zheng,
Shi Riyi
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12628
Subject(s) - acrolein , neuroprotection , hydralazine , spinal cord injury , pharmacology , medicine , spinal cord , lipid peroxidation , anesthesia , chemistry , biochemistry , oxidative stress , psychiatry , blood pressure , catalysis
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.The pathological role of acrolein in spinal cord injury (SCI) is demonstrated through its prolonged elevation and subsequent reduction by hydralazine, an acrolein scavenger, which leads to amelioration of tissue damage, motor deficits, and neuropathic pain. Acrolein injection into the spinal cord caused similar SCI pathologies that further support its role as an effective therapeutic target in SCI.