Lipid peroxidation-derived aldehydes, such as acrolein, the most reactive aldehyde, have emerged as key culprits in sustaining post-spinal cord injury (SCI) secondary pathologies leading to functional loss. Strong evidence suggests that mitochondrial aldehyde dehydrogenase-2 (ALDH2), a key oxidoreductase and powerful endogenous anti-aldehyde machinery, is likely important for protecting neurons from aldehydes-mediated degeneration. Using a rat model of spinal cord contusion injury and recently discovered ALDH2 activator (Alda-1), we planned to validate the aldehyde-clearing and neuroprotective role of ALDH2. Over an acute 2 day period post injury, we found that ALDH2 expression was significantly lowered post-SCI, but not so in rats given Alda-1. This lower enzymatic expression may be linked to heightened acrolein- ALDH2 adduction, which was revealed in co-immunoprecipitation experiments. We have also found that administration of Alda-1 to SCI rats significantly lowered acrolein in the spinal cord, and reduced cyst pathology. In addition, Alda-1 treatment also resulted in significant improvement of motor function and attenuated post-SCI mechanical hypersensitivity up to 28 days post-SCI. Finally, ALDH2 was found to play a critical role in in vitro protection of PC12 cells from acrolein exposure. It is expected that the outcome of this study will broaden and enhance anti-aldehyde strategies in combating post-SCI neurodegeneration and potentially bring treatment to millions of SCI victims. All animal work was approved by Purdue Animal Care and Use Committee (approval No. 1111000095) on January 1, 2021.

Seth A.Herr;Liangqin Shi;Thomas Gianaris;Yucheng Jiao;Siyuan Sun;Nick Race;Scott Shapiro;Riyi Shi

Center for Paralysis Research&Department of Basic Medical Sciences,College of Veterinary Medicine,Purdue University,West Lafayette,IN,USA;Department of Orthopedics,Ruijin Hospital,School of Medicine,Shanghai Jiaotong University,Institute of Trauma and Orthopedics,Shanghai,China;Department of Neurological Surgery,Indiana University School of Medicine,Indianapolis,IN,USA

中国神经再生研究（英文版）

[1]Seth A.Herr;Liangqin Shi;Thomas Gianaris;Yucheng Jiao;Siyuan Sun;Nick Race;Scott Shapiro;Riyi Shi-.Critical role of mitochondrial aldehyde dehydrogenase 2 in acrolein sequestering in rat spinal cord injury)[J].中国神经再生研究（英文版）,2022(07):1505-1511

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