title: Unilateral microinjection of acrolein into thoracic spinal cord produces acute and chronic injury and functional deficits.
abstract: Although lipid peroxidation has long been associated with spinal cord injury (SCI), the specific role of lipid peroxidation-derived byproducts such as acrolein in mediating damage remains to be fully understood. Acrolein, an α-β unsaturated aldehyde, is highly reactive with proteins, DNA, and phospholipids and is considered as a second toxic messenger that disseminates and augments initial free radical events. Previously, we showed that acrolein increased following traumatic SCI and injection of acrolein induced tissue damage. Here, we demonstrate that microinjection of acrolein into the thoracic spinal cord of adult rats resulted in dose-dependent tissue damage and functional deficits. At 24h (acute) after the microinjection, tissue damage, motoneuron loss, and spinal cord swelling were observed on sections stained with Cresyl Violet. Luxol fast blue staining further showed that acrolein injection resulted in dose-dependent demyelination. At 8weeks (chronic) after the microinjection, cord shrinkage, astrocyte activation, and macrophage infiltration were observed along with tissue damage, neuron loss, and demyelination. These pathological changes resulted in behavioral impairments as measured by both the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and grid walking analysis. Electron microscopy further demonstrated that acrolein induced axonal degeneration, demyelination, and macrophage infiltration. These results, combined with our previous reports, strongly suggest that acrolein may play a critical causal role in the pathogenesis of SCI and that targeting acrolein could be an attractive strategy for repair after SCI.
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery & Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, United States. Electronic address: redgianaris@gmail.com.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gianaris
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery & Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, United States. Electronic address: nailiu@iupui.edu.
authors.forename: Nai-Kui
authors.initials: NK
authors.lastname: Liu
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery & Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, United States. Electronic address: ntwxf001@163.com.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Wang
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery & Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, United States. Electronic address: racer12b@gmail.com.
authors.forename: Eddie
authors.initials: E
authors.lastname: Oakes
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery & Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, United States. Electronic address: jbrenia@iupui.edu.
authors.forename: John
authors.initials: J
authors.lastname: Brenia
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery & Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, United States. Electronic address: tgianari@iupui.edu.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gianaris
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery & Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, United States. Electronic address: yiwenruan@yahoo.com.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery & Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, United States. Electronic address: dengl@iupui.edu.
authors.forename: Ling-Xiao
authors.initials: LX
authors.lastname: Deng
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery & Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, United States. Electronic address: mariagoetz1@gmail.com.
authors.forename: Maria
authors.initials: M
authors.lastname: Goetz
authors.affiliation: Department of Basic Medical Sciences, College of Veterinary Medicine and Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, United States. Electronic address: saschavega@gmail.com.
authors.forename: Sasha
authors.initials: S
authors.lastname: Vega-Alvarez
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery & Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, United States. Electronic address: qilu@iupui.edu.
authors.forename: Qing-Bo
authors.initials: QB
authors.lastname: Lu
authors.affiliation: Department of Basic Medical Sciences, College of Veterinary Medicine and Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, United States. Electronic address: shir@purdue.edu.
authors.forename: Riyi
authors.initials: R
authors.lastname: Shi
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery & Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, United States. Electronic address: xu26@iupui.edu.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Xu
mesh_terms: D000171:Acrolein / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001369:Axons / Q000187:drug effects / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D005260:Female; D008124:Locomotion / Q000187:drug effects*; D009186:Myelin Sheath / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000139:chemically induced* / Q000473:pathology*
chemical_list: D000171:Acrolein
keywords: acrolein; aldehyde; lipid peroxidation; oxidative stress; spinal cord injury