title: Intrathecal Acetyl-L-Carnitine Protects Tissue and Improves Function after a Mild Contusive Spinal Cord Injury in Rats.
abstract: Primary and secondary ischemia after spinal cord injury (SCI) contributes to tissue and axon degeneration, which may result from decreased energy substrate availability for cellular and axonal mitochondrial adenosine triphosphate (ATP) production. Therefore, providing spinal tissue with an alternative energy substrate during ischemia may be neuroprotective after SCI. To assess this, rats received a mild contusive SCI (120 kdyn, Infinite Horizons impactor) at thoracic level 9 (T9), which causes loss of ∼ 80% of the ascending sensory dorsal column axonal projections to the gracile nucleus. Immediately afterwards, the energy substrate acetyl-L-carnitine (ALC; 1 mg/day) or phosphate-buffered saline (PBS) was infused intrathecally (sub-arachnoid) for 6 days via an L5/6 catheter attached to a subcutaneous Alzet pump. ALC treatment improved overground locomotor function (Basso-Beattie-Breshnahan [BBB] score 18 vs. 13) at 6 days, total spared epicenter (71% vs. 57%) and penumbra white matter (90% vs. 85%), ventral penumbra microvessels (108% vs. 79%), and penumbra motor neurons (42% vs. 15%) at 15 days post-SCI, compared with PBS treatment. However, the ascending sensory projections (anterogradely traced with cholera toxin B from the sciatic nerves) and dorsal column white matter and perfused blood vessels were not protected. Furthermore, grid walking, a task we have shown to be dependent on dorsal column function, was not improved. Thus, mitochondrial substrate replacement may only be efficacious in areas of lesser or temporary ischemia, such as the ventral spinal cord and injury penumbra in this study. The current data also support our previous evidence that microvessel loss is central to secondary tissue degeneration.
authors.affiliation: Kentucky Spinal Cord Injury Research Center and Department of Neurological Surgery, University of Louisville , Louisville, Kentucky.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Ewan
authors.affiliation: Kentucky Spinal Cord Injury Research Center and Department of Neurological Surgery, University of Louisville , Louisville, Kentucky.
authors.forename: Theo
authors.initials: T
authors.lastname: Hagg
mesh_terms: D000108:Acetylcarnitine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D060186:Infusions, Spinal; D009043:Motor Activity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D013904:Thoracic Vertebrae; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D014803:Vitamin B Complex; D000108:Acetylcarnitine
keywords: ALC; axon; contusion; dorsal column; ischemia; mitochondria; spinal cord injury