title: Improved outcome after spinal cord compression injury in mice treated with docosahexaenoic acid.
abstract: In this study we have characterised the locomotor recovery, and temporal profile of cell loss, in a novel thoracic compression spinal cord injury (SCI) in the mouse. We have also shown that treatment with docosahexaenoic acid (DHA) is neuroprotective in this model of SCI, strengthening the growing literature demonstrating that omega-3 polyunsaturated fatty acids are neuroprotective after SCI. Compression SCI in C57BL/6 mice was produced by placing a 10 g weight for 5 min onto a 2 mm × 1.5 mm platform applied to the dura at vertebral level T12. Mice partly recovered from complete hindlimb paralysis and by 28 days post-surgery had plateaued at an average BMS locomotor score of 4.2, equivalent to weight support with plantar stepping. During the same period, neuronal loss at the epicentre increased from 26% of ventral horn neurons by day 1, to 68% by day 28. Delayed loss of oligodendrocytes was also seen (e.g. 84% by day 28 in the dorsal columns) and microglia/macrophage activation was maximal at 7 days. In contrast, axonal damage, judged by a decrease in the non-phosphorylated form of 200 kD neurofilament, was an early event, as the loss was seen by day 1 and did not change markedly over time. Mice that received an intravenous (i.v.) injection of 500 nmol/kg DHA 30 min after SCI, showed improved locomotor recovery and, at 28 day survival, reduced neuronal, oligodendrocyte and neurofilament loss, and reduced microglia/macrophage activation. For some of these indices of SCI, enrichment of the diet with 400 mg/kg/day DHA led to further improvement. However, dietary DHA supplementation, without the initial i.v. injection, was ineffective.
authors.affiliation: Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Siew-Na
authors.initials: SN
authors.lastname: Lim
authors.forename: Wenlong
authors.initials: W
authors.lastname: Huang
authors.forename: Jodie C E
authors.initials: JC
authors.lastname: Hall
authors.forename: Adina T
authors.initials: AT
authors.lastname: Michael-Titus
authors.forename: John V
authors.initials: JV
authors.lastname: Priestley
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004032:Diet; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D008124:Locomotion / Q000502:physiology; D008262:Macrophage Activation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000473:pathology; D009836:Oligodendroglia / Q000473:pathology; D010243:Paralysis / Q000188:drug therapy / Q000209:etiology; D020127:Recovery of Function; D013117:Spinal Cord Compression / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D016900:Neurofilament Proteins; D004281:Docosahexaenoic Acids