title: Docosahexaenoic acid pretreatment confers protection and functional improvements after acute spinal cord injury in adult rats.
abstract: Currently, few interventions have been shown to successfully limit the progression of secondary damage events associated with the acute phase of spinal cord injury (SCI). Docosahexaenoic acid (DHA, C22:6 n-3) is neuroprotective when administered following SCI, but its potential as a pretreatment modality has not been addressed. This study used a novel DHA pretreatment experimental paradigm that targets acute cellular and molecular events during the first week after SCI in rats. We found that DHA pretreatment reduced functional deficits during the acute phase of injury, as shown by significant improvements in Basso-Beattie-Bresnahan (BBB) locomotor scores, and the detection of transcranial magnetic motor evoked potentials (tcMMEPs) compared to vehicle-pretreated animals. We demonstrated that, at 7 days post-injury, DHA pretreatment significantly increased the percentage of white matter sparing, and resulted in axonal preservation, compared to the vehicle injections. We found a significant increase in the survival of NG2+, APC+, and NeuN+ cells in the ventrolateral funiculus (VLF), dorsal corticospinal tract (dCST), and ventral horns, respectively. Interestingly, these DHA protective effects were observed despite the lack of inhibition of inflammatory markers for monocytes/macrophages and astrocytes, ED1/OX42 and GFAP, respectively. DHA pretreatment induced levels of Akt and cyclic AMP responsive element binding protein (CREB) mRNA and protein. This study shows for the first time that DHA pretreatment ameliorates functional deficits, and increases tissue sparing and precursor cell survival. Further, our data suggest that DHA-mediated activation of pro-survival/anti-apoptotic pathways may be independent of its anti-inflammatory effects.
authors.affiliation: Center for Health Disparities and Molecular Medicine and Department of Basic Sciences, Loma Linda University, Loma Linda, California, USA.
authors.forename: Johnny D
authors.initials: JD
authors.lastname: Figueroa
authors.forename: Kathia
authors.initials: K
authors.lastname: Cordero
authors.forename: Keisha
authors.initials: K
authors.lastname: Baldeosingh
authors.forename: Aranza I
authors.initials: AI
authors.lastname: Torrado
authors.forename: Robert L
authors.initials: RL
authors.lastname: Walker
authors.forename: Jorge D
authors.initials: JD
authors.lastname: Miranda
authors.forename: Marino De
authors.initials: MD
authors.lastname: Leon
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D019054:Evoked Potentials, Motor / Q000187:drug effects; D005260:Female; D005455:Fluorescent Antibody Technique; D006614:Hindlimb / Q000502:physiology; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000473:pathology; D007275:Injections, Intravenous; D008124:Locomotion / Q000502:physiology; D008262:Macrophage Activation / Q000187:drug effects; D017628:Microglia / Q000187:drug effects; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D009431:Neural Conduction / Q000187:drug effects; D058953:Neural Stem Cells / Q000187:drug effects; D018696:Neuroprotective Agents; D051058:Oncogene Protein v-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000473:pathology / Q000517:prevention & control*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D018696:Neuroprotective Agents; D004281:Docosahexaenoic Acids; D051058:Oncogene Protein v-akt