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 10g weight for 5min onto a 2mm×1.5mm platform applied to the dura at vertebral level T12. Mice partly recovered from complete hindlimb paralysis and by 28days 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 7days. In contrast, axonal damage, judged by a decrease in the non-phosphorylated form of 200kD 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 500nmol/kg DHA 30min after SCI, showed improved locomotor recovery and, at 28day survival, reduced neuronal, oligodendrocyte and neurofilament loss, and reduced microglia/macrophage activation. For some of these indices of SCI, enrichment of the diet with 400mg/kg/day DHA led to further improvement. However, dietary DHA supplementation, without the initial i.v. injection, was ineffective.