A combination of intravenous and dietary docosahexaenoic acid significantly improves outcome after spinal cord injury

Abstract

Previous studies have shown that omega-3 polyunsaturated fatty acids such as alpha-linolenic acid and docosahexaenoic acid (DHA) are neuroprotective in models of spinal cord injury (SCI) in rodents. However, the mechanism of action underlying these effects has not been elucidated, and the optimum treatment regime remains to be defined. We have therefore carried out a detailed analysis of the effects of DHA in adult rats subject to thoracic compression SCI. Saline or DHA (250 nmol/kg) was administered intravenously (i.v.) 30 min after compression. After injury, the saline group received a standard control diet for 1 or 6 weeks, whereas DHA-injected animals received either a control or a DHA-enriched diet (400 mg/kg/day) for 1 or 6 weeks. Other groups received a DHA-enriched diet only for 1 week following injury, or received acute DHA (250 nmol/kg; i.v.) treatment delayed up to 3 h after injury. We also assessed oxidative stress and the inflammatory reaction at the injury site, neuronal and oligodendrocyte survival and axonal damage and the locomotor recovery. At 24 h, lipid peroxidation, protein oxidation, RNA/DNA oxidation and the induction of cyclooxygenase-2 were all significantly reduced by i.v. DHA administration. At 1 week and 6 weeks, macrophage recruitment was reduced and neuronal and oligodendrocyte survival was substantially increased. Axonal injury was reduced at 6 weeks. Locomotor recovery was improved from day 4, and sustained up to 6 weeks. Rats treated with a DHA-enriched diet in addition to the acute DHA injection were not significantly different from the acute DHA-treated animals at 1 week, but at 6 weeks showed additional improvements in both functional and histological outcomes. DHA treatment was ineffective if the acute injection was delayed until 3 h post-injury, or if the DHA was administered for 1 week solely by diet. Our results in a clinically relevant model of SCI show that significant neuroprotection can be obtained by combining an initial acute i.v. injection of DHA with a sustained dietary supplementation. Given that the safety and tolerability of preparations enriched in omega-3 fatty acids is already well-documented, such a combined DHA treatment regime deserves consideration as a very promising approach to SCI management.

Determination of Omega-3/Omega-6 Ratio in Swine Brain Homogenate as an Animal Model for Human Nervous Tissue

“…DHA increases neuronal survival by unknown mechanisms after spinal cord injury. A possible mechanism would be reducing glutamate toxicity, which is released in large quantities especially after traumatic spinal cord injury [18].…”

Progesterone Reduces Secondary Damage, Preserves White Matter, and Improves Locomotor Outcome after Spinal Cord Contusion

“…the reported PROG actions in locomotor outcome, because therapeutical strategies that limit white matter damage and oligodendrocyte death have been shown to improve recovery after SCI, 68,69 and spontaneous functional recovery correlates well with mature oligodendrocyte number in white matter after spinal cord contusion. 70 PROG could have acted directly on oligodendrocytes, or indirectly by modulating the inflammatory environment, because PROG treatment decreases gliosis and cytokine production after spinal cord transection 22 (author unpublished results).…”

Does consumption of polyunsaturated fatty acids influence on neurorehabilitation in traumatic spinal cord-injured individuals? a double-blinded clinical trial

“…12 Its probable positive effects have been shown on Alzheimer's disease 13 and Huntington 14 in human models, however, its effect on acute neural injury such as acute traumatic SCI have been only investigated on experimental laboratory models and have shown promising outcomes. 4,15,16 Previously, neuroprotective effect of omega 3 PUFAs was observed in acute phase of SCI. 4,16,17 Most of these studies support this positive Omega-3 effect on neurorehabilitation A Norouzi Javidan et al effect on experimental animal models, while literatures on human models are so limited.…”

“…4,15,16 Previously, neuroprotective effect of omega 3 PUFAs was observed in acute phase of SCI. 4,16,17 Most of these studies support this positive Omega-3 effect on neurorehabilitation A Norouzi Javidan et al effect on experimental animal models, while literatures on human models are so limited. By considering the proposed mechanisms of o-3 PUFA in induction of neurorecovery, which originate mostly from its anti-oxidative and anti-inflammatory effects, 18 it is expectable to observe noticeable influence in acute phase of injury when these inflammatory reactions are at their peak level.…”