Omega-3 fatty acids improve recovery, whereas omega-6 fatty acids worsen outcome, after spinal cord injury in the adult rat.
Spinal cord injury (SCI) is a cause of major neurological disability, and no satisfactory treatment is currently available. Evidence suggests that polyunsaturated fatty acids (PUFAs) could target some of the pathological mechanisms that underlie damage after SCI. We examined the effects of treatment with PUFAs after lateral spinal cord hemisection in the rat. The omega-3 PUFAs alpha-linolenic acid and docosahexaenoic acid (DHA) injected 30 min after injury induced significantly improved locomotor performance and neuroprotection, including decreased lesion size and apoptosis and increased neuronal and oligodendrocyte survival. Evidence showing a decrease in RNA/DNA oxidation suggests that the neuroprotective effect of omega-3 PUFAs involved a significant antioxidant function. In contrast, animals treated with arachidonic acid, an omega-6 PUFA, had a significantly worse outcome than controls. We confirmed the neuroprotective effect of omega-3 PUFAs by examining the effects of DHA treatment after spinal cord compression injury. Results indicated that DHA administered 30 min after spinal cord compression not only greatly increased survival of neurons but also resulted in significantly better locomotor performance for up to 6 weeks after injury. This report shows a striking difference in efficacy between the effects of treatment with omega-3 and omega-6 PUFAs on the outcome of SCI, with omega-3 PUFAs being neuroprotective and omega-6 PUFAs having a damaging effect. Given the proven clinical safety of omega-3 PUFAs, our observations show that these PUFAs have significant therapeutic potential in SCI. In contrast, the use of preparations enriched in omega-6 PUFAs after injury could worsen outcome after SCI.
King
Von R
VR
Institute of Cell and Molecular Science, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, United Kingdom. vonrking@yahoo.co.uk
Huang
Wenlong L
WL
Dyall
Simon C
SC
Curran
Olimpia E
OE
Priestley
John V
JV
Michael-Titus
Adina T
AT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016718:Arachidonic Acid / Q000008:administration & dosage; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000008:administration & dosage; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage*; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D016896:Treatment Outcome; D017962:alpha-Linolenic Acid / Q000008:administration & dosage
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D018696:Neuroprotective Agents; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid