Docosahexaenoic acid prevents white matter damage after spinal cord injury.
We have previously shown that the omega-3 fatty acid docosahexaenoic acid (DHA) significantly improves several histological and behavioral measures after spinal cord injury (SCI). White matter damage plays a key role in neurological outcome following SCI. Therefore, we examined the effects of the acute intravenous (IV) administration of DHA (250 nmol/kg) 30 min after thoracic compression SCI in rats, alone or in combination with a DHA-enriched diet (400 mg/kg/d, administered for 6 weeks post-injury), on white matter pathology. By 1 week post-injury, the acute IV DHA injection led to significantly reduced axonal dysfunction, as indicated by accumulation of β-amyloid precursor protein (-55% compared to vehicle-injected controls) in the dorsal columns. The loss of cytoskeletal proteins following SCI was also significantly reduced. There were 43% and 73% more axons immunoreactive for non-phosphorylated 200-kD neurofilament in the ventral white matter and ventrolateral white matter, respectively, in animals receiving DHA injections than vehicle-injected rats. The acute DHA treatment also led to a significant improvement in microtubule-associated protein-2 immunoreactivity. By 6 weeks, damage to myelin and serotonergic fibers was also reduced. For some of the parameters measured, the combination of DHA injection and DHA-enriched diet led to greater neuroprotection than DHA injection alone. These findings demonstrate the therapeutic potential of DHA in SCI, and clearly indicate that this fatty acid confers significant protection to the white matter.
Ward
Rachael E
RE
Centre for Neuroscience and Trauma, The Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom. rachael.ward@ucl.ac.uk
Huang
Wenlong
W
Curran
Olympia E
OE
Priestley
John V
JV
Michael-Titus
Adina T
AT
D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004281:Docosahexaenoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D008869:Microtubule-Associated Proteins; D004281:Docosahexaenoic Acids