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.

Dietary Omega-3 Polyunsaturated Fatty Acids Improve the Neurolipidome and Restore the DHA Status while Promoting Functional Recovery after Experimental Spinal Cord Injury

“…We recently reported that acute parenteral administration of DHA before injury leads to early improvements in conduction and locomotor function after SCI. 22 This finding is consistent with studies showing the efficacy of x-3 PUFAs as a post-treatment modality to ameliorate secondary damage and dysfunction. 12,[17][18][19][20][21][22][23][24] There is still a significant gap in our knowledge, however, concerning the therapeutic effects of prophylactic x-3 PUFAs against neurotrama.…”

“…[12][13][14][15][16] In contrast, x-3 PUFAs, such as DHA, are anti-inflammatory, confer neuroprotection, and play significant roles in facilitating functional recovery in various SCI animal models. 12,[17][18][19][20][21][22] One important hypothesis arising from our work and from other published epidemiological evidence is that dietary x-3 PUFAs can confer resiliency and facilitate recovery, even when administered before SCI. We recently reported that acute parenteral administration of DHA before injury leads to early improvements in conduction and locomotor function after SCI.…”

Astrocytes Release Polyunsaturated Fatty Acids by Lipopolysaccharide Stimuli

“…[20][21][22] As previously reported, essential n-3 PUFAs, especially DHA, have beneficial actions in many inflammatory diseases. [23][24][25][26] For example, in inflamed tissues at peripheral sites, DHA is released from immune cells such as neutrophils during the acute phase of the inflammatory process. 27) Most important thing in this study is that LPS stimulation specifically facilitated the release of DHA and ARA from astrocytes although SFAs did not change.…”

N-3 PUFAs and neuroinflammatory processes in cognitive disorders

“…The anti-inflammatory activity of DHA could also derive from its direct effect on invading macrophages or microglia. Both in vitro and in vivo data highlight that DHA blocks invading macrophages and microglia activation and the signalling pathway (NF-kB) in the brain and spinal cord of several inflammatory rodents models (De Smedt-Peyrusse et al, 2008;Figueroa et al, 2012;Lim et al, 2013;Lu et al, 2013). Recent data highlight that in vitro DHA has not only anti-inflammatory activity but also promotes microglia to a M2 phenotype with increased Aβ42 phagocytosis (Hjorth et al, 2013).…”