Protective effect of chronic ethyl docosahexaenoate administration on brain injury in ischemic gerbils

Cao, Dehua; Xu, Jianfeng; Xue, Rongjian; Zheng, Wenhua; Liu, Zhili

doi:10.1016/j.pbb.2004.09.016

Cited by 70 publications

(42 citation statements)

References 48 publications

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“…Together, our data suggest that -3 PUFAs have significant therapeutic potential in SCI and are consistent with results with these PUFAs in other models of CNS injury (Blondeau et al, 2002;Cao et al, 2004;Zararsiz et al, 2005). However, some issues deserve additional investigation.…”

Section: Discussionsupporting

confidence: 87%

“…AA-treated animals (F ) had fewer oligodendrocytes than the other groups. Scale bar: (in A) A-F, 250 m. models of neurotoxicity (Zararsiz et al, 2005) and forebrain ischemia (Blondeau et al, 2002;Cao et al, 2004) but also attenuate decreases in the CNS levels of antioxidant enzymes (e.g., catalase, superoxide dismutase, and glutathione peroxidase) in these models. To more clearly address the antioxidant role of DHA treatment, studies in our laboratory examining the effects of DHA treatment after spinal cord injury on both lipid peroxidation and protein oxidation are currently underway.…”

Section: Discussionmentioning

confidence: 99%

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Omega-3 Fatty Acids Improve Recovery, whereas Omega-6 Fatty Acids Worsen Outcome, after Spinal Cord Injury in the Adult Rat

King

Huang²,

Dyall³

et al. 2006

J. Neurosci.

189

130

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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 -3 PUFAs ␣-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 -3 PUFAs involved a significant antioxidant function. In contrast, animals treated with arachidonic acid, an -6 PUFA, had a significantly worse outcome than controls. We confirmed the neuroprotective effect of -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 -3 and -6 PUFAs on the outcome of SCI, with -3 PUFAs being neuroprotective and -6 PUFAs having a damaging effect. Given the proven clinical safety of -3 PUFAs, our observations show that these PUFAs have significant therapeutic potential in SCI. In contrast, the use of preparations enriched in -6 PUFAs after injury could worsen outcome after SCI.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Omega-3 Fatty Acids Improve Recovery, whereas Omega-6 Fatty Acids Worsen Outcome, after Spinal Cord Injury in the Adult Rat

King

Huang²,

Dyall³

et al. 2006

J. Neurosci.

189

130

View full text Add to dashboard Cite

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“…The increased susceptibility to cell death in DHA-deficient neurons, where PS was reduced, is consistent with the PS-dependent protection by DHA against neuronal apoptosis observed in Neuro 2A cells. Similarly, it has been demonstrated that DHA supplementation prevented hippocampal cell death induced by ischemia-reperfusion in an animal model (Cao et al, 2004). However, it still remains to be tested whether this in vivo protection against hippocampal cell death by DHA is consistent with the PS-dependent protective effect of DHA on neuronal survival demonstrated in our study using cells in culture.…”

Section: Neuronal Cell Death Promoted By In Vivo Dha Depletionsupporting

confidence: 87%

Biochemical and biological functions of docosahexaenoic acid in the nervous system: modulation by ethanol

Kim

2008

Chemistry and Physics of Lipids

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Docosahexaenoic acid (DHA, 22:6n-3), an n-3 fatty acid highly concentrated in the central nervous system, is essential for proper neuronal and retinal function. While a high level of DHA is generally maintained in neuronal membranes, inadequate supply of n-3 fatty acid or ethanol exposure leads to a significant loss of DHA in neuronal cells. The roles of DHA in neuronal signaling have been emerging. In this review, biological, biochemical and molecular mechanisms supporting the essential function of DHA in neuronal survival and development are described in relation to n-3 fatty acid depleting conditions.

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“…Phopsholipase A2 releases unesterified DHA, which is further metabolized to docosanoids, of which neuroprotectin D1 is a potent inhibitor of oxidative stress induced apoptosis and cyclo-oxygenase 2 (24). Consistent with this role, recent studies have shown that DHA has important free radical scavenging properties and protects against peroxidative damage of lipids and proteins in developing and adult brains, with attenuation of neuron loss and cognitive and locomotor deficits in animal models of ischemia-reperfusion brain injury (36)(37)(38).…”

Section: Introductionmentioning

confidence: 75%

Dietary (n-3) Fatty Acids and Brain Development1

Innis

2007

The Journal of Nutrition

735

512

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Protective effect of chronic ethyl docosahexaenoate administration on brain injury in ischemic gerbils

Cited by 70 publications

References 48 publications

Omega-3 Fatty Acids Improve Recovery, whereas Omega-6 Fatty Acids Worsen Outcome, after Spinal Cord Injury in the Adult Rat

Omega-3 Fatty Acids Improve Recovery, whereas Omega-6 Fatty Acids Worsen Outcome, after Spinal Cord Injury in the Adult Rat

Biochemical and biological functions of docosahexaenoic acid in the nervous system: modulation by ethanol

Dietary (n-3) Fatty Acids and Brain Development1

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