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

We have previously reported in a model of spinal cord injury that the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) has signifi cant neuroprotective effects after trauma in the central nervous system [1]. In the present study we extend our observations on the neuroprotective and neuroregenerative effects of DHA to a peripheral nerve injury model. Facial nerve transection in mice is a well-established model used in studies on axonal regeneration [2]. We carried out this nerve lesion in mice and we studied the effects of oral supplementation with DHA after injury, on neuronal and glial markers of injury, and on neurological outcome. Female adult C57Bl6 mice (6 animals per group) were used throughout. Animals were placed for 1 week before surgery on a standard powdered diet. For the surgery, the right facial nerve, including the retroauricular branch, was transected at the styloid foramen under deep anaesthesia. After injury, mice continued to receive either the standard diet or a diet enriched with DHA (300 mg/kg/day), for 14 days. On the last day of treatment, the neurological outcome was assessed by measuring the movement of the whiskers, on a scale from 0 (no movement) to 3 (normal movement) [3]. Then the animals were killed and perfused intracardially with 4% paraformaldehyde. The brainstem was removed, post-fi xed and cryoprotected. 20 µm sections were cut at the level of the facial nucleus, and were incubated with primary antisera for calcitonin gene-related peptide (CGRP, 1:400, peninsula) and galanin (1:400, Peninsula), as neuronal markers, and for the integrin subunits αM (1:5000, Pharmingen) and β1 (1:3000, Pharmingen), whose expression is microglial only, and mixed neuronal/microglial, respectively. Total immunoreactivity for each antigen was quantifi ed in 2 sections per animal. Data was expressed as means ± SEM and analysed statistically using Student's t test. In the DHA-treated group there was a signifi cant increase in the number of both CGRP-and galanin-immunoreactive sprouts, vs. the lesioned control animals kept on the normal diet (+ 140% and + 90%, respectively, both p < 0.05). A signifi cant increase was also seen in integrin immunoreactivity, with an increase of 20% for the αM-, and 167% for the β1-integrin subunit, respectively (both p < 0.05) in animals receiving the DHA-supplemented diet, in comparison with animals on the control diet. The intake of DHA after injury also led to a better functional outcome, although the increase in whisker mobility 14 days after injury (+ 67% vs. controls) was not statistically signifi cant. These results show that the dietary supplementation with DHA in the period following facial nerve injury has significant effects on the response of both neurons and microglia to injury, and appears to promote a pro-regenerative response. This suggests that DHA could have a neuroprotective potential in the treatment of peripheral nerve injury.

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supporting

confidence: 66%

Effect of docosahexaenoic acid in a mouse facial nerve injury model

Makwana

Dyall

Raivich

et al. 2007

OCL

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“…In a rat model of SCI Omega-3 PUF was found to be neuroprotective and omega-6 PUFAs had a damaging effect after SCI in the adult rat. 106 Nigella sativa (NS) In a rat model of SCI NS treatment is beneficial in spinal cord tissue damage through reducing oxidative stress. 107 Oxidative stress in spinal cord injury Z Jia et al that D3T increases multiple cellular antioxidants including glutathione and NQO1, two crucial cellular defenses against oxidative and electrophilic stress in human neuroblastoma cells (SH-SY5Y), human primary neurons and astrocytes, suggesting that D3T-mediated antioxidant induction is not cell-type specific.…”

Section: Nucleusmentioning

confidence: 99%

Oxidative stress in spinal cord injury and antioxidant-based intervention

Jia

Zhu

Li³

et al. 2011

Spinal Cord

265

176

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Study design: Literature review. Objectives: Spinal cord injury (SCI) remains a major public health issue in developed countries as well as worldwide. The pathophysiology of SCI is characterized by an initial primary injury followed by secondary deterioration. Although the etiology and pathogenesis of SCI remain to be fully understood, it has been suggested that reactive oxygen species (ROS) and oxidative stress have a significant role in the pathophysiology of SCI. Thus, alleviating oxidative stress may be an effective strategy for therapeutic intervention of SCI. The aim of this review was to describe (i) the sources of ROS as well as the major antioxidant defenses with particular attention being paid to lipid peroxidation; (ii) the biomarkers of oxidative stress in SCI and (iii) the neuroprotective effects of various compounds with antioxidative properties in animal models of SCI. Methods: PubMed, one of the most comprehensive biomedical databases, was searched from 1976-2011. All relevant papers were read by title, abstract and full-length article. Results: Oxidative stress is considered a hallmark of injury of SCI. Thus, alleviating oxidative stress may be an effective way of therapeutic intervention of SCI. Two of these agents, the glucocorticoid steroid methylprednisolone and the non-glucocorticoid 21-aminosteroid tirilazad, have been shown to possess significant antioxidant activities and improve recovery of SCI patients in clinical trials. Other promising botanical compounds and their molecular targets and mechanisms of action with regard to potential protection against SCI were also described. These include carotenoids and phenolic compounds. Conclusion: ROS and oxidative stress have a significant role in the pathophysiology of SCI. Alleviating oxidative stress is be an effective strategy for therapeutic intervention of SCI. Extensive research over the past several decades has identified numerous bioactive compounds that have antioxidative stress benefits in animal models of SCI. Thus, continued studies on bioactive compounds with ROS-scavenging capacity may lead to the development of effective antioxidant-based modalities for treating SCI in human subjects.

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…Although no specific report of precise incidence of SCI could be found in Iran, a recent study revealed the prevalence of SCI in Tehran, which currently stands at 1.2-11.4 per 10 000 people. 3 Recently, some reports have supported the positive effect of omega-3 polyunsaturated fatty acids (o-3 PUFAs) in induction of neurorecovery, 4,5 which is mediated through its antioxidant and anti-inflammatory effects. 6 PUFAs are important components of phospholipids which contribute in constitution of cell membrane.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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Study design: A double-blinded randomized clinical trial. Objectives: The anti-inflammatory and neuroprotective effect of omega-3 fatty acids have been shown so far, but still its influence on clinical measures in spinal cord-injured human models were not known. We tried to investigate changes in disability and dependency scores in chronic traumatic spinal cord-injured patients after 14 months of o-3 fatty-acid consumption. Methods: Main inclusion criteria were: traumatic spinal cord injury (SCI) and post injury duration longer than 1 year. Disability and dependency was assessed using UK Functional Independence Measure and Functional Assessment Measure (FIM þ FAM) scale. MorDHA capsules (435 mg of docosahexaenoic acid and 65 mg of eicosapentaenoic acid) were administered in treatment group, whereas control group received placebo capsules for 14 months. UK FIM þ FAM scale were estimated before intervention and at the end of the trial. Results: Fifty-four patients in treatment group and 50 patients in placebo group completed the trial. Highest scores were detected in cognitive domain in both groups before and after intervention. Most dependency was observed in locomotion subscale and secondly in sphincter control. Scores of none of these components were changed by o-3 fatty-acid consumption. Conclusion: Although omega-3 fatty acids have been shown to have neuroprotective effect in acute phase of SCI, it seems that they have no significant influence in chronic inflammatory state of SCI. The positive effect of o-3 fatty acid in chronic neurorecovery process, if exists, is weaker to exert any significant improvement in UK FIM þ FAM scores in spinal cord-injured individuals.

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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

Cited by 189 publications

References 47 publications

Effect of docosahexaenoic acid in a mouse facial nerve injury model

Effect of docosahexaenoic acid in a mouse facial nerve injury model

Oxidative stress in spinal cord injury and antioxidant-based intervention

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

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