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. 2014 Jan 27;9(1):e86472.
doi: 10.1371/journal.pone.0086472. eCollection 2014.

Depletion of brain docosahexaenoic acid impairs recovery from traumatic brain injury

Abhishek Desai  1 , Karl Kevala  1 , Hee-Yong Kim  1
Affiliations

Depletion of brain docosahexaenoic acid impairs recovery from traumatic brain injury

Abhishek Desai et al. PLoS One. .

Abstract

Omega-3 fatty acids are crucial for proper development and function of the brain where docosahexaenoic acid (DHA), the primary omega-3 fatty acid in the brain, is retained avidly by the neuronal membranes. We investigated the effect of DHA depletion in the brain on the outcome of traumatic brain injury (TBI). Pregnant mice were put on an omega-3 fatty acid adequate or deficient diet from gestation day 14 and the pups were raised on the respective diets. Continuation of this dietary regime for three generations resulted in approximately 70% loss of DHA in the brain. Controlled cortical impact was delivered to both groups of mice to produce severe TBI and the functional recovery was compared. Compared to the omega-3 adequate mice, the DHA depleted mice exhibited significantly slower recovery from motor deficits evaluated by the rotarod and the beam walk tests. Furthermore, the DHA deficient mice showed greater anxiety-like behavior tested in the open field test as well as cognitive deficits evaluated by the novel object recognition test. The level of alpha spectrin II breakdown products, the markers of TBI, was significantly elevated in the deficient mouse cortices, indicating that the injury is greater in the deficient brains. This observation was further supported by the reduction of NeuN positive cells around the site of injury in the deficient mice, indicating exacerbated neuronal death after injury. These results suggest an important influence of the brain DHA status on TBI outcome.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Omega-3 fatty acid deficiency impairs recovery from TBI-induced motor deficits.
(A) The rotarod test showing slower recovery from TBI in the DHA deficient group (Deficient TBI) as compared to the adequate (Adequate TBI) mice with statistically significant differences on day 2 and day 4 after TBI (* p<0.05 and *** p<0.001 vs. the respective O-3 adequate group; n = 8). (B) The beam walk test showing greater hindlimb footslips in DHA deficient mice as compared to the respective adequate controls (* p<0.05, ** p<0.01 and *** p<0.001 vs. adequate TBI group; n = 7–8).
Figure 2
Figure 2. DHA depleted mice exhibit greater anxiety-like behavior and post-TBI memory deficits.
(A) DHA deficient (Deficient) mice spend significantly less time in the centre zone of the open field than their DHA adequate (Adequate) counterparts (* p<0.05 vs. Adequate), thus exhibiting anxiety-like behavior. (B) A similar pattern of exploration observed on day 5 after TBI (* p<0.05 vs. Adequate TBI; n = 8). (C) No significant difference observed in novel object exploration time between the non-injured DHA adequate and deficient mice (n = 7). (D) Significantly less exploration of the novel objects in DHA depleted mice on day 7 after TBI than their adequate counterparts (** p<0.01 vs. Adequate TBI; n = 8).
Figure 3
Figure 3. DHA deficiency increases TBI-induced spectrin-αII breakdown products (SBDPs) and decreases synapsin 1.
(A) SBDP levels differentially increased after TBI in the affected cortices of DHA adequate (Ade) and deficient mice (Def). The contralateral cortices were used as controls. The deficient TBI group showed a significantly greater increase in SBDP levels after TBI for both 145 kDa and 150 kDa fragments as compared to the adequate TBI group (n = 4). (B) Synapsin 1 level affected by TBI and DHA depletion. TBI significantly decreased the synapsin-1 level in both diet groups. DHA depletion lowered the synapsin significantly (p<0.05) in the non-injured mouse cortices. Although statistical significance was not reached, a trend of further decrease in synapsin 1 level after TBI was observed with DHA deficiency. * p<0.05; ** p<0.01; *** p<0.001 compared to the non-injured adequate group.
Figure 4
Figure 4. DHA deficiency decreases NeuN positive cells after TBI.
DHA depleted mice showed decreased NeuN positive cells in the peri-contusional cortices relative to the DHA adequate mice as indicated by the representative micrographs (A) and quantitative analysis (B) of 25 brain sections from 5 mice. Scale bar  =  50µm. * p<0.05.
Figure 5
Figure 5. Depletion of DHA does not affect the volume of the lesion induced by TBI.
Lesion volumes of DHA depleted brains after TBI are not statistically different from those of the DHA adequate controls (n = 6).
See this image and copyright information in PMC

References

    1. Faul M, Xu L, Wald MM, Coronado VG (2010) Traumatic Brain Injury in the United States: emergency department visits, hospitalizations and deaths 2002–2006 Atlanta (GA): Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. 7 p.
    1. Xiong Y, Mahmood A, Chopp M (2013) Animal models of traumatic brain injury. Nat Rev Neurosci 14: 128–142. - PMC - PubMed
    1. Simopoulas AP (2011) Evolutionary aspects of diet: The omega-6/omega-3 ratio and the brain. Mol Neurobiol 44: 203–215. - PubMed
    1. Homayoun P, Parkins NE, Soblosky J, Carey ME, Rodriguez de Turco EB, et al. (2000) Cortical impact injury in rats promotes a rapid and sustained increase in polyunsaturated free fatty acids and diacylglycerols. Neurochem Res 25: 269–276. - PubMed
    1. Cao D, Kevala K, Kim J, Moon HS, Jun SB, et al. (2009) Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function. J Neurochem 111: 510–521. - PMC - PubMed

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