Omega-3 Polyunsaturated Fatty Acid Supplementation Improves Neurologic Recovery and Attenuates White Matter Injury after Experimental Traumatic Brain Injury

Abstract

Dietary supplementation with omega-3 (o-3) fatty acids is a safe, economical mean of preventive medicine that has shown protection against several neurologic disorders. The present study tested the hypothesis that this method is protective against controlled cortical impact (CCI). Indeed, mice fed with o-3 polyunsaturated fatty acid (PUFA)-enriched diet for 2 months exhibited attenuated short and long-term behavioral deficits due to CCI. Although o-3 PUFAs did not decrease cortical lesion volume, these fatty acids did protect against hippocampal neuronal loss after CCI and reduced pro-inflammatory response. Interestingly, o-3 PUFAs prevented the loss of myelin basic protein (MPB), preserved the integrity of the myelin sheath, and maintained the nerve fiber conductivity in the CCI model. o-3 PUFAs also directly protected oligodendrocyte cultures from excitotoxicity and blunted the microglial activation-induced death of oligodendrocytes in microglia/oligodendrocyte cocultures. In sum, o-3 PUFAs elicit multifaceted protection against behavioral dysfunction, hippocampal neuronal loss, inflammation, and loss of myelination and impulse conductivity. The present report is the first demonstration that o-3 PUFAs protect against white matter injury in vivo and in vitro. The protective impact of o-3 PUFAs supports the clinical use of this dietary supplement as a prophylaxis against traumatic brain injury and other nervous system disorders.

Omega-3 polyunsaturated fatty acid supplementation and white matter changes in major depression

“…In addition, dietary supplementation with EPA and DHA prior to impact acceleration brain injury reduces the number of axons positive for beta amyloid precursor protein (APP), a marker of brain injury, at 30 days post-injury, to amounts comparable to those in uninjured rodents (84). Furthermore, a PUFA-enriched diet prevents post-injury loss of myelin, preserving the integrity of the myelin sheath, and maintaining the nerve fiber conductivity (85). In a different paradigm, maternal omega-3 fatty acid supplementation protects the neonatal rat brain from white matter injury due to lipopolysaccharide exposure (86).…”

N-3 polyunsaturated fatty acids in animal models with neuroinflammation: An update

“…Supplementing mice with a DHA-and EPAenriched diet (1.5% of total diet weight) 60 days prior to controlled cortical impact decreases IL-1, IL-1 and TNF- mRNA expression following the injury compared to mice fed a low n-3 PUFA control. Mice on a high n-3 PUFA diet also exhibit lower COX-2 mRNA and protein concentrations following controlled cortical impact (Pu et al, 2013). A separate study found that following controlled cortical impact, CD68 protein levels are lower in mice consuming 40 mg/kg of DHA compared to no supplementation (Mills et al, 2011).…”

Behavioral experiences as drivers of oligodendrocyte lineage dynamics and myelin plasticity

“…PUFAs are integral components of cell membranes including myelin membranes (Yurlova et al, 2011). Omega-3 fatty acids appear to play a protective role during demyelination, resulting in increased oligodendrocyte survival and preserved integrity of the myelin sheath (S. Lim et al, 2013;Pu et al, 2013;Salvati et al, 2013) During remyelination, omega-3 fatty acid administration was found to result in increased CNPase expression (a marker of oligodendrocyte differentiation) and increased levels of myelin gene mRNAs (Salvati et al, 2008).…”