Repetitive and Prolonged Omega-3 Fatty Acid Treatment after Traumatic Brain Injury Enhances Long-Term Tissue Restoration and Cognitive Recovery

Abstract

Traumatic brain injury (TBI) is one of the most disabling clinical conditions that could lead to neurocognitive disorders in survivors. Our group and others previously reported that prophylactic enrichment of dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) markedly ameliorate cognitive deficits after TBI. However, it remains unclear whether a clinically relevant therapeutic regimen with n-3 PUFAs administered after TBI would still offer significant improvement of long-term cognitive recovery. In the present study, we employed the decline of spatial cognitive function as a main outcome after TBI to investigate the therapeutic efficacy of post-TBI n-3 PUFA treatment and the underlying mechanisms. Mice were subjected to sham operation or controlled cortical impact, followed by random assignment to receive the following four treatments: (1) vehicle control; (2) daily intraperitoneal injections of n-3 PUFAs for 2 weeks, beginning 2 h after TBI; (3) fish oil dietary supplementation throughout the study, beginning 1 day after TBI; or (4) combination of treatments (2) and (3). Spatial cognitive deficits and chronic brain tissue loss, as well as endogenous brain repair processes such as neurogenesis, angiogenesis, and oligodendrogenesis, were evaluated up to 35 days after TBI. The results revealed prominent spatial cognitive deficits and massive tissue loss caused by TBI. Among all mice receiving post-TBI n-3 PUFA treatments, the combined treatment of fish oil dietary supplement and n-3 PUFA injections demonstrated a reproducible beneficial effect in attenuating cognitive deficits although without reducing gross tissue loss. Mechanistically, the combined treatment promoted post-TBI restorative processes in the brain, including generation of immature neurons, microvessels, and oligodendrocytes, each of which was significantly correlated with the improved cognitive recovery. These results indicated that repetitive and prolonged n-3 PUFA treatments after TBI are capable of enhancing brain remodeling and could be developed as a potential therapy to treat TBI victims in the clinic.

Acrylamide-induced adverse cerebellar changes in rats: possible oligodendrogenic effect of omega 3 and green tea

“…Confirming these findings, the area per cent of PDGF positive reaction in this work was significantly increased in Group III as compared to all groups. Supporting our results, the combined treatment of fish oil dietary supplement and omega 3 polyunsaturated fatty acids injections had been proved to promote post-TBI restorative processes in the brain, including generation of immature neurons, microvessels, and oligodendrocytes, each of which was significantly correlated with the improved cognitive recovery [30]. Oligodendrocytes were abundant in H&E sections of omega 3 plus-treated rats in this work.…”

“…In addition to the treatment of hypertriglyceridaemia, a preparation of omega 3-acid ethyl esters is licensed in the United Kingdom for the prevention of recurrent events after MI [32]. Recently, the combined treatment of fish oil dietary supplement and omega 3 polyunsaturated fatty acids injections had been proved to promote post-traumatic brain injury (TBI) restorative processes in the brain, including generation of immature neurons, microvessels, and oligodendrocytes, each of which was significantly correlated with the improved cognitive recovery [30].…”

Investigation of the effect of dietary intake of omega‐3 polyunsaturated fatty acids on trauma‐induced white matter injury with quantitative diffusion MRI in mice

“…In mice, CHIMERA reliably produces axonal damage and induces inflammatory effects in the optic tract and brachium of the superior colliculus (Haber et al, 2017;Namjoshi et al, 2014). This pattern of damage differs from the types investigated in the previous studies, which included a focal lesion (Pu et al, 2013(Pu et al, , 2017, and strong damage to the corticospinal tract and medial lemniscus Mills et al, 2010Mills et al, , 2011.…”

Dual roles of astrocytes in plasticity and reconstruction after traumatic brain injury

“…Astrocytes, a type of glial cells, are involved in the homeostasis and blood flow control of the central nervous system (CNS) [12]. TBI is known to induce astrocyte activation (reactive astrogliosis), which is involved in tissue remodeling processes such as neurogenesis, synaptogenesis, repair of the blood-brain barrier (BBB), regulation of synaptic plasticity, and formation of glial scar and extracellular matrix (ECM), weighing a lot to the patient outcome [13][14][15]. However, reports on the effects of reactive astrogliosis are not consistent [10,[16][17][18].…”