Table 2.

Outline of studies in which ω-3 fatty acids or ω-3 fatty acids plus curcumin were provided prior to injury, mild traumatic brain injury, or traumatic brain injury

Study	Animal injury model	Supplementation dosing	Pathophysiological outcomes	Functional outcomes
Wu et al. [133]	Sprague–Dawley rats Mild fluid percussion injury	RD (0.9% DHA/1.0% EPA) FO (12.4% DHA/13.5% EPA) 4 wk prior to injury	FO-fed rats had less post-TBI oxidative damage than RD-fed rats FO-fed rats exhibited normalized post-TBI levels of hippocampal BDNF, synapsin I, and CREB compared with RD-fed rats	FO-fed rats performed better in post-TBI Morris water maze testing compared with RD-fed rats
Wu et al. [131]	Sprague–Dawley rats Mild fluid percussion injury	RD (0.9% DHA/1.0% EPA) FO (12.4% DHA/13.5% EPA) 4 weeks prior to injury	FO-fed rats had less post-TBI oxidative damage compared with RD-fed rats FO-fed rats exhibited normalized post-TBI levels of hippocampal Sir2α, AMPK, p-AMPK, and uMtCK compared with RD-fed rats
Mills et al. [126]	Sprague–Dawley rats Marmarou impact acceleration injury	DHA only 0 mg kg− day−1 4 mg kg−1 day−1 12 mg kg−1 day−1 40 mg kg−1 day−1 30 days prior to injury	40 mg kg−1 day−1 DHA-fed rats with 4.7 × the amount of serum DHA than lower doses 40 mg kg−1 day−1 DHA-fed rats with significantly fewer APP-positive axons than lower doses 40 mg kg−1 day−1 DHA-fed rats with significantly fewer caspase-3 positive axons than lower doses 40 mg kg−1 day−1 DHA-fed rats with significantly fewer CD-68 positive macrophages than lower doses	40 mg kg−1 day−1 DHA-fed rats performed better in post-TBI Morris water maze testing compared with lower doses
Pu et al. [127]	Male C57BL/6J mice Controlled cortical impact	RD (0.5% omega-3 fatty acids) FO (15 g kg−1 day−1 omega-3 fatty acids) 60 days prior injury	No significant difference in volume of cortical lesions No significant difference in the number of viable neurons within CA1 region of hippocampus FO-fed mice had significantly more viable neurons within CA3 region of hippocampus post-TBI compared with RD-fed mice FO-fed mice with significantly fewer post-TBI activated microglia and significantly less mRNA levels of IL-1β, TNFα, COX-II, and iNOS compared with RD-fed mice	FO-fed mice had fewer sensorimotor deficits compared with RD-fed mice FO-fed mice performed better in post-TBI Morris water maze testing compared with RD-fed rats
Wang et al. [128]	Sprague–Dawley rats Repetitive (2) mild fluid percussion injury	RD (0% fish oil) FO (0.6% DHA/0.8–1.0% EPA) 4 wk prior to injury	No significant difference in hippocampal neuron density between groups	FO-fed rats performed better in post-TBI Morris water maze testing compared with RD-fed rats
Wu et al. [73]	Sprague–Dawley rats Mild fluid percussion injury	RD Curcumin diet 500 ppm curcumin DHA diet (1.2% DHA) DHA + curcumin diet (500 ppm curcumin + 1.2% DHA)	Curcumin diet, DHA diet, and DHA + curcumin diet-fed rats normalized post-TBI levels of hippocampal BDNF and p-TrkB compared with RD-fed rats Curcumin diet, DHA diet, and DHA + curcumin diet-fed rats significantly reduced post-TBI lipid peroxidation compared with RD-fed rats Curcumin diet, DHA diet, and DHA + curcumin diet-fed rats normalized post-TBI levels of FADS2 and 17β-HSD4 compared with RD-fed rats Curcumin diet, DHA diet, and DHA + curcumin diet-fed rats exhibited preserved brain DHA content post-TBI compared with RD-fed rats	Curcumin diet, DHA diet, and DHA + curcumin diet-fed rats performed better in post-TBI Barnes maze testing compared with RD-fed rats

AMPK AMP-activated protein kinase, APP-positive amyloid precursor protein, BDNF brain-derived neurotrophic factor, COX-II cytochrome c oxidase II, CREB cAMP response element-binding protein, DHA docosahexaenoic acid, EPA eicosapentaenoic acid, FADS2 Δ6 fatty acid desaturase, FO fish-oil diet, IL-1β interleukin-1β, iNOS inducible nitric oxide, p-AMPK phosphorylated AMP-activated protein kinase, ppm parts-per million, p-TrkB phospho-tropomyosin receptor kinase B, RD regular diet, Sir2α silent information regulator 2α, TBI traumatic brain injury, TNFα tumor necrosis factor alpha, uMtCK ubiquitous mitochondrial creatine kinase, 17β-HSD4 17β-hydroxysteroid dehydrogenase type 4