Abstract
Previous studies suggest that long‐term supplementation and dietary intake of omega‐3 polyunsaturated fatty acids (PUFAs) may have neuroprotective effects following brain injury. The objective of this study was to investigate potential neuroprotective effects of omega‐3 PUFAs on white matter following closed‐head trauma. The closed‐head injury model of engineered rotational acceleration (CHIMERA) produces a reproducible injury in the optic tract and brachium of the superior colliculus in mice. Damage is detectable using diffusion tensor imaging (DTI) metrics, particularly fractional anisotropy (FA), with sensitivity comparable to histology. We acquired in vivo (n = 38) and ex vivo (n = 41) DTI data in mice divided into sham and CHIMERA groups with two dietary groups: one deficient in omega‐3 PUFAs and one adequate in omega‐3 PUFAs. We examined injury effects (reduction in FA) and neuroprotection (FA reduction modulated by diet) in the optic tract and brachium. We verified that diet did not affect FA in sham animals. In injured animals, we found significantly reduced FA in the optic tract and brachium (~10% reduction, p < 0.001), and Bayes factor analysis showed strong evidence to reject the null hypothesis. However, Bayes factor analysis showed substantial evidence to accept the null hypothesis of no diet‐related FA differences in injured animals in the in vivo and ex vivo samples. Our results indicate no neuroprotective effect from adequate dietary omega‐3 PUFA intake on white matter damage following traumatic brain injury. Since damage from CHIMERA mainly affects white matter, our results do not necessarily contradict previous findings showing omega‐3 PUFA‐mediated neuroprotection in gray matter.
Highlights
Polyunsaturated fatty acids (PUFA)s are important in the brain's inflammatory response (Bazinet & Layé, 2014; Layé, 2010; Layé, Nadjar, Joffre, & Bazinet, 2017; Trépanier, Hopperton, Orr, & Bazinet, 2016)
We focused on the injured animals to examine the potential neuroprotective effect of omega-3 PUFAs
We replicated the effects of closed-head injury model of engineered rotational acceleration (CHIMERA) that had been previously observed with histology ex vivo diffusion tensor imaging (DTI) and histology with both sets of data
Summary
Polyunsaturated fatty acids (PUFA)s are important in the brain's inflammatory response (Bazinet & Layé, 2014; Layé, 2010; Layé, Nadjar, Joffre, & Bazinet, 2017; Trépanier, Hopperton, Orr, & Bazinet, 2016). The relative concentration of omega-6 and omega-3 PUFAs is important for inflammation since once they are released from the membrane, omega-6 PUFAs have pro-inflammatory effects, while omega-3 PUFAs have anti-inflammatory effects (Bazán, 1970; Rehncrona, Westerberg, Åkesson, & Siesjö, 1982; Yoshida et al, 1986). Long-term omega-3 PUFA supplementation reduces omega-6 PUFA metabolites released from damaged tissue and offers anti-inflammatory effects (Cao et al, 2006, 2007). These effects include decreased pro-inflammatory microglial cell density and cytokine activity in damaged tissue. In ischemia and traumatic brain injury (TBI), these anti-inflammatory effects reduce neuronal damage and cell death that preserve gray matter and improve cognitive and behavioral outcomes (Cao et al, 2007; Desai et al, 2016; Desai, Kevala, & Kim, 2014; Fernandes, Mori, Ekuni, Oliveira, & Milani, 2008; Lalancette-Hébert et al, 2011; Okada et al, 1996; Pan et al, 2009; Zhang et al, 2014; Zhang, Hu, Yang, Gao, & Chen, 2010)
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