Dietary Docosahexaenoic Acid Improves Cognitive Function, Tissue Sparing, and Magnetic Resonance Imaging Indices of Edema and White Matter Injury in the Immature Rat after Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children. Specific therapies to treat acute TBI are lacking. Cognitive impairment from TBI may be blunted by decreasing inflammation and oxidative damage after injury. Docosahexaenoic acid (DHA) decreases cognitive impairment, oxidative stress, and white matter injury in adult rats after TBI. Effects of DHA on cognitive outcome, oxidative stress, and white matter injury in the developing rat after experimental TBI are unknown. We hypothesized that DHA would decrease early inflammatory markers and oxidative stress, and improve cognitive, imaging and histologic outcomes in rat pups after controlled cortical impact (CCI). CCI or sham surgery was delivered to 17 d old male rat pups exposed to DHA or standard diet for the duration of the experiments. DHA was introduced into the dam diet the day before CCI to allow timely DHA delivery to the preweanling pups. Inflammatory cytokines and nitrates/nitrites were measured in the injured brains at post-injury Day (PID) 1 and PID2. Morris water maze (MWM) testing was performed at PID41-PID47. T2-weighted and diffusion tensor imaging studies were obtained at PID12 and PID28. Tissue sparing was calculated histologically at PID3 and PID50. DHA did not adversely affect rat survival or weight gain. DHA acutely decreased oxidative stress and increased anti-inflammatory interleukin 10 in CCI brains. DHA improved MWM performance and lesion volume late after injury. At PID12, DHA decreased T2-imaging measures of cerebral edema and decreased radial diffusivity, an index of white matter injury. DHA improved short-and long-term neurologic outcomes after CCI in the rat pup. Given its favorable safety profile, DHA is a promising candidate therapy for pediatric TBI. Further studies are needed to explore neuroprotective mechanisms of DHA after developmental TBI.

Imaging and serum biomarkers reflecting the functional efficacy of extended erythropoietin treatment in rats following infantile traumatic brain injury

“…45 Though a mouse model of frontal lobe CCI injury to a toddler-age equivalent (P21) has shown a chronic motor deficit, 17 no other preclinical models of infant or toddler TBI have shown chronic motor deficits following early CCI. 1,84,106 Thus, even though the deficits detected in the present study were subtle, this is the first time that chronic significant gait differences in infant CCI-veh rats were identified. Most importantly, EPO treatment reversed the motor deficits.…”

“…In a preclinical model of toddler TBI with P17 CCI, a reduction in white matter RD related to an oral treatment regimen was observed. 84 Indeed, detailed imaging studies have demonstrated differences in treatment groups when preterm infants were imaged at a term-equivalent age, 5,46 a relatively short interval of a few months to detect structural improvement in neurodevelopment in humans. These recent reports, 5,46 in combination with data presented here, suggest that DTI may be used as an imaging biomarker in infant TBI to measure responsiveness to neuro-reparative strategies.…”

Deficits in Docosahexaenoic Acid Accrual during Adolescence Reduce Rat Forebrain White Matter Microstructural Integrity: An in vivo Diffusion Tensor Imaging Study

“…An ex vivo study found that RD was elevated in demyelinating spinal cord tissue from multiple sclerosis patients [55]. It is also notable that DHA blunted elevated RD in the neonatal rat brain following controlled cortical impact [56]. However, an ex vivo study found that RD was significantly correlated with MBP immunolabeling only in commissural WM tracts [57].…”

Diffusion Imaging of White Matter in Schizophrenia: Progress and Future Directions

“…This technique is intriguing, as it would allow us to further understand the impact of immune factors on brain structure. Moreover, there is evidence that omega-3 fatty acids have anti-inflammatory effects (140, 141). Thus, in addition to the previously discussed role for PUFA supplementation in supporting myelination, it is also possible that the preventative effects are related to inflammation.…”