Dietary blueberry before and/or after exposure to HZE particle radiation attenuates neuroinflammation, oxidative stress, glial cell activation, and memory deficits in rats

Background: Acute neuroinflammatory and oxidative-stress (OS)-inducing stressors, such as high energy and charge (HZE) particle irradiation, produce accelerated aging in the brain. Anti-inflammatory and antioxidant foods, such as blueberries (BB), attenuate neuronal and cognitive deficits when administered to rodents before or both before and after HZE particle exposure. However, the effects of post-stressor treatments are unknown and may be important to repair initial damage and prevent progressive neurodegeneration.

Objective: This study assessed the differential efficacy and mechanistic targets of a BB-supplemented diet before and/or after HZE particle irradiation on neuroinflammation, OS, glial cell activation, and memory deficits.

Methods: Two-month-old male Sprague-Dawley rats (n=120) consumed a 2% BB or control diet for 45 days. Rats were whole-body irradiated (150 cGy ⁵⁶Fe) or were not irradiated, followed by a 45-day post-treatment interval in which they were fed a 2% BB or control diet. The novel object recognition test (NOR) was performed at the end of the post-treatment interval to evaluate memory. Biomarkers of neuroinflammation, OS, and glial cell activity were evaluated in the hippocampus and frontal cortex of rat brains following euthanasia. Statistical analyses included analysis of variance, t-tests, and Pearson correlations.

Results: Pre- and/or post-irradiation BB treatments were similarly effective at reducing ⁵⁶Fe-induced recognition memory deficits on the NOR and the protein and/or mRNA expression of neuroinflammatory factors (tumor necrosis factor-ɑ [TNFɑ], inducible nitric oxide synthase [iNOS], cyclooxygenase-2 [COX-2], phosphorylated IκB-α [pIκB-ɑ]), one mediator of oxidative stress (NADPH oxidase [NOX2]), and markers for microglia and astrocyte activity (CD68 and glial fibrillary acidic protein [GFAP]) in the frontal cortex and hippocampus of rats 45 days post-irradiation (p < 0.05).

Conclusions: Findings support the use of dietary post-treatments with antioxidant and anti-inflammatory properties to attenuate biochemical changes in the brain and memory deficits following acute neuroinflammatory/OS-inducing stressors, in addition to having protective benefits.