Antioxidants prevent inflammation and preserve the optic projection and visual function in experimental neurotrauma.

Bernardo-Colón A, Vest V, Clark A, Cooper ML, Calkins DJ, Harrison FE, Rex TS
Cell Death Dis. 2018 9 (11): 1097

PMID: 30367086 · PMCID: PMC6203845 · DOI:10.1038/s41419-018-1061-4

We investigated the role of oxidative stress and the inflammasome in trauma-induced axon degeneration and vision loss using a mouse model. The left eyes of male mice were exposed to over-pressure air waves. Wild-type C57Bl/6 mice were fed normal, high-vitamin-E (VitE), ketogenic or ketogenic-control diets. Mice lacking the ability to produce vitamin C (VitC) were maintained on a low-VitC diet. Visual evoked potentials (VEPs) and retinal superoxide levels were measured in vivo. Tissue was collected for biochemical and histological analysis. Injury increased retinal superoxide, decreased SOD2, and increased cleaved caspase-1, IL-1α, IL-1β, and IL-18 levels. Low-VitC exacerbated the changes and the high-VitE diet mitigated them, suggesting that oxidative stress led to the increase in IL-1α and activation of the inflammasome. The injury caused loss of nearly 50% of optic nerve axons at 2 weeks and astrocyte hypertrophy in mice on normal diet, both of which were prevented by the high-VitE diet. The VEP amplitude was decreased after injury in both control-diet and low-VitC mice, but not in the high-VitE-diet mice. The ketogenic diet also prevented the increase in superoxide levels and IL-1α, but had no effect on IL-1β. Despite this, the ketogenic diet preserved optic nerve axons, prevented astrocyte hypertrophy, and preserved the VEP amplitude. These data suggest that oxidative stress induces priming and activation of the inflammasome pathway after neurotrauma of the visual system. Further, blocking the activation of the inflammasome pathway may be an effective post-injury intervention.

MeSH Terms (20)

Animals Antioxidants Ascorbic Acid Axons Diet, Ketogenic Disease Models, Animal Evoked Potentials, Visual Inflammasomes Inflammation Interleukin-1alpha Interleukin-1beta Male Mice Mice, Inbred C57BL Optic Nerve Injuries Oxidative Stress Reactive Oxygen Species Retina Superoxides Vitamin E

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