Elucidation of Inflammation Processes Exacerbating Neuronal Cell Damage to the Retina and Brain Visual Centers as Quest for Therapeutic Drug Targets in Rat Model of Blast Overpressure Wave Exposure
Abstract
A frequent cause of traumatic eye injuries to soldiers is exposure to blast shock waves; and it can involve cellular damage to the retina as well as brain visual centers. Since there are relatively few animal studies that have studied this, there is an urgent need to advance the characterization of blast induced visual system injuries and identify potential drug therapies. Inflammation plays a key role in the destruction of injured neuronal tissues, as carried out by immune cells; and thus is a promising target. Scope and timing, however, of this process must be better understood. Our study uses an adult rat model of eye and brain injuries, as produced by exposure to simulated blast waves in a shock tube. Rats are kept on an omega-3 polyunsaturated fatty acid deficient diet, which promotes inflammation. Conversely, some are fed an omega-3 enriched diet by ocean fish oil supplementation. Up to one month after blast, eye (retina) and brain damage is assessed by electroretinography (ERG), visual acuity task, magnetic resonance imaging (MRI), histopathology, and immunoassay arrays for inflammation signaling factors. Our findings reveal that blast wave exposure leads to acute (i.e., within 3 days) impairment of visual function with underlying infiltration of activated immune cells (i.e., macrophages and microglia) in the brain and retina, which is accompanied by elevated cytokines and degeneration of neurons. Despite having potent anti-inflammatory properties, high doses of dietaryomega-3 fatty acids showed slight if any ability to alleviate these acute injury events. Chronic events, however, maybe more amendable to other functions of omega-3 fatty acids, such as the rebuilding of neuronal cell membranes. Thus, we plan to extend our evaluations over more prolonged post-blast time periods. Overall, our mission is to provide results that will lead to selection and animal testing of new drugs for blast-induced damage sustained to the visual system of US Army personnel.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2016
- Accession Number
- AD1032094
Entities
People
- James C. Demar