Evaluation of Novel Polyunsaturated Fatty Acid Derived Lipid Mediators of Inflammation to Ameliorate the Deleterious Effects of Blast Overpressure on Eye and Brain Visual Processing Centers in Rats.

摘要

In an adult rat model of blast wave exposure, we examined the efficacy of four drugs known to be polyunsaturated fatty acid derived lipid mediators of inflammation, i.e., lipoxin A4 (LXA4), protectin DX (PDX), resolvin D1 (RVD1), and resolvin E1 (RVE1), to alleviate neuronal cell damage to the eyes (retinas) and brain visual centers. Rats were placed in a compressed air driven shock tube and exposed, right side on, once to a 20 psi (260 Hz) blast over pressure wave. The drugs were immediately administered to the blasted rats by intravenous injection (25 g/kg), and then given every other day out to 14 days. Injury outcome measures were electroretinography (ERG), visual discrimination behavioral testing, and histopathology (n = 8, 9, 9, and 9, respectively). Blasted rats were assessed at baseline and then out to 14 days post-exposure. ERG based light signaling responses of their eyes showed a drug efficacy order of RVE1 > LXA4 > PDX > RVD1. Visual discrimination testing of their ability to press a lever with a cue light, yielded a drug efficacy order of RVD1 > RVE1 > PDX LXA4. Histopathology of their retinas and associated brain optic tracts for neuronal cell degeneration gave a drug efficacy order of RVD1 > LXA4 > PDX RVE1 and LXA4 > RVD1 > RVE1 PDX, respectively. For all outcome measures, these drugs at best produced modest injury improvements for the blasted retina and brain, suggesting they have a rather limited potential as visual system therapeutics.