Neuroprotective Effect of the Ketone Bodies Acetoacetate and β-hydroxybutyrate on Retinal Ganglion Cells in a Rat Model of NMDA Toxicity

Abstract

Purpose: : Ketone bodies (acetoacetate and beta-hydroxybutyrate) produced endogenously during starvation have been shown to exhibit neuroprotective and antiepileptic properties in models of brain ischemia and experimental epilepsy. Aim of this study was to investigate neuroprotective properties of systemic applicated lithium acetoacetate or sodium beta-hydroxybutyrate after N-methyl-D-aspartate (NMDA) damage of rat retinal ganglion cells.Material and

Methods: : Brown-Norway rats were used for the study. Lithium acetoacetate in two doses (250 mg/kg body weight (bw) and 62.5mg/kg bw [¼ dose]) and sodium beta-hydroxybutyrate in molar equivalent of the lithium acetoacetate doses (291.2 mg/kg bw and 72.8 mg/kg bw [¼ dose]) or phosphate buffer saline as control were administered intraperitoneally once a day for 21 consecutive days. On day 14 animals received intraocular NMDA (2 µl of 10mmol/l solution in PBS). On day 19 retinal ganglion cells were labeled retrogradely with Fluorogold. 2 days later rats were sacrificed, retinas were flatmounted and numbers of retinal ganglion (cells per mm²) were counted and compared to controls.

Results: : Retinal ganglion cell numbers in retinas from animals treated with lithium acetoacetate or sodium beta-hydroxybutyrate in full doses were significantly higher (48.4% and 41.5% increases, respectively; P<0.001, ANOVA) than in those treated with PBS. However, ¼ doses of both substances turned out to be ineffective.

Keywords: neuroprotection • cell survival • excitatory amino acid receptors