L-Ornithine-L-aspartate (LOLA), a crystalline salt, is used primarily in the management of hepatic encephalopathy. The degree to which it might penetrate the brain, and the effects it might have on metabolism in brain are poorly understood. Here, to investigate the effects of LOLA on brain energy metabolism we incubated brain cortical tissue slices from guinea pig (Cavea porcellus) with the constituent amino acids of LOLA, L-ornithine or L-aspartate, as well as LOLA, in the presence of [1-13C]D-glucose and [1,2-13C]acetate; these labelled substrates are useful indicators of brain metabolic activity. L-Ornithine produced significant "sedative" effects on brain slice metabolism, most likely via conversion of ornithine to GABA via the ornithine aminotransferase pathway, while L-aspartate showed concentration-dependent excitatory effects. The metabolic effects of LOLA reflected a mix of these two different processes and were concentration-dependent. We also investigated the effect of an intraperitoneal bolus injection of L-ornithine, L-aspartate or LOLA on levels of metabolites in kidney, liver and brain cortex and brain stem in mice (C57Bl6J) 1 h later. No significant changes in metabolite levels were seen following the bolus injection of L-aspartate, most likely due to rapid metabolism of aspartate before reaching the target tissue. Brain cortex glutamate was decreased by L-ornithine but no other brain effects were observed with any other compound. Kidney levels of aspartate were increased after injection of L-ornithine and LOLA which may be due to interference by ornithine with the kidney urea cycle. It is likely that without optimising chronic intravenous infusion, LOLA has minimal impact on healthy brain energy metabolism due to systemic clearance and the blood - brain barrier.

中文翻译：

---

L-天冬氨酸，L-鸟氨酸和L-鸟氨酸-L-天冬氨酸（LOLA）及其对脑能量代谢的影响。

L-鸟氨酸-L-天冬氨酸（LOLA）是一种结晶盐，主要用于治疗肝性脑病。人们对它可能渗透到大脑的程度以及对大脑代谢的影响知之甚少。在这里，为了研究LOLA对脑能量代谢的影响，我们在有以下药物存在的情况下，将豚鼠（Cavea porcellus）的大脑皮层组织切片与LOLA，L-鸟氨酸或L-天冬氨酸的组成氨基酸以及LOLA一起孵育[1-13C] D-葡萄糖和[1,2-13C]乙酸盐；这些标记的底物是大脑代谢活动的有用指标。L-鸟氨酸对脑片代谢产生明显的“镇静”作用，最有可能是通过鸟氨酸氨基转移酶途径将鸟氨酸转化为GABA引起的，而L-天冬氨酸则表现出浓度依赖性的兴奋作用。LOLA的代谢作用反映了这两种不同过程的混合，并且是浓度依赖性的。我们还研究了腹膜内推注L-鸟氨酸，L-天冬氨酸或LOLA对1小时后小鼠（C57B16J）肾脏，肝和大脑皮层以及脑干中代谢产物水平的影响。推注L-天冬氨酸后未观察到代谢物水平的显着变化，这很可能是由于天冬氨酸在到达靶组织之前快速代谢所致。L-鸟氨酸可降低大脑皮层谷氨酸的含量，但使用其他任何化合物均未观察到其他大脑影响。注射L-鸟氨酸和LOLA后，肾脏中天冬氨酸水平升高，这可能是由于鸟氨酸干扰了肾脏尿素循环。如果没有优化长期静脉输液，