Cerebrolysin Use in Patients with Liver Damage—A Translational Study

SIMPLE SUMMARY: Given the prevalence of non-alcoholic fatty liver disease (NAFLD), there is a high chance that some of these patients can develop acute life-threatening events such as stroke. Our aim was to understand if the use of Cerebrolysin could be an option for stroke patients with altered liver enzymes levels. We also wanted to evaluate whether the treatment could reverse the inhibition of hippocampal neurogenesis in mice receiving methionine/clonidine deficiency (MCD) food. Cerebrolysin proved safe for clinical use in stroke patients with liver damage, although it could not reverse the inhibition of hippocampal neurogenesis to mice fed MCD. ABSTRACT: The treatment of acute life-threatening events in patients suffering from chronic pathologies is problematic, as physicians need to consider multisystemic drug effects. Regarding Cerebrolysin, a Sonic Hedgehog signaling pathway amplifier and one of the few approved neurotrophic treatments for stroke patients, concerns of excessive Hedgehog pathway activation that could accelerate NAFLD progression to cirrhosis seem valid. We investigated stroke patients treated with Cerebrolysin that presented elevated levels of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT). We also investigated the efficiency of Cerebrolysin in reversing the neurogenesis inhibition within the hippocampus in a mouse model of NAFLD by evaluating behavior and histological outcomes. NeuN, BrdU and Iba1 positive signals in the cortex and hippocampus of the animals were also observed. Clinically, Cerebrolysin improved AST levels in a majority of stroke patients with hepatic damage. The same treatment in an experimental setup was able to reverse anxiety-like behavior in MCD mice, reducing their freezing time from 333.61 ± 21.81 s in MCD animals to 229.17 ± 26.28 in treated ones. The use of Cerebrolysin did not improve short-term memory nor rescued cell multiplication in the hippocampus after MCD food intake. Understanding the neuroprotective and neurotrophic effects that drugs have on NAFLD patients can significantly contribute to a suitable therapeutic approach.