Cerebrolysin Use in Patients with Liver Damage-A Translational Study.

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.

Cerebrolysin Prevents Brain Injury in a Mouse Model of Liver Damage.

Liver damage can lead to secondary organ damage by toxic substances and catabolic products accumulation which can increase the permeability of blood-brain barrier, leading to cognitive impairment. The only real treatment for end stage liver failure is grafting. With some, but not all, neurological symptoms subsiding after transplantation, the presence of brain damage can impair both the short and long-term outcome. We tested if Cerebrolysin can prevent brain injury in an experimental model of non-viral liver damage in mice. Behavior, abdominal ultrasound evaluation and immunohistochemistry were used to evaluate the animals. No ultrasound or behavior differences were found between the control and treated animals, with both groups displaying more anxiety and no short-term memory benefit compared to sham mice. Cerebrolysin treatment was able to maintain a normal level of cortical NeuN+ cells and induced an increase in the area occupied by BrdU+ cells. Surprisingly, no difference was observed when investigating Iba1+ cells. With neurological complications of end-stage liver disease impacting the rehabilitation of patients receiving liver grafts, a neuroprotective treatment of patients on the waiting lists might improve their rehabilitation outcome by ensuring a minimal cerebral damage.