Cerebrolysin

Abstract

Schizophrenia is known as a complex and devastating mental disorder due to its profound impact on individuals, families, and society. Emerging evidence proposes that mitochondria play a central role in schizophrenia. Here, we investigated whether cerebrolysin (CBL) can alleviate anxiety-like behaviors and cognitive deficits through a mechanism involving the CREB/PGC-1α pathway. In this study, 30 male BALB/c mice were randomly assigned to three different groups: Control, Ketamine, and Ketamine + CBL. Intraperitoneal injection of ketamine was performed at 20 mg/kg for 14 consecutive days. CBL was delivered intraperitoneally at 2.5 mL/kg once daily for seven days, starting from the 8th day to the 14th day of the experiment. The novel object recognition and elevated plus-maze tests were used to assess episodic-like memory and anxiety, respectively. Hippocampal tissue was examined not only for alterations in mitochondrial activity, encompassing ATP production and levels of reactive oxygen species (ROS), but also for estimating CREB, p-CREB, and PGC-1α protein levels. Behavioral results indicated that treatment with CBL reversed anxiety-like behavior and cognitive dysfunction caused by ketamine. Additionally, ketamine increased the production of ROS and reduced ATP levels in the hippocampus, while CBL treatment restored these changes. Furthermore, CBL therapy upregulated the hippocampal expression of the proteins CREB, p-CREB, and PGC-1α compared with the ketamine-treated animals. It is speculated that treatment with CBL can attenuate ketamine-induced cognitive deficits and anxiety-like behaviors through the upregulation of the CREB/PGC-1α pathway and the improvement of mitochondrial function.

Abstract

Background/Objectives: Cerebrolysin is a well-known mixture of peptides that has been used for many years, primarily in patients with neurological disorders. Thanks to its unique properties, this substance supports endogenous repair mechanisms and protects the brain from damaging factors. Cerebrolysin is most widely used in Eastern European countries. However, data on the potential use of cerebrolysin in mental disorders are difficult to find in the literature. This review focuses on the potential use of cerebrolysin in psychiatry, and two independent researchers searched three full-text medical article databases to compile it. Methods: To conduct this scoping review, two independent researchers searched three full-text article databases, Embase, Scopus, and Web of Science, by entering the following phrases: "cerebrolysin psychiatry", "cerebrolysin depression", "cerebrolysin mood", "cerebrolysin bipolar", "cerebrolysin schizophrenia", and "cerebrolysin addiction". Results: The results show that this specific substance could have a relatively small application in psychiatry. Conclusions: The limited amount of available research on the use of cerebrolysin suggests that it may have some significance in supporting the treatment of depression and autism spectrum disorders and alleviating adverse effects during treatment with neuroleptics.

Abstract

Cerebrolysin (CBL), a peptide derived from pig brain, is recognized for its neuroprotective and anti-inflammatory properties. This research aimed to investigate the effects of CBL on anxiety- and depression-like behaviors, spatial memory, the tryptophan/kynurenine (TRP/KYN) pathway, and inflammation in the prefrontal cortex (PFC) of a mouse model for schizophrenia.

Abstract

Acute brain injury includes different pathologies: stroke, traumatic injury, subarachnoidale haemorhhage. In the pathophysiology of acute brain injury, secondary injury with hyperactivation of glia plays a crucial role. Activated glial cells induce prolonged inflammation that impacts the recovery and further cognitive functions of patients. In our study, we have examined the neuroprotective impact of exogenous neuropeptides-Cerebrolysin on astrocytes under different conditions. In a model that simulates central nervous system damage associated with brain injury, stroke, and subarachnoid hemorrhage, the U87MG human brain cancer (glioblastoma astrocytoma like) cells were treated with Cerebrolysin and exposed to conditions of continuous and cyclic hypoxia and red blood cell lysate overload. The activity and expression of cyclooxygenases COX-1 and COX-2 and on cytokines (IL-8, IL-1β, IL-6, IL-10) and chemokines (CCL5/RANTES, CXCL9/MIG, CCL2/MCP-1, and CXCL10/IP-10) concentration were assessed. Cerebrolysin lowers IL-1β and IL-6 and increases IL-10 under all conditions. Cerebrolysin may exhibit a neuroimmunotrophic function, reducing inflammation under conditions that replicate traumatic brain injury and hemorrhagic insults to the central nervous system. By modulating both pro-inflammatory and anti-inflammatory cytokines, Cerebrolysin can help create a more balanced immune response conducive to tissue repair and reduced secondary damage. Its ability to lower harmful mediators like IL-1β and IL-6 while enhancing protective factors such as IL-10 suggests a promising therapeutic strategy in stroke, traumatic brain injury, and subarachnoid hemorrhage. Alongside other mechanisms such as neurotrophic factor enhancement and glial cell regulation, this cytokine modulation underscores the therapeutic potential of Cerebrolysin in a variety of central nervous system disorders.

Abstract

Several psychopathologies may be triggered, among other factors, by stress or trauma in childhood. The maternal deprivation model (MD) replicates some of the core factors that may induce the onset of different psychopathologies like structural and plasticity defects. Among other brain regions, the amygdala is susceptible to stress and trauma and plays a key role in integrating social behavior. Several molecules, such as Cerebrolysin® (CBL), have been used to treat different symptoms by reversing the underlying neurobiological plasticity-related changes. In this study, maternal deprivation (MD) was conducted on 9-day-old male Sprague-Dawley rats (n = 28; 7 rats per group: Intact, Intact + CBL, MD, and MD + CBL). At 25 postnatal days (PND), CBL treatment was administered for 10 consecutive days, and social behavior was evaluated in a three-chamber social test at 35 PND. Moreover, Sholl analysis and immunohistochemistry were carried out for dendritic intersection and brain-derived neurotrophic factor (BDNF) presence in the amygdala, respectively. CBL treatment had an augmentative effect on intact animals in terms of social behavior and incidences, but no differences between MD and CBL-treated animals. Moreover, dendritic intersections and BDNF decreased after the MD protocol but increased by CBL treatment in MD animals. Our results show that CBL could be part of the treatment in case of a traumatic or stressful event in neurodevelopment, especially in the youth age. According to this preclinical study, CBL could help reverse symptoms of different psychopathologies caused by stress or trauma, with neurobiological changes underlying its effect.