▎Cerebrolysin Research
What is the research background of Cerebrolysin?
Early Research Foundation: In the early 20th century, scientists began to pay attention to the effects of some special substances in the brain on nerve cells. At that time, it was known that there were various bioactive substances in the brain, which played a key role in the growth, development, repair, and functional maintenance of nerve cells.
These early studies laid the theoretical foundation for the subsequent research and development of cerebrolysin, prompting researchers to attempt to extract and isolate bioactive components from brain tissues for the treatment of nervous system diseases.
Development of Extraction Technology: With the continuous progress of biochemistry and molecular biology technologies, researchers have more advanced means to extract and purify bioactive substances from brain tissues.
From the 1960s to the 1970s, some research teams successfully extracted complex mixtures from animal brain tissues such as pig brains, which contained a variety of amino acids, peptides, and other bioactive components. These extracts showed certain nutritional and protective effects on nerve cells in animal experiments and could promote the growth and repair of nerve cells.
Research on Composition and Mechanism of Action: After years of research, a deeper understanding of the composition and mechanism of action of cerebrolysin has been obtained. It has been found that cerebrolysin contains a variety of neurotransmitter precursors, neurotrophic factors, and other bioactive peptides. These components can cross the blood-brain barrier and enter the brain tissue, act on nerve cells, promote the metabolism of nerve cells, protein synthesis, and the release of neurotransmitters, thereby improving the function of nerve cells and playing a protective and reparative role for damaged nerve cells.
Exploration of Clinical Applications: Based on its good effects in animal experiments, cerebrolysin has gradually been applied to clinical research. Initially, it was mainly used to treat some neurodegenerative diseases of the nervous system, such as Alzheimer’s disease, Parkinson’s disease, and nerve function disorders caused by brain trauma, cerebrovascular diseases, etc. Clinical studies have shown that cerebrolysin can, to a certain extent, improve patients’ cognitive function, memory, language ability, and limb movement function, and improve patients’ quality of life.
What is the mechanism of action of Cerebrolysin?
1. It has a neuroprotective effect
Reducing Hypoxic Damage: In in vitro models, such as the PC12 cell model treated with cobalt chloride (CoCl2), Cerebrolysin exhibits a neuroprotective effect[1]. Specifically, it maintains the diameter of undifferentiated PC12 cells after CoCl2 treatment, reduces cell shrinkage; decreases the activity of pro-apoptotic Caspase in undifferentiated PC12 cells under CoCl2 stress; restores the metabolic activity of undifferentiated and differentiated PC12 cells damaged by CoCl2; and at the same time reduces the superoxide level observed after CoCl2 exposure. Its mechanism of action may be through increasing the phosphorylation of GSK3β, thereby inhibiting the activity of GSK3β. This may have clinical significance for Alzheimer’s disease, because the activity of GSK3β is related to the production of amyloid β.
Role in Ischemic Stroke: In patients with ischemic stroke, Cerebrolysin may play a neuroprotective role through multiple pathways. In early clinical trials, when studying the mildly affected stroke population, due to the generally good prognosis of this population, there may be floor or ceiling effects, resulting in no obvious differences between the treatment groups[2]. However, subgroup analysis of more severely affected patients showed that Cerebrolysin had a significant positive effect on enhancing recovery, and the magnitude of its effect increased with the severity of the stroke. In addition, Cerebrolysin can be safely combined with thrombolytic therapy. It not only has a neuroprotective effect but also has the potential for nerve recovery and shows efficacy in patients with moderate to severe stroke[2, 3].
2. As a nerve repair agent
Promoting Communication between Nerve Cells: Cerebrolysin is a protein-based liquid mixture containing 85% free amino acids and 15% bioactive low-molecular-weight amino acid sequences, including low-molecular-weight neuropeptides[4, 5]. These active brain neuropeptides can penetrate the blood-brain barrier and be used by neurons for communication with each other.
Effect on Neurodevelopmental Disorders: In child neuropsychiatry, Cerebrolysin is considered a peptidergic substance with a multimodal mechanism of action and acts as a nerve repair agent. In pervasive developmental disorders (PDD) including autism and Asperger’s syndrome, a new treatment method with injectable Cerebrolysin as the main treatment component showed that the autistic characteristics of all treated patients were improved and significantly reduced, and the main autistic characteristics of some patients completely disappeared without any side effects[5].
3. Therapeutic effect on post-stroke spasm
Improving Spasm-related Indicators: Through the study of a 56-year-old patient with chronic stroke, Cerebrolysin was injected intramuscularly into the spastic limb at a dose of 10 mL per day for 30 days. After treatment, spasm-related outcome indicators such as the Manual Muscle Test (MMT) improved by 70%, and the Modified Ashworth Scale (MAS) decreased by 2 points[6]. The patient also reported beneficial effects on mood and motivation.
4. Impact on liver injury
Improving Liver Injury Indicators: In patients with chronic diseases, the treatment of acute life-threatening events is complex. For stroke patients treated with Cerebrolysin, if there is an increase in aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT), clinical studies have shown that Cerebrolysin can improve the AST levels of most stroke patients with liver injury[7].
Reversing the Inhibition of Neurogenesis: In a mouse model of non-alcoholic fatty liver disease (NAFLD), by evaluating behavioral and histological outcomes, it was found that Cerebrolysin could reverse anxiety-like behavior but failed to improve short-term memory or rescue cell proliferation in the hippocampus after MCD food intake[7].
What are the applications of Cerebrolysin?
Applications in Pediatric Neuropsychiatry:
Promoting Nerve Cell Stimulation: In 1949, scientist Gerhart Harrer from the University of Innsbruck in Austria reported that Cerebrolysin, a protein liquid produced by the enzymatic hydrolysis of brain tissue, could stimulate nerve cells. Cerebrolysin is a protein-based liquid mixture composed of 85% free amino acids and 15% bioactive low-molecular-weight amino acid sequences, including low-molecular-weight neuropeptides. These neuropeptides include brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, nerve growth factor, and ciliary neurotrophic factor [4].
Multimodal Mechanism of Action: Cerebrolysin is considered a peptide substance with a multimodal mechanism of action. The active brain neuropeptides it contains can penetrate the blood-brain barrier and be used by neurons for communication with each other. Its safety, tolerability, and effectiveness have been established in experimental studies and clinical trials. Cerebrolysin is associated with a relatively wide therapeutic time window and can be used as a neuroprotective and neurotrophic agent, helping to delay the progression of brain diseases[4].
Applications in Stroke Treatment:
Effects on Patients with Different Severities: In stroke treatment, early clinical trials were mainly conducted in the mildly affected stroke population, who usually have a good prognosis. However, due to this selection, there may be floor or ceiling effects in the recovery measures for mild cases, making it difficult to show obvious benefits between the treatment groups. In contrast, subgroup analysis of more severely affected patients showed that Cerebrolysin had a significant positive effect on enhancing recovery. Based on the results of multiple studies, it is clear that the magnitude of the effect of Cerebrolysin increases with the severity of the stroke[2].
Combined Use with Thrombolytic Therapy: Other controlled studies have shown that Cerebrolysin can be safely combined with thrombolytic therapy. Recently, Cerebrolysin has been tested not only for its neuroprotective effect but also for its nerve recovery potential and has shown efficacy in patients with moderate to severe stroke[2].
Effect on Functional Recovery: Cerebrolysin has shown benefits in patients with moderate to severe ischemic stroke. When used in combination with neurorehabilitation compared with neurorehabilitation alone, it has a generally significant effect on functional recovery. This provides a direction for more rigorous research designs in the future.
Applications in the Treatment of Acute Ischemic Stroke:
Impact on Mortality and Adverse Events: Moderate-quality evidence suggests that Cerebrolysin may have little beneficial effect on preventing all-cause mortality or the total number of serious adverse events in acute ischemic stroke. At the same time, moderate-quality evidence also suggests that the use of Cerebrolysin may increase the occurrence of non-fatal serious adverse events[8]. Specifically, in the subgroup with a dose of 30 mL for 10 days (cumulative dose of 300 mL), the increase in non-fatal serious adverse events was more significant[8].
Impact on Other Indicators: None of the included trials reported adverse functional outcomes defined as death or dependence at the end of the follow-up period, early death (within two weeks after stroke onset), time to return to work capacity, and quality of life and other indicators. Only one trial clearly reported the causes of death, including cerebral infarction, heart failure, pulmonary embolism, and pneumonia, etc., but there was little difference in the distribution between the Cerebrolysin group and the placebo group[8].
Applications in the Treatment of Cognitive Impairment:
Improving Cognitive Function and Delaying Progression: Cognitive impairment is one of the important issues in modern healthcare. Currently, there are more than 55 million people worldwide suffering from dementia. Dementia is one of the main causes of disability and dependence among the elderly globally. More patients with mild cognitive impairment have an increased risk of progressing to dementia compared with their peers. Due to the impact of COVID-19, the number of patients with cognitive impairment has also increased. Cerebrolysin is a drug that can not only improve cognitive function but also slow down its progression[9].
Applications in Patients with Consciousness Disorders after Stroke:
Improving the Level of Consciousness: A retrospective study showed that Cerebrolysin may improve the level of consciousness of patients in a minimally conscious state after stroke. In this study, patients in a minimally conscious state after ischemic and/or hemorrhagic stroke were studied, and these patients were evaluated according to the Revised Coma Recovery Scale (CRS-R). All patients received comprehensive rehabilitation treatment including physical therapy and occupational therapy. Patients who received Cerebrolysin treatment were compared with those who did not receive Cerebrolysin treatment. The results showed that after adjusting for confounding factors, the Cerebrolysin treatment group had a significant improvement in the CRS-R score, especially in the oral motor and arousal subscales[10].
Applications in Patients with Liver Injury:
Therapeutic Effect on Patients with Liver Injury: For patients with chronic diseases, the treatment of acute life-threatening events is a problem because doctors need to consider the effects of multi-system drugs. Regarding Cerebrolysin, as an amplifier of the Sonic Hedgehog signaling pathway and one of the few approved neurotrophic therapeutic drugs for stroke patients, there is a concern that excessive activation of the Hedgehog pathway may accelerate the progression of non-alcoholic fatty liver disease (NAFLD) to cirrhosis. It has been found that Cerebrolysin clinically improved the aspartate aminotransferase (AST) levels of most stroke patients with liver injury. In the experimental setting, Cerebrolysin was able to reverse anxiety-like behavior in a mouse model of non-alcoholic fatty liver disease but did not improve short-term memory or rescue cell proliferation in the hippocampus after MCD food intake[7].
In conclusion, Cerebrolysin can promote the repair and regeneration of nerve cells, regulate the balance of neurotransmitters to improve signal transmission, provide nutrients for nerve cells and enhance their tolerance to damage, and also promote nerve development. Clinically, cerebrolysin is widely used in the treatment of various nervous system diseases such as brain trauma and sequelae of cerebrovascular diseases, which can improve patients’ symptoms and quality of life. At the same time, it is also an important tool in neuroscience research, which helps to gain an in-depth understanding of the physiological functions of nerve cells and the mechanisms of development and repair of the nervous system, providing theories and ideas for the development of new neuroprotective and repair drugs, and is of great significance in the fields of nervous system disease treatment and neuroscience research.
Scientific Journal Author
Ziganshina L E is a researcher affiliated with several notable institutions. These include the Russian Medical Academy of Continuing Professional Education (RMANPO), Peoples Friendship University of Russia, Kazan State Medical University, Russian Medical Academy of Continuous Professional Education, Ministry of Health of the Russian Federation, Cochrane Russia, Kazan Federal University, Ministry of Health of the Republic of Tatarstan, Kazan State Medical Academy, and SV Kurashov Med Inst. Her institutional connections reflect a strong background in medical and health sciences.
Her research interests span across various subject categories. She has expertise in General & Internal Medicine, Pharmacology & Pharmacy, Public, Environmental & Occupational Health, Neurosciences & Neurology, and Research & Experimental Medicine. Her work in these fields highlights her extensive knowledge and contributions to advancing medical science and healthcare practices. Ziganshina L E is listed in the reference of citation [8].
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