Cerebrolysin Research & Studies

Aging is associated with progressive synaptic deterioration and cognitive decline; however, therapeutic strategies capable of restoring both structural and functional deficits remain limited. This study evaluated the effects of aging on dendritic spine dynamics and recognition memory across multiple brain regions, and evaluated whether chronic treatment with cerebrolysin (CBL) could ameliorate age-related alterations (3, 6, 12 and 18 months of age). We additionally assessed the effects of CBL on key molecular markers of synaptic plasticity in aged (18-month) C57BL6 mice. Aging impaired locomotor activity (12- and 18-month groups) and produced deficits in short- and long-term recognition memory relative to young controls. Notably, CBL selectively enhanced locomotion in 18-month group and improved short-term memory in the 12-month group. At the structural level, aging reduced spine density and decreased the proportion of thin and mushroom spines in the prefrontal cortex and dorsal hippocampus, whereas CBL treatment increased spine density in the dorsal hippocampus and basolateral amygdala, and promoted the formation of mature mushroom spines in a region and age-dependent manner. Importantly, CBL elevated β-actin, synaptophysin and brain-derived nerve factor expression across multiple regions in the 18-month group. This study provides the first integrated demonstration that CBL enhances dendritic spine maturation and dendritic structural remodeling while concurrently improving cognitive outcomes within the same cohort of aged animals. Collectively, our findings position CBL as a promising therapeutic candidate to counteract age-related synaptic loss and cognitive decline, advancing current understanding of neuroprotective interventions in aging.

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.

Subarachnoid Hemorrhage (SAH) is one of the acute neurological conditions that is associated with high mortality and recovery failure rates. In recent years, due to the development of endovascular and classical techniques, the mortality rate after SAH has decreased. Currently, more research is focused on understanding the molecular mechanisms underlying SAH. Methods of treatment are investigated in order to obtain the best treatment result, not only survival. One of the drugs used in stroke, including SAH, is Cerebrolysin. It is a mixture of neuropeptides that has similar properties to neurotrophic factors. Its positive impact on strokes has been analyzed; however, there are no meta-analyses concerning only the subpopulation of patients diagnosed with SAH in the current literature. Therefore, we conducted a meta-analysis of available clinical trials to evaluate the effect of Cerebrolysin on the treatment outcome. The data suggest a positive effect of Cerebrolysin on the mortality of SAH patients. However, further randomized clinical trials with larger groups of patients are needed to draw final conclusions.

TBI (traumatic brain injury) is one of the most common causes of deaths and failure to return to society according to the latest statistics. Cerebrolysin is a drug approved for use in patients diagnosed with TBI. It is a mixture of neuropeptides derived from purified porcine brain proteins and multiple experimental studies have proven its neuroprotective and neurorestorative properties both in vitro and in vivo. In our meta-analysis, we analyze the latest clinical study reports on the use of Cerebrolysin in patients with TBI. The authors searched the databases: Pub Med, Cinahl, Web Of Science, and Embase from database inception until 11th July 2022. Ten clinical studies were eligible and included in the final analysis, including both retrospective and prospective studies of 8749 patients. Treatment with Cerebrolysin was associated with a statistically significant change in GCS and GOS. Mortality of any cause and the length of stay was not affected by the treatment. Our findings support and confirm the beneficial effects of Cerebrolysin treatment on the clinical outcome of patients after TBI. Further multi-center studies to optimize dosing and time of administration should be conducted.

Cerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from porcine brain, which has potential neuroprotective properties. It is widely used in the treatment of acute ischaemic stroke in Russia, Eastern Europe, China, and other Asian and post-Soviet countries. This is an update of a review first published in 2010 and last updated in 2020.

Cerebrolysin therapy has the potential to significantly aid in the treatment of a wide variety of debilitating neurological diseases including ischemic strokes, neurodegenerative disorders, and traumatic brain injuries. Although Cerebrolysin is not approved for use in the USA, it is used clinically in over 50 countries worldwide. In this review, we focus on outlining the role that Cerebrolysin has in stimulating the molecular signaling pathways that are critical for neurological regeneration and support. An extensive evaluation of these signaling pathways reveals that Cerebrolysin has the potential to intervene in a diverse array of pathophysiological causes of neurological diseases. In the clinical setting, Cerebrolysin is generally safe for human use and has provided functional improvement when used as an adjunct treatment. However, our literature review revealed inconsistent results, as several clinical studies suggested that Cerebrolysin treatment has minor clinical relevance and did not have significant advantages over a placebo. In conclusion, we found that Cerebrolysin therapy can potentially play a major role in the treatment of many neurological diseases. Nevertheless, there remains much to be elucidated about the efficacy of this treatment for specific neurological conditions, and more robust clinical data is needed to reach a consensus and properly define the therapeutic role of Cerebrolysin.

Parkinson's disease (PD) is affecting >10 million people worldwide for which no suitable cure has been developed so far. Roughly, about two people per thousand populations are affected with PD like symptoms especially over the age of 50. About 1% of the populations above 60 years suffer from PD-like disease. The prevalence of the disease is increasing over the years, and future projections by 2020 could be 12-14 millions people affected by the disease. Thus, exploration of suitable therapeutic measures is the need of the hour to enhance quality of the life of PD patients. PD induced brain pathology includes loss of dopaminergic neurons in the substantia niagra that could later extends to other cortical regions causing loss of voluntary motor control. Deposition of α-synuclein in the brain further leads to neurodegeneration. However, the exact cause of PD is still unknown. It appears that breakdown of the blood-brain barrier (BBB) and leakage of serum component into the brain could lead to neurodegeneration in PD. Thus, novel treatment strategies that are able to restore BBB breakdown and enhance neuronal plasticity and neuroregeneration in PD could be effective in future therapy. With the advancement of nanotechnology, it is worthwhile to understand the role of nanodelivery of selected agents in PD to enhance neuroprotection. In this review new role of BBB, brain edema, and neuropathology in PD is discussed. In addition, superior neuroprotection induced by nanowired delivery of a multimodal drug cerebrolysin in PD is summarized based on our own investigations.

To establish the molecular mechanisms of the mood stabilizing (normothymic) action of the neuroprotector Cerebrolysin.

Although vascular dementia is the second most common cause of dementia globally, evidence-based treatments are still lacking. Cerebrolysin is a porcine brain-derived preparation that is said to have neurotrophic and neuroprotective activity. In many parts of the world Cerebrolysin, given as a series of daily intravenous infusions, is used as a potential intervention for vascular dementia. A previous Cochrane Review on Cerebrolysin in vascular dementia yielded inconsistent results. We wished to update the review to add new studies from the international literature and employ contemporary methods for appraising the strength of the evidence. This is the first update of a review first published in 2013.

Cerebrolysin is a neuropeptide preparation with neurotrophic effects and promotes recovery after brain injury. Its preclinical profile promises wide applications due to its multi-target effects. Currently, Cerebrolysin is used for treatment of cerebral ischemia and neurodegeneration. Areas covered: In stroke, earlier clinical trials with Cerebrolysin were performed mostly in mildly affected stroke populations, which usually have a favorable prognosis. Due to this selection, a floor or ceiling effect of recovery measures in the mild cases may have prevented to show a clear benefit between treatment groups. In contrast, subgroup analyses of more severely affected patients reveal a strikingly positive effect for enhanced recovery. Based on the findings from several studies, it became evident that the effect size of Cerebrolysin was increasing with stroke severity. Other controlled studies showed that Cerebrolysin can be safely used in combination with thrombolysis. More recently, Cerebrolysin has been tested not only for neuroprotection but also for its neurorecovery potential and also showed efficacy in patients with moderate to severe strokes. Expert commentary: Cerebrolysin shows a benefit mostly in moderate to severe ischemic stroke patients and an overall significant effect for functional recovery when combined with neurorehabilitation versus neurorehabilitation alone. This gives lead to the planning of a more rigorous study design in the future.

The review discusses existing evidence of benefits and risks of cerebrolysin--a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue with proposed neuroprotective and neurotrophic properties, for acute ischemic stroke. The review presents results of systematic search and analysis of randomised clinical trials comparing cerebrolysin with placebo in patients with acute ischemic stroke. Only one trial was selected as meeting quality criteria. No difference in death and adverse events between cerebrolysin and placebo was established. The authors conclude about insufficiency of evidence to evaluate the effect of cerebrolysin on survival and dependency in people with acute ischemic stroke.

Cerebrolysin is a neuropeptide preparation mimicking the action of endogenous neurotrophic factors. Positive effects of Cerebrolysin on β-amyloid- and tau-related pathologies, neuroinflammation, neurotrophic factors, oxidative stress, excitotoxicity, neurotransmission, brain metabolism, neuroplasticity, neuronal apoptosis and degeneration, neurogenesis and cognition were demonstrated in experimental conditions. These pleiotropic effects of Cerebrolysin on Alzheimer's disease-related pathogenic events are consistent with a neurotrophic-like mode of action, and seems to involve the activation of the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase-3 β intracellular signaling pathway. The clinical efficacy of Cerebrolysin in Alzheimer's disease was evaluated in several randomized, double-blind, clinical trials, showing consistent benefits on global clinical function and cognition, improvements in behavior at high doses, and minor effects on daily living activities in patients with mild to moderate Alzheimer's disease, as well as in subgroups of moderate to moderately severe patients. In addition, the clinical benefits of Cerebrolysin were largely maintained for several months after ending treatment, a finding that supports its discontinuous administration. Cerebrolysin was generally well tolerated and did not induce significant adverse events in Alzheimer's patients. Although long-term studies are needed, the data available suggest that Cerebrolysin is effective as monotherapy and constitutes a promising option for combined therapy in Alzheimer's disease.

Cerebrolysin is a parenterally administered, porcine brain-derived peptide preparation that has pharmacodynamic properties similar to those of endogenous neurotrophic factors. In several randomized, double-blind trials of up to 28 weeks' duration in patients with Alzheimer's disease, Cerebrolysin was superior to placebo in improving global outcome measures and cognitive ability. A large, randomized comparison of Cerebrolysin, donepezil or combination therapy showed beneficial effects on global measures and cognition for all three treatment groups compared with baseline. Although not as extensively studied in patients with vascular dementia, Cerebrolysin has also shown beneficial effects on global measures and cognition in this patient population. Cerebrolysin was generally well tolerated in clinical trials, with dizziness (or vertigo) being the most frequently reported adverse event. Although further studies with Cerebrolysin, including longer term trials and further exploration of its use in combination with cholinesterase inhibitors, are needed to more clearly determine its place in the management of Alzheimer's disease and vascular dementia, available data suggest that Cerebrolysin is a useful addition to the treatment options available for dementia.