Cerebrolysin

Retraction Note: Neurotrophic effects of Cerebrolysin in the Mecp2308/Y transgenic model of Rett syndrome.

Edith Doppler, Edward Rockenstein, Kiren Ubhi +7 more

[The effect of neuroprotectors on the level of BDNF, tumor necrosis factor alpha and apoptosis markers, and in acute cerebrovascular accidents].

A V Shchulkin, I V Chernykh, Y V Abalenikhina +5 more

To compare the effects of Mexidol, Cerebrolysin, and Cortexin on the levels of brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNFα), and apoptosis markers in the rat brain following middle cerebral artery (MCA) occlusion-reperfusion.

Microglial Polarization and Therapeutic Strategies in Post-stroke Neuroinflammation.

Travis Yui Hei Chan, Brian De Yu Ma, Timothy Keith Hung +2 more

Stroke remains a leading cause of global disability, perpetuated by maladaptive neuroinflammation that drives secondary injury and impairs recovery. An early reparative (M2) state rapidly transitions into a dominant destructive (M1) phenotype within days, worsening tissue damage through the release of cytokines [tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6)], blood-brain barrier disruption, and amplified peripheral immune cell infiltration. Emerging pharmacological interventions, such as the free radical scavenger edaravone, the neurotrophic factor cerebrolysin, and the excitotoxicity modulator citicoline, demonstrate promising neuroprotective potential when strategically timed. Additionally, novel non-pharmacological approaches, including repetitive transcranial magnetic stimulation, stem cell therapy, and nanoparticle-based drug delivery, offer innovative pathways for targeting neuroinflammation. However, translational challenges persist, including narrow therapeutic windows, biomarker heterogeneity, and preclinical-to-clinical gaps. Future progress necessitates precision medicine paradigms integrating spatiotemporal drug delivery, biomarker-guided intervention timing, and synergistic combinatorial regimens targeting acute injury and chronic repair phases. By bridging mechanistic insights with clinical applications, this review delineates neuroinflammatory modulation as a pivotal frontier for redefining stroke recovery while outlining essential research trajectories to overcome existing barriers. Systematic search of electronic databases including PubMed, Web of Science, Embase, and Cochrane (1996-2025) was performed, with eligible studies assessed using PRISMA guidelines. Findings on neuroinflammation, mechanism, or interventions in ischemic stroke were narratively synthesized through thematic analysis. This review summarizes current insights into post-stroke neuroinflammatory mechanisms, with a focus on the dual role of microglial polarization.

Safety and Efficacy of Cerebrolysin for Neurorecovery After Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of 14 Randomized Controlled Trials.

Parag N Patel, Devang Mangal, Krunal Patel

Cerebrolysin, a neurotrophic compound, has been investigated as a neurorestorative therapy in acute ischemic stroke, although findings are inconsistent due to limitations in study inclusion and outcome reporting. This systematic review and meta-analysis evaluated the efficacy and safety of Cerebrolysin in improving neurological and functional outcomes following acute ischemic stroke. Fourteen randomized controlled trials (N = 2,884 patients) comparing Cerebrolysin to placebo were included. The primary outcome was change in the National Institutes of Health Stroke Scale (NIHSS) score from baseline to follow-up, while secondary outcomes included functional independence (modified Rankin Scale (mRS) 0-2), serious adverse events (SAEs), mortality, and hemorrhagic transformation. Risk of bias was assessed using the revised Cochrane Risk of Bias (RoB 2.0) tool, and certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. Pooled analysis showed that Cerebrolysin significantly improved neurological recovery (mean difference in NIHSS change: +1.39; 95% confidence interval (CI): 0.53-2.25; p = 0.020). Functional independence showed a non-significant trend in favor of Cerebrolysin (risk ratio (RR) = 1.31; 95% CI: 0.90-1.91; p > 0.05). No significant differences were observed in SAEs (RR = 1.08; 95% CI: 0.84-1.40), mortality (RR = 0.86; 95% CI: 0.68-1.09), or hemorrhagic transformation (RR = 0.55; 95% CI: 0.32-0.92). These findings suggest that Cerebrolysin significantly enhances early neurological recovery after ischemic stroke, with a comparable safety profile. Further high-quality trials are warranted to confirm its impact on long-term functional outcomes.

Evaluating the Effect of Cerebrolysin as an Adjuvant to Standard Therapy in Patients with Acute Ischemic Stroke: A Prospective Observational Study.

Geetha Kandasamy, Vijayakumar Arumugam, Khalid Orayj +4 more

Background and Objectives: Acute ischemic stroke is a major cause of disability and mortality. Cerebrolysin, a neuropeptide with neuroprotective and neurotrophic properties, may enhance post-stroke recovery. This study evaluated the impact of adding Cerebrolysin to standard therapy on clinical outcomes in patients with acute ischemic stroke. Materials and Methods: This non-randomized prospective observational study included 143 adults with acute ischemic stroke at Kovai Medical Center and Hospital, Coimbatore (April 2016-May 2018). Participants were divided into two groups: the standard therapy group (n = 70) and the adjuvant therapy group (n = 73), which received Cerebrolysin (30 mL IV daily for 14 days) in addition to standard care. Stroke severity and functional outcomes were evaluated using the National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI) at baseline and Day 14. A p < 0.05 was considered statistically significant. Results: Stroke severity improved in both groups, but the adjuvant group demonstrated significantly greater reductions in NIHSS scores from 9.90 ± 2.90 to 3.40 ± 1.40 compared to the standard group, which improved from 10.10 ± 2.80 to 4.80 ± 1.30 (t = 6.19, p < 0.001). Additionally, 43.84% of patients in the adjuvant group shifted to minor stroke severity versus 25.71% in the standard group. Both groups showed significant improvements across all domains of the BI, which assesses activities of daily living (ADL); however, the gains were consistently greater in the adjuvant group (p < 0.001). A higher proportion of patients in the Cerebrolysin group achieved slight dependency (38.36%) or full independence (16.44%), compared to 20% and 5.71% in the standard group, respectively. Conclusions: This prospective observational study suggests that adding Cerebrolysin to standard therapy was associated with greater neurological recovery and functional independence in acute ischemic stroke patients. However, the short follow-up, single-center setting, and lack of randomization limit generalizability. Larger multicenter randomized trials with longer follow-up are needed to confirm these findings.

Influence of Exogenous Neuropeptides on the Astrocyte Response Under Conditions of Continuous and Cyclic Hypoxia and Red Blood Cell Lysate.

Klaudyna Kojder, Magdalena Gąssowska-Dobrowolska, Wojciech Żwierełło +7 more

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.

Cerebrolysin Induces Dendritic Tree Plastic Changes and BDNF Increase in the Amygdala of Male Rats with Maternal Deprivation.

Jhonathan Cárdenas-Bedoya, Blanca Miriam Torres-Mendoza, Nestor Ismael Martínez-Torres

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.

The possible role of cerebrolysin in the management of vascular dementia: Leveraging concepts.

Hayder M Al-Kuraishy, Ali I Al-Gareeb, Salwa H Zekry +4 more

Cerebrolysin (CBL) is a combination of neurotrophic peptides and amino acids derived from pig brains. CBL can cross the blood-brain barrier (BBB) and its biological effect is similar to the effect of endogenous neurotrophic effects. The mechanism of action of CBL is related to the induction of neurogenesis, neuroplasticity, neuroprotection, and neurotrophicity. Therefore, CBL may be effective against the development and progression of neurodegenerative diseases such as Alzheimer disease (AD) and cerebrovascular disorders such as vascular dementia (VD). Moreover, many studies highlighted that CBL is effective in the improvement of cognitive impairment in patients with neurodegenerative diseases. However, the underlying neuroprotective effects of CBL against the VD neuropathology were not fully elucidated. Thus, this review aims to discuss the possible therapeutic efficacy of CBL in the management of VD. In conclusion, CBL could be effective therapeutic strategy in preventing and treating VD by targeting neuroinflammation, BBB injury, and chronic cerebral hypoperfusion.

Speech Therapy Combined With Cerebrolysin in Enhancing Nonfluent Aphasia Recovery After Acute Ischemic Stroke: ESCAS Randomized Pilot Study.

Volker Homberg, Dragoș Cătălin Jianu, Adina Stan +7 more

Stroke-induced aphasia significantly impacts communication and quality of life. Despite the standard treatment being speech and language therapy, outcomes vary, highlighting the need for additional therapies. Cerebrolysin, a neuroprotective and neurotrophic agent, has shown potential in stroke management. This study addresses the notable gap in research about the combined use of Cerebrolysin and speech therapy, evaluating their synergistic potential in the treatment of aphasia.

[Effect of neurofeedback training on relative α variant score monitored by bedside continuous electroencephalography and optic nerve sheath diameter evaluated by ultrasound in patients with ischemic hypoxic encephalopathy].

Jie Sun, Jian Wan

To approach the evaluation of relative α variant score monitored by bedside continuous electroencephalography and optic nerve sheath diameter (ONSD) evaluated by ultrasound in patients with ischemic hypoxic encephalopathy, and to observe the effect of neurofeedback training on brain function.

Cerebrolysin treatment improved short-term memory deficits while simultaneously increasing hippocampal spine density in hypertensive female rats.

Ivette Espinoza, Ma de Jesús Gómez-Villalobos, Leonardo Aguilar-Hernández +2 more

Hypertension, if untreated, can disrupt the blood-brain-barrier (BBB) and reduce cerebral flow in the central nervous system (CNS) inducing hippocampal atrophy, potentially leading to cognitive deficits and vascular dementia. Spontaneous hypertensive rats (SHR) demonstrated neuroplastic alterations in the hippocampus, hyperlocomotion and memory deficits in males. Cerebrolysin (CBL), a neuropeptide preparation, induces synaptic and neuronal plasticity in various populations of neurons and repairs the integrity of the BBB. This research aims to investigate the behavioral outcomes in locomotion and recognition memory in the Novel Object Recognition Test (NORT) and assess the neuroreparative effect of CBL on the cytoarchitecture of neurons and the spine density in pyramidal neurons of the prefrontal cortex (PFC), the entorhinal cortex (EC) and the CA1 region of the dorsal hippocampus, as well as spheroidal neurons of the dentate gyrus (DG). Our findings indicate that SHR exhibited elevated diastolic and systolic pressures, and increased locomotion. Importantly, CBL treatment improved recognition memory in SHR strain. Hypertension led to reduced arborization in the EC, CA1, and DG regions. Moreover, CBL treatment increased arborization in both normotensive and hypertensive rats in the CA1, and DG regions of hippocampus and EC and selectively increased spine density in the hippocampus of hypertensive rats. These findings suggest that CBL neurotrophic treatment enhances recognition memory and promotes dendritic growth or spine density, depending on the neurochemical environment within the brain.

Neuroprotective and neuroregenerative drugs after severe traumatic brain injury : A narrative review from a clinical perspective.

Ivan Grgac, Guenther Herzer, Wolfgang G Voelckel +2 more

Traumatic brain injuries cause enormous individual and socioeconomic burdens. Survivors frequently struggle with motor handicaps as well as impaired cognition and emotion. In addition to the primary mechanical brain damage, complex secondary mechanisms are the main drivers of functional impairment. Many of these pathophysiological mechanisms are now well known: excitotoxic amino acids, breakdown of the blood-brain barrier, neuroinflammation with subsequent damage to cell organelles and membranes, cerebral edema, and apoptotic processes triggering neuronal death; however, paracrine resilience factors may counteract these processes. Specific neuroprotective and neuroregenerative intensive care therapies are few. This review highlights medical approaches aimed at mitigating secondary damage and promoting neurotrophic processes in severe traumatic brain injury. Some pharmacologic attempts that appeared very promising in experimental settings have had disappointing clinical results (progesterone, cyclosporine A, ronopterin, erythropoietin, dexanabinol). Thus, the search for drugs that can effectively limit ongoing posttraumatic neurological damage is ongoing. Some medications appear to be beneficial: N‑methyl-D-aspartate receptor (NMDA) antagonists (esketamine, amantadine, Mg++) reduce excitotoxicity and statins and cerebrolysin are known to counteract neuroinflammation. By supporting the impaired mitochondrial energy supply, oxidative processes are inhibited and neuroregenerative processes, such as neurogenesis, angiogenesis and synaptogenesis are promoted by citicoline and cerebrolysin. First clinical evidence shows an improvement in cognitive and thymopsychic outcomes, underlined by own clinical experience combining different therapeutic approaches. Accordingly, adjuvant treatment with neuroprotective substances appears to be a promising option, although more randomized prospective studies are still needed.

Cerebrolysin Induces Motor Recovery Along with Plastic Changes in Motoneurons and an Increase in GAP43 Protein in the Ventral Spinal Cord Following a Kainic Acid Excitotoxic Lesion in the Rat Motor Cortex.

Nestor I Martínez-Torres, Jhonathan Cárdenas-Bedoya, Blanca Miriam Torres-Mendoza

Lesions in the motor cortex induced by contusions or pathological insults can exert the degeneration of afferent neurons lying distal to these lesions. Axon degeneration and demyelination are hallmarks of several diseases sharing pathophysiological and clinical characteristics. These conditions are very disabling due to the disruption of motor abilities, with lesions that affect this area proving to be a therapeutic challenge, which has driven increasing efforts to search for treatments. Cerebrolysin (CBL) contains a mix of pig brain-derived peptides with activity similar to neurotrophic factors. Here, the effect of cerebrolysin administration on the motor impairment produced by kainic acid (KA) lesion of the motor cortex was evaluated in Sprague-Dawley female rats (n = 27), defining its effect on motoneurons dendritic tree changes, dendritic spine density and GAP43 presence in the ventral thoracolumbar regions of the spinal cord. Ten days after the KA lesion of the motor cortex, rats were administered cerebrolysin, and their motor performance was evaluated using the "Basso, Beattie, and Bresnahan" (BBB) and Bederson scores. Cerebrolysin administration improved motor activity according to the BBB and Bederson scales, along with increased dendritic intersections and dendritic spine density on motoneurons. There was also a significant increase in GAP43 protein, suggesting that CBL may promote plastic changes through this protein, among others. Hence, this study proposes that cerebrolysin could promote motor recovery following motor cortex lesions by driving neuronal changes and dendritic spine plasticity on motoneurons and an increase in GAP43 protein, along with other mechanisms.

Cerebrolysin in Patients with Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis.

Klaudyna Kojder, Konrad Jarosz, Mateusz Bosiacki +4 more

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.

Cerebrolysin Concentrate: Therapeutic Potential for Severe Oral Apraxia After Stroke: A Case Report.

Hyeonwoo Jeon, Doo Young Kim

Cerebrolysin concentrate is a medication whose main active ingredient is brain-derived neurotrophic factor. It has been reported to help in the restoration of cognitive function and overall physical function after brain injuries. We present the case of a 72-year-old man with severe oral apraxia due to a left middle cerebral artery ischemic stroke involving the left insular cortex. He was being tube fed due to severe oral apraxia with cognitive decline that made it difficult for him to even imitate simple oral movements. The patient initially had impaired consciousness and cognitive function. He also had limited physical activity due to acute stroke complications, such as hemorrhagic transformation of cerebral infarction, and required bed rest until 23 days after onset. The patient received intravenous cerebrolysin concentrate in addition to intensive rehabilitation therapy from 23 days after onset. After rehabilitation and administration of cerebrolysin concentrate, there was a marked recovery within a short period of time to the point where oral intake of a regular diet was possible, indicating a significant improvement in oral apraxia. It is a notable example of the potential therapeutic effect of cerebrolysin concentrate for post-stroke oral apraxia.

Life-Threatening Anaphylaxis due to Cerebrolysin®.

Helmut Trimmel, Wolfgang Tauber, Martin Zikeli

In this case report, we describe a well-documented, severe anaphylactic reaction after intravenous administration of cerebrolysin, a neurotrophic agent derived from highly purified porcine brain tissue, consisting of peptides and free amino acids. Cerebrolysin has been in use for decades, in various neurological diseases, but especially stroke and traumatic brain injury, with the aim of enhancing cognitive performance. After administration of cerebrolysin to an 85-year-old male patient suffering from subacute stroke, he developed a fulminant anaphylactic reaction. Following institutional standards, vital functions were quickly restored. The anaphylactic reaction was clearly confirmed by laboratory tests. To date, only rare cases of anaphylaxis due to cerebrolysin have been published in the literature. The current report is intended to raise awareness for the possibility of such a reaction, given the widespread use of cerebrolysin in several indications in mostly critical patients. The case shows how a completely unexpected life-threatening situation can be successfully treated by targeted measures, if the situation is recognized quickly. In light of this event, we consider pathophysiology of allergic reactions and treatment guidelines.

QEEG indices in traumatic brain injury - insights from the CAPTAIN RTMS trial.

Verişezan Roşu Olivia, Diana Chira, Vlad-Florin Chelaru +4 more

This secondary analysis of the CAPTAIN-RTMS trial data focused on the significance of quantitative electroencephalography (qEEG) indices as indicators of recovery in patients with traumatic brain injury (TBI). By focusing on the delta alpha ratio (DAR), delta theta/alpha beta ratio (DTABR), and theta beta ratio (TBR), this study explored the shifts in brainwave activity as a response to an integrative treatment regimen of repetitive transcranial magnetic stimulation (rTMS) combined with the neurotrophic agent Cerebrolysin. Findings revealed significant increases in DAR and DTABR, suggesting changes in neurophysiological dynamics after treatment. However, variations in TBR were inconclusive in providing clear electrophysiological insights. These results indicate that further research is necessary to describe and understand the underlying mechanisms of brain recovery and to develop refined treatment frameworks for patients with TBI.

[Cognitive impairment in post-traumatic stress disorder].

A N Bogolepova

Post-traumatic stress disorder (PTSD) is a common mental health disorder, with an incidence of up to 12.5% among primary care patients. Most often, PTSD is detected in combat veterans, victims of terrorist attacks and terror, but it can also be a consequence of traumatic brain injury and medical interventions. Impaired cognitive functioning is a key feature of PTSD, including attention deficits and reduced processing speed, executive dysfunction, and impairments in verbal learning and memory. Cognitive impairments in PTSD are significantly persistent and are largely similar in nature to neuropsychological impairments in neurodegenerative pathology. Possible pathogenetic mechanisms underlying PTSD are the development of neuroinflammation, oxidative stress and decreased production of neurotrophic factors. One of the promising areas of treatment is the use of Cerebrolysin, which has powerful neurotrophic and anti-inflammatory activity.

Acute Combined Cerebrolysin and Nicotinamide Administration Promote Cognitive Recovery Through Neuronal Changes in the Hippocampus of Rats with Permanent Middle Cerebral Artery Occlusion.

Nestor I Martínez-Torres, Jhonathan Cárdenas-Bedoya, Blanca Miriam Torres-Mendoza

Stroke is one of the leading causes of disability worldwide, where the Hippocampus (HPC) is affected. HPC organizes memory, which is a cognitive domain compromised after a stroke, where cerebrolysin (CBL) and Nicotinamide (NAM) have been recognized as potentially therapeutic. In this study, we aimed to evaluate the efficacy of a combined administration of CBL and NAM in a rat stroke model. Male Sprague-Dawley rats (n = 36) were divided into four groups: saline (pMCAO - Saline), CBL (pMCAO + CBL), NAM (pMCAO + NAM), and experimental (pMCAO + CBL-NAM) (n = 9 per group). A permanent middle cerebral artery occlusion (pMCAO) was induced through electrocauterization of the middle cerebral artery, followed by the administration of CBL (2.5 ml/kg), NAM (500 mg/kg) or combined immediately after skin suture, as well as at 24, 48, and 72 h post-surgery. The rats were evaluated in the novel object recognition test; hippocampal infarct area measurement; reconstruction of neurons from CA1 for Sholl analysis; and, measurement of brain-derived neurotrophic factor (BDNF) levels near the infarct zone. Our findings revealed that the administration of CBL or NAM induced infarct reduction, improved cognition, and increased BDNF levels. Moreover, a combination of CBL and NAM increased dendritic intersection in CA1 pyramidal neurons. Thus, the combined administration of CBL and NAM can promote cognitive recovery after a stroke, with infarct reduction, cytoarchitectural changes in HPC CA1 neurons, and BDNF increase. Our findings suggest that this combination therapy could be a promising intervention strategy for stroke.

Comparing the biological activity and composition of Cerebrolysin with other peptide preparations.

Lisa-Franziska Seidl, Ludwig Aigner

Neurological disorders, ranging from acute forms such as stroke and traumatic brain injury to neurodegenerative diseases like dementia, are the leading cause of disability-adjusted life years (DALYs) worldwide. A promising approach to address these conditions and promote nervous system regeneration is the use of the neuropeptide preparation Cerebrolysin, which has been shown to be effective in both clinical and preclinical studies. Despite claims of similar clinical efficacy and safety by several peptide preparations, concerns regarding their generic composition and efficacy have been previously raised. Based on these reports, we analyzed the peptide composition and neurotrophic activity of several peptide preparations allegedly similar to Cerebrolysin and approved in some countries for treating neurological diseases. Our results demonstrate that these preparations lack relevant biological activity and that the peptide composition is significantly different from Cerebrolysin. peptide.

Cerebrolysin potentiates the antidepressant effect of lithium in a rat model of depression.

Ahmed O Abdelaty, Engy K Tharwat, Alaa I Abdelrahman +13 more

Depression is the most prevalent psychiatric disorder worldwide. Although numerous antidepressant treatments are available, there is a serious clinical concern due to their severe side effects and the fact that some depressed patients are resistant to them. Lithium is the drug of choice for bipolar depression and has been used as adjunct therapy with other groups of antidepressants.

Neuroprotection by Cerebrolysin and Citicoline Through the Upregulation of Brain-Derived Neurotrophic Factor (BDNF) Expression in the Affected Neural Cells: A Preliminary Clue Obtained Through an In Vitro Study.

Anandan P, Santhanam Rengarajan, Sankar Venkatachalam +5 more

Citicoline and cerebrolysin are two unique yet contentious medications because of inconsistencies in efficacy as well as the mystery surrounding their mode of action. The current study aimed to re-validate the neuroprotective benefits of these medications and investigate the possible molecular mechanism.

A Neurofilament-L reporter cell line for the quantification of early neuronal differentiation: A Bioassay for neurotrophic activities.

Lisa-Franziska Seidl, Stefan Winter, Ludwig Aigner +1 more

Neurotrophic activity constitutes a crucial factor in the recovery from neurological injuries and is impaired in neurodegenerative disorders. Preclinical studies of neurotrophic factors to improve outcome of neurodegenerative diseases have yielded promising results. However, due to the complexity of these therapies, the clinical translation of this approach was so far not successful and more feasible treatments with neurotrophic activity may be promising alternatives. Therefore, highly sensitive and robust assays for compound screening are required.

Cerebrolysin provides effective protection on high glucose-induced neuropathy in cultured rat dorsal root ganglion neurons.

Ugur Yazar, Ali Rıza Guvercin, Mahindokht Rouhikia +4 more

Cerebrolysin, an endogenous peptide with neuroprotective and neurotrophic properties, indicated to be beneficial on diabetic neuropathy by preliminary clinical and experimental studies but without evidence on central or peripheral action. Dorsal root ganglion (DRG) neurons, based on involvement of pain sensation in both health and disease as first relay centers for transmission and processing of peripheral nociceptive sensory signals, was used to investigate possible effects of Cerebrolysin on high glucose-induced neuropathy, as model. DRG's were obtained from adult rats and the isolated neurons were seeded on E-Plate®'s equipped with gold microelectrodes, and incubated in culture media in a CO2 incubator at 37 C. DRGs were exposed to high glucose (50 mM) in the absence and presence of different concentrations of Cerebrolysin ® (2-40 mg/ml). Cell index (derived from cell viability and neurite outgrowth) was recorded with Real-Time Cell Analyzer and was used as primary outcome measure. High glucose-induced cellular neuropathy and neuroprotective effects of Cerebrolysin was evaluated from area under the curve (AUC) of cell index-time graphs. Exposure of DRG neurons to high glucose caused a rapid and persistent decrease in the mean AUC values compared to normoglycemic controls. Co-treatment with Cerebrolysin (40 mg/ml) attenuated this high glucose-induced effect in a concentration-dependent manner. In normoglycemic conditions, treatment with Cerebrolysin caused a dose-dependent increase in the mean AUC values. Cerebrolysin treatment resulted in maintenance of the functional integrity, survival, and promotion of neurite outgrowth of the cultured DRG neurons exposed to high glucose, indicating involvement of peripheral sensory neurons.

Heterogeneous treatment effects of Cerebrolysin as an early add-on to reperfusion therapy: post hoc analysis of the CEREHETIS trial.

Mikhail N Kalinin, Dina R Khasanova

Background: There has been intensive research into enhancing the effects of reperfusion therapy to mitigate hemorrhagic transformation (HT) in stroke patients. Using neuroprotective agents alongside intravenous thrombolysis (IVT) appears a promising approach. Cerebrolysin is one of the candidates since it consists of neuropeptides mimicking the action of neurotrophic factors on brain protection and repair. Objectives: We looked at treatment effects of Cerebrolysin as an early add-on to IVT in stroke patients with varying HT risk. Methods: It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744). Patients with middle cerebral artery infarction (n = 238) were selected from the intention-to-treat population. To stratify participants according to their HT risk, the DRAGON, SEDAN and HTI scores were computed for each eligible subject using on-admission data. The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90. Favorable functional outcome (FFO) was defined as an mRS ≤2. The performance of each stratification tool was estimated with regression approaches. Heterogeneous treatment effect analysis was conducted using techniques of meta-analysis and the matching-smoothing method. Results: The HTI score outperformed other tools in terms of HT risk stratification. Heterogeneity of Cerebrolysin treatment effects was moderate (I2, 35.8%-56.7%; H2, 1.56-2.31) and mild (I2, 10.9%; H2, 1.12) for symptomatic and any HT, respectively. A significant positive impact of Cerebrolysin on HT and functional outcome was observed in the moderate (HTI = 1) and high (HTI ≥2) HT risk patients, but it was neutral in those with the low (HTI = 0) risk. In particular, there was a steady decline in the rate of symptomatic (HTI = 0 vs. HTI = 4: by 4.3%, p = 0.077 vs. 21.1%, p < 0.001) and any HT (HTI = 0 vs. HTI = 4: by 1.2%, p = 0.737 vs. 32.7%, p < 0.001). Likewise, an mRS score reduction (HTI = 0 vs. HTI = 4: by 1.8%, p = 0.903 vs. 126%, p < 0.001) with a reciprocal increase of the fraction of FFO patients (HTI = 0 vs. HTI = 4: by 1.2% p = 0.757 vs. 35.5%, p < 0.001) was found. Conclusion: Clinically meaningful heterogeneity of Cerebrolysin treatment effects on HT and functional outcome was established in stroke patients. The beneficial effects were significant in those whose estimated on-admission HT risk was either moderate or high.

The effectiveness of cerebrolysin, a multi-modal neurotrophic factor, for treatment of post-covid-19 persistent olfactory, gustatory and trigeminal chemosensory dysfunctions: a randomized clinical trial.

Sherifa Ahmed Hamed, Mohamed Azzam Abdel-Razek Ahmed

This trial aimed to monitor the outcomes of persistent post-covid-19 smell and taste disorders after cerebrolysin therapy, a NTF, and olfactory and gustatory trainings.

Spinal cord injury induced exacerbation of Alzheimer's disease like pathophysiology is reduced by topical application of nanowired cerebrolysin with monoclonal antibodies to amyloid beta peptide, p-tau and tumor necrosis factor alpha.

Aruna Sharma, Lianyuan Feng, Dafin F Muresanu +6 more

Hallmark of Alzheimer's disease include amyloid beta peptide and phosphorylated tau deposition in brain that could be aggravated following traumatic of concussive head injury. However, amyloid beta peptide or p-tau in spinal cord following injury is not well known. In this investigation we measured amyloid beta peptide and p-tau together with tumor necrosis factor-alpha (TNF-α) in spinal cord and brain following 48 h after spinal cord injury in relation to the blood-spinal cord and blood-brain barrier, edema formation, blood flow changes and cell injury in perifocal regions of the spinal cord and brain areas. A focal spinal cord injury was inflicted over the right dorsal horn of the T10-11 segment (4 mm long and 2 mm deep) and amyloid beta peptide and p-tau was measured in perifocal rostral (T9) and caudal (T12) spinal cord segments as well as in the brain areas. Our observations showed a significant increase in amyloid beta peptide in the T9 and T12 segments as well as in remote areas of brain and spinal cord after 24 and 48 h injury. This is associated with breakdown of the blood-spinal cord (BSCB) and brain barriers (BBB), edema formation, reduction in blood flow and cell injury. After 48 h of spinal cord injury elevation of amyloid beta peptide, phosphorylated tau (p-tau) and tumor necrosis factor-alpha (TNF-α) was seen in T9 and T12 segments of spinal cord in cerebral cortex, hippocampus and brain stem regions associated with microglial activation as seen by upregulation of Iba1 and CD86. Repeated nanowired delivery of cerebrolysin topically over the traumatized segment repeatedly together with monoclonal antibodies (mAb) to amyloid beta peptide (AβP), p-tau and TNF-α significantly attenuated amyloid beta peptide, p-tau deposition and reduces Iba1, CD68 and TNF-α levels in the brain and spinal cord along with blockade of BBB and BSCB, reduction in blood flow, edema formation and cell injury. These observations are the first to show that spinal cord injury induces Alzheimer's disease like symptoms in the CNS, not reported earlier.

[Cognitive impairment and tactics of using the drug Cerebrolysin. Resolution of the International Council of Experts (May 12, 2023)].

O S Levin, I A Voznyuk, S N Illarioshkin +11 more

The aging of the population and the associated increase in the share of cognitive impairments in the structure of a wide range of diseases are a serious challenge for modern healthcare. Difficulties in the treatment of cognitive disorders are determined by many factors, including the age of patients, comorbidity, forced polypragmasia and the adequacy of the dosage of drugs that restore cognitive activity. The experts discussed information about the therapeutic potential of the drug Cerebrolysin in the treatment of cognitive disorders of various origins, stated significant experience of its effective and safe use in many clinical studies in mild and moderate forms of dementia. At the same time, there was a lack of consistent and systematic data on the dosage regimen, frequency, and duration of use of the drug in different forms of cognitive impairment and the degree of their severity. The aim of the international council of experts was to determine the optimal dosage regimens of the drug Cerebrolysin in patients with various etiologies and severity of cognitive impairment. The result of the work was the approval of a unified scheme for the use of the drug Cerebrolysin, considering the severity of the disease and its duration.

A retrospective study of Cerebrolysin in patients with moderate to severe traumatic brain injury: Cognitive and functional outcomes.

Claudio Soto, Pablo Salinas, Daniel Muñoz +4 more

In this retrospective study, we aimed to evaluate the effects of the neurotrophic compound Cerebrolysin on executive, cognitive, and functional performance in patients with traumatic brain injury (TBI) with a highly severe disability level. A total of 44 patients were included in the study, with 33 patients in the control group and 11 patients in the interventional group who received intravenous infusions of 30 mL Cerebrolysin. Both groups received standard rehabilitation therapy following the rehabilitation protocol for patients with TBI at Hospital Clínico Mutual de Seguridad. Functional and cognitive scales were evaluated at baseline, at four months, and at the endpoint of the intervention therapy at seven months (on average). The results revealed a significant improvement in the Cerebrolysin-treated group compared to the control group. Specifically, patients who received Cerebrolysin showed a moderate residual disability and a significant reduction in the need for care. Concerning the promising results and considering the limitations of the retrospective study design, we suggest that randomized controlled studies be initiated to corroborate the positive findings for Cerebrolysin in patients with moderate to severe brain trauma.

Nanowired delivery of antibodies to tau and neuronal nitric oxide synthase together with cerebrolysin attenuates traumatic brain injury induced exacerbation of brain pathology in Parkinson's disease.

Asya Ozkizilcik, Aruna Sharma, Lianyuan Feng +7 more

Concussive head injury (CHI) is one of the major risk factors for developing Parkinson's disease in later life of military personnel affecting lifetime functional and cognitive disturbances. Till date no suitable therapies are available to attenuate CHI or PD induced brain pathology. Thus, further exploration of novel therapeutic agents are highly warranted using nanomedicine in enhancing the quality of life of veterans or service members of US military. Since PD or CHI induces oxidative stress and perturbs neurotrophic factors regulation associated with phosphorylated tau (p-tau) deposition, a possibility exists that nanodelivery of agents that could enhance neurotrophic factors balance and attenuate oxidative stress could be neuroprotective in nature. In this review, nanowired delivery of cerebrolysin-a balanced composition of several neurotrophic factors and active peptide fragments together with monoclonal antibodies to neuronal nitric oxide synthase (nNOS) with p-tau antibodies was examined in PD following CHI in model experiments. Our results suggest that combined administration of nanowired antibodies to nNOS and p-tau together with cerebrolysin significantly attenuated CHI induced exacerbation of PD brain pathology. This combined treatment also has beneficial effects in CHI or PD alone, not reported earlier.