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Background: Subarachnoid hemorrhage (SAH) is associated with high mortality and a high level of disability. Progress in surgical and endovascular techniques has lowered the mortality rate in patients with SAH. However, many patients are left with neurological impairment. Objectives: In our study we wanted to examine the impact of Cerebrolysin on treatment results in patients with SAH diagnosis. Methods: The data of 47 patients, divided into Cerebrolysin (26) and non-Cerebrolysin (21) group were included. We examined the correlation between Cerebrolysin administration and additional Amantadine treatment or neuromonitoring, craniectomy, and endovascular treatment and its impact on the Glasgow Outcome Scale (GOS) score, length of stay (LOS), and mortality. Results: Our study shows that Cerebrolysin improves the mortality rate in combination with neuromonitoring in a group of patients with severe SAH. It does not affect the raw values of GOS or LOS in patients with SAH. Conclusions: Further studies with larger patient groups are needed to investigate the role of Cerebrolysin as an additional treatment in SAH. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Alcoholism presents a significant health concern with notable socioeconomic implications. Alcohol withdrawal syndrome (AWS) can manifest when individuals cease or drastically reduce their alcohol consumption after prolonged use. Non-alcoholic fatty liver disease (NAFLD) is characterized by substantial lipid accumulation in the liver cells of individuals with no history of alcohol consumption. There is evidence suggesting an association between cognitive impairment and both conditions. This study aimed to evaluate cognitive impairment in patients with NAFLD and AWS using the Mini-Mental State Examination (MMSE). This study involved 120 patients admitted to two hospitals in Craiova, Romania. Results indicated that patients with NAFLD did not exhibit cognitive impairment as measured by MMSE (Mean = 29.27, SD = 0.785). Conversely, patients with AWS showed more pronounced cognitive dysfunction, with a mean MMSE score at admission of 16.60 ± 4.097 and 24.60 ± 2.832 after 2 weeks under treatment with Vitamins B1 and B6 and Cerebrolysin. Additionally, our findings suggested that cognitive dysfunction among alcohol consumers was correlated with the severity of clinical symptoms, as demonstrated by the severity of tremors in our study. The two-week period under treatment and alcohol withdrawal was insufficient for cognitive function to return to normal levels. Observational studies on longer periods of time are advised.

• pMCAO induces cognitive symptoms that are highly disabling. • Combined cerebrolysin and nicotinamide reduced infarct and cognitive symptoms. • Cerebrolysin and nicotinamide combination promoted dendritic growth in hippocampal neurons. • BDNF levels increased after cerebrolysin and nicotinamide acute combined administration. 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. [ABSTRACT FROM AUTHOR]

Alcoholism presents a significant health concern with notable socioeconomic implications. Alcohol withdrawal syndrome (AWS) can manifest when individuals cease or drastically reduce their alcohol consumption after prolonged use. Non-alcoholic fatty liver disease (NAFLD) is characterized by substantial lipid accumulation in the liver cells of individuals with no history of alcohol consumption. There is evidence suggesting an association between cognitive impairment and both conditions. This study aimed to evaluate cognitive impairment in patients with NAFLD and AWS using the Mini-Mental State Examination (MMSE). This study involved 120 patients admitted to two hospitals in Craiova, Romania. Results indicated that patients with NAFLD did not exhibit cognitive impairment as measured by MMSE (Mean = 29.27, SD = 0.785). Conversely, patients with AWS showed more pronounced cognitive dysfunction, with a mean MMSE score at admission of 16.60 ± 4.097 and 24.60 ± 2.832 after 2 weeks under treatment with Vitamins B1 and B6 and Cerebrolysin. Additionally, our findings suggested that cognitive dysfunction among alcohol consumers was correlated with the severity of clinical symptoms, as demonstrated by the severity of tremors in our study. The two-week period under treatment and alcohol withdrawal was insufficient for cognitive function to return to normal levels. Observational studies on longer periods of time are advised. [ABSTRACT FROM AUTHOR]

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. The present study aims to investigate the effect of lithium augmentation with cerebrolysin on the neurochemical, behavioral and histopathological alterations induced in the reserpine model of depression. The animals were divided into control and reserpine-induced model of depression. The model animals were further divided into rat model of depression, rat model treated with lithium, rat model treated with cerebrolysin and rat model treated with a combination of lithium and cerebrolysin. Treatment with lithium, cerebrolysin, or their combination alleviated most of the changes in behavior, oxidative stress parameters, acetylcholinesterase and monoamines in the cortex and hippocampus of the reserpine-induced model of depression. It also improved the alterations in brain-derived neurotrophic factor (BDNF) and histopathology induced by reserpine. The augmentation of lithium with cerebrolysin showed a clear beneficial effect in the present model of depression suggesting the use of cerebrolysin as an adjuvant in antidepressant treatment. [ABSTRACT FROM AUTHOR]

What is expected from neuroprotection is to inhibit neuronal death and halt or decelerate the neuronal loss to lower the mortality rates, decrease disability, and improve the quality of life following an acute ischemic stroke. Several agents were described as neuroprotective up to date; however, there is still debate which to use in the neurorehabilitation of stroke patients, in terms of both efficacy and also safety. In this review, we discuss the agents, citicoline, cerebrolysin and MLC901 (NeuroAiD II), the three agents which have started to be used frequently in neurorehabilitation clinics recently in the light of the current literature. [ABSTRACT FROM AUTHOR]

Background: Subarachnoid hemorrhage (SAH) is associated with high mortality and a high level of disability. Progress in surgical and endovascular techniques has lowered the mortality rate in patients with SAH. However, many patients are left with neurological impairment. Objectives: In our study we wanted to examine the impact of Cerebrolysin on treatment results in patients with SAH diagnosis. Methods: The data of 47 patients, divided into Cerebrolysin (26) and non-Cerebrolysin (21) group were included. We examined the correlation between Cerebrolysin administration and additional Amantadine treatment or neuromonitoring, craniectomy, and endovascular treatment and its impact on the Glasgow Outcome Scale (GOS) score, length of stay (LOS), and mortality. Results: Our study shows that Cerebrolysin improves the mortality rate in combination with neuromonitoring in a group of patients with severe SAH. It does not affect the raw values of GOS or LOS in patients with SAH. Conclusions: Further studies with larger patient groups are needed to investigate the role of Cerebrolysin as an additional treatment in SAH.

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. [ABSTRACT FROM AUTHOR]

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare familial neurological disorder caused by mutations in the NOTCH3 gene and characterized by migraine attacks, depressive episodes, lacunar strokes, dementia, and premature death. Since there is no therapy for CADASIL the authors investigate whether the multi‐modal neuropeptide drug Cerebrolysin may improve outcome in a murine CADASIL model. Twelve‐month‐old NOTCH3R169C mutant mice (n=176) are treated for nine weeks with Cerebrolysin or Vehicle and histopathological and functional outcomes are evaluated within the subsequent ten months. Cerebrolysin treatment improves spatial memory and overall health, reduces epigenetic aging, and prolongs lifespan, however, CADASIL‐specific white matter vacuolization is not affected. On the molecular level Cerebrolysin treatment increases expression of Calcitonin Gene‐Related Peptide (CGRP) and Silent Information Regulator Two (Sir2)‐like protein 6 (SIRT6), decreases expression of Insulin‐like Growth Factor 1 (IGF‐1), and normalizes the expression of neurovascular laminin. In summary, Cerebrolysin fosters longevity and healthy aging without specifically affecting CADASIL pathology. Hence, Cerebrolysin may serve a therapeutic option for CADASIL and other disorders characterized by accelerated aging. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Traumatic brain injury (TBI) is one of the most common causes of death and an important burden to the worldwide healthcare system and society. There is a lack of guidelines for types of monitoring or neuroprotective therapy. The aim of this pilot study was to assess its feasibility and, furthermore, to evaluate the impact of Cerebrolysin on the following clinical outcomes: length of stay, Glasgow Outcome Scale (GOS) and mortality. Methods: A cohort of 56 patients was included in this non-randomised, real-time, pre–post-interventional study. The patients were assessed with the Glasgow Coma Scale (GCS) and divided into two groups: severe (GCS < 8) and non-severe (GCS > 8). After the radiological examination (CT scan), the patients were qualified for an immediate neurosurgical procedure if needed. The patients were admitted to the intensive care unit, where a standardised protocol for TBI treatment was implemented. Additional neuromonitoring was applied. Results: There were 56 patients (19 females; 33.9%), of which 41 were considered severe cases; the patients were allocated to the Cerebrolysin (n = 25) or control groups (n = 31). In a generalised linear model (GLM) approach, the use of Cerebrolysin was associated with a decrease in the probability of death in non-severe patients (by 0.333 (standard error (SE) = 0.157, p = 0.034)) but not in severe patients (estimate (Est.) = −0.115, SE = 0.127, p = 0.364). Patients who received Cerebrolysin and who were neuromonitored had favourable outcomes and better survival rates. Conclusions: A multimodal treatment approach with monitoring and Cerebrolysin may have a beneficial effect on patients with less severe TBIs; however, the present study has multiple limitations, and further research is needed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Worldwide, cerebral vascular disease is the second cause of death and the main cause of disability. It is estimated that, from the age of 25, 1 in every 4 people in the world will suffer a cerebrovascular event in their lifetime. Cerebrolysin has neuroprotective and neurorepair properties. This paper communicates the findings of different studies of the role of cardiolysin in neuroprotection. [ABSTRACT FROM AUTHOR]

Aim: Stroke is the second most common cause of mortality and disability worldwide with ischemic strokes being the predominant type. The advent of neuroprotectants brought hope of improved outcomes and quality of life, but current guidelines, despite numerous trials, have no strong recommendation advising their use. This meta-analysis aims to evaluate the degree of effect and safety of the neuroprotectants cytidine-5’-diphosphocholine (CDP-choline), cerebrolysin, edaravone, and MLC601, in the recovery of patients with cerebral infarcts. Methods: An extensive literature search, through the databases of PubMed, PMC, Cochrane, and Ovid, was done with the keywords “CDP-choline”, “cerebrolysin”, “MLC601”, and “edaravone” each combined with the term “acute ischemic stroke”. Eligible studies included randomized controlled trials of these neuroprotectants administered to patients with acute ischemic strokes. A total of 2,025 studies were found, and after the application of screening criteria, 24 studies were eligible for analysis. Results: The analysis showed that the functional outcome of patients with acute ischemic strokes improved significantly when receiving neuroprotectants versus placebo supported by an odds ratio = 0.29 (0.09–0.50) with a confidence interval of 95%. The P-values are 0.0022 for the one-tailed test, and 0.0030 for the two-tailed test which express the significant improvement of functional outcomes in patients with acute ischemic strokes taking neuroprotectants. Conclusions: This study thus supports the use of neuroprotectants in patients with acute ischemic strokes to improve long-term functional outcomes and ultimately quality of life.

Abstract Background Spinal cord injury (SCI) is widely considered the most disastrous medical condition. With no available treatment to date, SCI continues to cause disabilities to the patients and affect their own and their caregivers' quality of life. Cerebrolysin (CBL) is a neuropeptide preparation derived from purified brain proteins with suggested neuroprotective and neurotrophic properties. CBL showed earlier the ability to target multiple pathways that helped in the improvement of the recovery following different groups of neurological diseases and injuries, including ischemic stroke, traumatic brain injuries, and even neurodegenerative diseases. In the current study, the neuroprotective effect of CBL following a SCI is called into question using a rat model of spinal cord cervical hemi-section validated earlier by our lab and others. Using 32 rats divided into four groups randomly, CBL treatment was implemented for either 7 or 21 days duration, following the cervical spinal cord hemi-section. Results Following the CBL treatment, rats with cervical cord hemi-section showed functional improvement of diaphragmatic muscle as recorded by electromyography (EMG). In addition, the histopathological assessment of the spinal cord showed improved neuronal viability and reduced astrogliosis at the site of the injury compared to the non-treated group. 21-day treatment showed significant improvement when compared to the shorter 7-day regimen. Conclusion Our data suggest that CBL is capable of protecting and regenerating anterior horn motor neurons with functional recovery of diaphragmatic muscle functions in rats, suggesting the potential use of CBL for future regenerative and neuroprotective therapy following SCI.

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.

Amyotrophic lateral sclerosis (ALS) is a devastating and progressive neurodegenerative disease with limited treatment options available. Cerebrolysin is a drug candidate for the treatment of ALS because of its neuroprotective and neuroregenerative effects. We initiated a pilot clinical study of a combination of Cerebrolysin and riluzole to assess the therapeutic benefit of Cerebrolysin as an add-on treatment on clinical signs and symptoms in outpatients with ALS. Twenty patients with a clinically definitive diagnosis of ALS were enrolled and randomly assigned in a 1:1 ratio to receive Cerebrolysin or placebo. All patients received 50 mg of riluzole PO twice daily as a standard treatment. Patients in the Cerebrolysin group received intravenous injections of 10 mL of Cerebrolysin once daily, five days a week for the first month and three days a week for the next two months. Analysis of the ALS Functional Rating Scale - revised at Month 1 (primary outcome measure), showed a significant treatment effect in favor of Cerebrolysin with a 2.3-point improvement from baseline to Month 1 compared to a 0.9-point decrease in patients on placebo (P=0.005). The effect was maintained over the three-month study period, and the beneficial effect of Cerebrolysin over placebo was also evident in the secondary outcome measures. The safety analysis showed that the combination of riluzole and Cerebrolyisn was well tolerated. Our results demonstrate for the first time a significant clinical effect of Cerebrolysin in improving functional outcomes in patients with ALS and suggest that Cerebrolysin has potential as a novel therapeutic option for ALS. [ABSTRACT FROM AUTHOR]

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. This was a prospective randomized trial. It included 250 patients (male = 93, female = 157; age: 31.3 ± 8.9 years). Patients were randomized into group 1 (n = 150): received cerebrolysin [5 ml/d (IM), 5d/week] and practiced olfactory and gustatory trainings, and group 2 (n = 100): practiced olfactory and gustatory trainings only, for ≥ 8–24 weeks. Measures of outcomes were: a clinical questionnaire; sniffin' odor, taste and flavor identification tests; and global rating scales for smell and taste. The duration of disorders was 11.7 ± 3.7mo (range: 6-24mo). The majority (n = 167; 66.8%) developed parosmia within months (3.6 ± 2.7mo) after anosmia. Objective testing showed anosmia in all and taste, flavor, and trigeminal sensory losses in 18% (n = 45). Analyses for secondary outcome were done on 202 patients (group 1 = 130; group 2 = 72). Recovery was complete in 61.5% (n = 80) with cerebrolysin therapy and partial in 17% (n = 22). There was no recovery with trainings only. There were no predictors for recovery. Cerebrolysin had fast, promising, and constant effect, with cure rate of > 60%. This might be due to its ability to initiate and enhance neuronal regeneration and reorganization of sensory epithelia. NCT04830943. [ABSTRACT FROM AUTHOR]

Background: Spinal cord injury (SCI) is widely considered the most disastrous medical condition. With no available treatment to date, SCI continues to cause disabilities to the patients and affect their own and their caregivers' quality of life. Cerebrolysin (CBL) is a neuropeptide preparation derived from purified brain proteins with suggested neuroprotective and neurotrophic properties. CBL showed earlier the ability to target multiple pathways that helped in the improvement of the recovery following different groups of neurological diseases and injuries, including ischemic stroke, traumatic brain injuries, and even neurodegenerative diseases. In the current study, the neuroprotective effect of CBL following a SCI is called into question using a rat model of spinal cord cervical hemi-section validated earlier by our lab and others. Using 32 rats divided into four groups randomly, CBL treatment was implemented for either 7 or 21 days duration, following the cervical spinal cord hemi-section. Results: Following the CBL treatment, rats with cervical cord hemi-section showed functional improvement of diaphragmatic muscle as recorded by electromyography (EMG). In addition, the histopathological assessment of the spinal cord showed improved neuronal viability and reduced astrogliosis at the site of the injury compared to the non-treated group. 21-day treatment showed significant improvement when compared to the shorter 7-day regimen. Conclusion: Our data suggest that CBL is capable of protecting and regenerating anterior horn motor neurons with functional recovery of diaphragmatic muscle functions in rats, suggesting the potential use of CBL for future regenerative and neuroprotective therapy following SCI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Recent preclinical and clinical reports suggest that cerebrolysin shows neuroprotective properties similar to endogenous neurotrophic factors in neurodegenerative disorders including ischemic stroke. However, little is known about its underlying antiexcitotoxic action. Adult male Wistar rats were intraperitoneally treated with cerebrolysin (0.15 or 0.30 mg/kg) or vehicle at 3, 6 and 12 h after ischemic reperfusion and were assessed 24 h after reperfusion in ischemic rats. We added cerebrolysin (2.5 or 5 mg/ml) or vehicle in primary cortical culture cells at 3, 6 and 12 h of post-glutamate exposure and performed cell viability assays at 24 h. Our in-vivo and in-vitro findings showed that cerebrolysin substantially reduced neuronal cell death in delayed hours of post ischemic- and glutamate-insult conditions respectively. Further, we have assessed the influence of NR-2 A/-2B receptor antagonism on neuroprotective action of cerebrolysin at 6 h in in-vivo as well as in-vitro conditions. Neuroprotective effect of cerebrolysin at 6 h of reperfusion was enhanced by pretreatment of NR2B antagonist RO25-6981.We found that cerebrolysin restrained upregulation of extrasynaptic NR2B responsible for triggering apoptotic pathways. Cerebrolysin reduced expression of important cell death proteins such as, JNK, PTEN, Calpain and Caspase-3 components. Importantly, we also found that cerebrolysin reduced SREBP1 expression, which gets activated only after 6 h of ischemia. These results demonstrate that cerebrolysin reduces excitotoxicity and protect neuronal cells in delayed hours of ischemic reperfusion injuries by decreasing cell death proteins. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Neurotrophic factors (NTFs) are involved in the pathophysiology of neurological disorders such as dementia, stroke and traumatic brain injury (TBI), and constitute molecular targets of high interest for the therapy of these pathologies. In this review we provide an overview of current knowledge of the definition, discovery and mode of action of five NTFs, nerve growth factor, insulin‐like growth factor 1, brain derived NTF, vascular endothelial growth factor and tumor necrosis factor alpha; as well as on their contribution to brain pathology and potential therapeutic use in dementia, stroke and TBI. Within the concept of NTFs in the treatment of these pathologies, we also review the neuropeptide preparation Cerebrolysin, which has been shown to resemble the activities of NTFs and to modulate the expression level of endogenous NTFs. Cerebrolysin has demonstrated beneficial treatment capabilities in vitro and in clinical studies, which are discussed within the context of the biochemistry of NTFs. The review focuses on the interactions of different NTFs, rather than addressing a single NTF, by outlining their signaling network and by reviewing their effect on clinical outcome in prevalent brain pathologies. The effects of the interactions of these NTFs and Cerebrolysin on neuroplasticity, neurogenesis, angiogenesis and inflammation, and their relevance for the treatment of dementia, stroke and TBI are summarized. [ABSTRACT FROM AUTHOR]

• Fucoidan, Cerebrolysin combo effectively reduced the infarct size in the MCAo brain. • Novel drug combo downregulated the proinflammatory markers in the MCAo rats. • Combination treatment preserved the sensorimotor function in the rats after MCAo. Cerebral ischemic reperfusion injury could emanate a cascade of events ensuing in neural death and severe neurobehavioural deficits. The currently available interventions have failed to target the multimodal, interlinked mechanisms that operate cerebral ischemia-induced damage and functional loss. So an integrative intervention has become a mandate to overcome the deleterious mechanisms involved in cerebral ischemic pathophysiology. In this study, adult male Sprague dawley rats were exposed to 2 hours of right middle cerebral artery occlusion (rMCAo) followed by reperfusion, and the intervention group received Fucoidan alone at a dose of 50 mg/kg, i.p (intraperitoneal), Cerebrolysin alone at a dose of 2.5 mg/kg body weight and the combination of both. The sham rats were exposed to surgical procedures, except for the rMCAo. The assessments of the groups were made 24 h after the rMCAo. The stand-alone treatment with Fucoidan, Cerebrolysin has shown a better outcome in the neurobehavioral and, histopathological assessments and the combination has made a significant reduction in the neurological deficits and the infarct volume when compared to the standalone groups. The BBB integrity was well preserved in the combination group when compared with the lesion and standalone groups. Moreover, the combined intervention reduced the level of pro-inflammatory cytokines TNFα, NFkB, IL1α, IL1-β, IL-6, CD68, COX-2, and mRNA expression of inflammatory genes IL1α, IL1-β, IL-6, IBA-1, and COX-2 effectively. In conclusion, the present study suggests that rMCAo induced neuroinflammation and neurobehavioural alterations were attenuated by intervention with a combination of Fucoidan and cerebrolysin; Further, Fucoidan and Cerebrolysin combination improved the ischemic tolerance level by promoting the proteins and genes that regulate the inflammatory cytokines and in aiding better recovery after ischemic reperfusion injury. [ABSTRACT FROM AUTHOR]

Forebrain ischemia-reperfusion (IR) injury causes neurological impairments due to decreased cerebral autoregulation, hypoperfusion, and edema in the hours to days following the restoration of spontaneous circulation. This study aimed to examine the protective and/or therapeutic effects of cerebrolysin (CBL) in managing forebrain IR injury and any probable underlying mechanisms. To study the contribution of reperfusion to forebrain injury, we developed a transient dual carotid artery ligation (tDCAL/IR) mouse model. Five equal groups of six BLC57 mice were created: Group 1: control group (no surgery was performed); Group 2: sham surgery (surgery was performed without IR); Group 3: tDCAL/IR (surgery with IR via permanently ligating the left CA and temporarily closing the right CA for 30 min, followed by reperfusion for 72 h); Group 4: CBL + tDCAL/IR (CBL was given intravenously at a 60 mg/kg BW dose 30 min before IR); and Group 5: tDCAL/IR + CBL (CBL was administered i.v. at 60 mg/kg BW three hours after IR). At 72 h following IR, the mice were euthanized. CBL administration 3 h after IR improved neurological functional recovery, enhanced anti-inflammatory and antioxidant activities, alleviated apoptotic neuronal death, and inhibited reactive microglial and astrocyte activation, resulting in neuroprotection after IR injury in the tDCAL/IR + CBL mice group as compared to the other groups. Furthermore, CBL reduced the TLRs/NF-kB/cytokines while activating the Keap1/Nrf2/antioxidant signaling pathway. These results indicate that CBL may improve neurologic function in mice following IR. [ABSTRACT FROM AUTHOR]