Current neuroprotective agents in stroke.

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.

The administration of Cerebrolysin elicits neuroprotective and neurorepair effects in an animal model of type 1 diabetes mellitus.

Diabetes mellitus (DM) is a metabolic disorder impacting cerebral function. The administration of Streptozotocin (STZ) is a well-known animal model of insulinopenic type 1 DM in rats. STZ-induced DM results in a myriad of alteration in the periphery and central nervous system (CNS). Cerebrolysin (CBL) is a neuropeptide preparation that promotes synaptic and neuronal plasticity in various animal models. In all cases, CBL was administered when the model was established. This research aims to investigate the neuroprotective and neurorepair effect of CBL on the cytoarchitecture of neurons and spine density in pyramidal neurons of the prefrontal (PFC) and the CA1 region of the dorsal hippocampus, as well as spheroidal neurons of the dentate gyrus (DG), in STZ-induced DM. In the first experimental condition, STZ and CBL are administered at the same time to evaluate the potential preventive effect of CBL. In the second experimental condition, CBL was administered two months after establishing the DM model to measure the potential neurorepair effect of CBL. STZ-induced hyperglycemia remained unaltered by the administration of CBL in both experimental conditions. In the first experimental condition, CBL treatment preserved the neuronal morphology in PFC layer 3, PFC layer 5 and the DG of the hippocampus, while also maintaining spine density in the PFC-3, DG and CA1 hippocampus. Furthermore, CBL induced neurorepair in neurons within the PFC-3, PFC-5 and CA1 regions of the hippocampus, along with an increase in spine density in the PFC-3, DG and CA1 hippocampus. These findings suggest that CBL´s effects on neuroplasticity could be observed before or after the damage was evident.

[Cognitive impairment in post-traumatic stress disorder]. / Kognitivnye narusheniya pri posttravmaticheskom stressovom rasstroistve.

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.

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.

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.

Nature's Toolbox for Alzheimer's Disease: A Review on the Potential of Natural Products as Alzheimer's Disease Drugs.

Numerous clinical trials involving natural products have been conducted to observe cognitive performances and biomarkers in Alzheimer's Disease (AD) patients. However, to date, no natural-based drugs have been approved by the FDA as treatments for AD. In this review, natural product-based compounds that were tested in clinical trials from 2011 to 2023, registered at www.clinicaltrials.gov were reviewed. Thirteen compounds, encompassing 7 different mechanisms of action were covered. Several observations were deduced, which are: i) several compounds showed cognitive improvement, but these improvements may not extend to AD, ii) compounds that are endogenous to the human body showed better outcomes, and iii) Docosahexaenoic acid (DHA) and cerebrolysin had the most potential as AD drugs among the 13 compounds. Based on the current findings, natural products may be more suitable as a supplement than AD drugs in most cases. However, the studies covered here were conducted in a relatively short amount of time, where compounds acting on AD pathways may take time to show any effect. Given the diverse pathways that these natural products are involved in, they may potentially produce synergistic effects that would be beneficial in treating AD. Additionally, natural products benefit from both physicochemical properties being in more favorable ranges and active transport playing a more significant role than it does for synthetic compounds.

Radioprotective effect of Cerebrolysin in the Rat's Brain Tissues.

AIM: The aim of this study is to evaluate radioprotective effects of Cerebrolysin (CBL) in rats' brain tissues after local irradiation. BACKGROUND: CBL has demonstrated antioxidant, anti-inflammatory, and tissue repair properties. In this study, the radioprotective effects of CBL in the brain tissues of rats after Irradiation (IR) (50 mg/ kg) were evaluated. OBJECTIVE: The levels of different oxidative stress markers, including malondialdehyde (MDA), nitric oxide (NO), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) were examined after treatment with radiation and CBL. METHODS: First, 20 male adult Wistar rats weighing 180-200 g were used. The animals were exposed to a single fraction of 15Gy using a linear accelerator unit at a dose rate of 200 cGy/mine. In this study, to check the amount of oxidative stress following the IR, the level of four markers MDA, NO, GPx, CAT, and SOD were examined and measured using the spectrophotometric method and purchased kits. RESULTS: The results showed that compared to the IR group, the administration of CBL increases the levels of GPX and SOD significantly (p < 0.05). CONCLUSION: Our finding suggests that CBL has radioprotective effects on the brain by enhancing antioxidant defense mechanisms.

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.

OBJECTIVES: 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. METHODS: Neuro-2A cells were exposed to tert-butyl hydroperoxide, a consistent in vitro model of neuronal damage caused by oxidative stress. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, acridine orange/ethidium bromide (AO-EtBr) staining, and phase-view examinations were utilized to evaluate cell survival and cytotoxicity. Real-time reverse transcription-polymerase chain reaction (RT-PCR)-based gene expression studies were conducted. KEY FINDING: Observations revealed that these two medications had modest but considerable neuroprotective effects. While the majority of the genes' expressions remained unchanged, cerebrolysin upregulated Neuregulin 1, and both upregulated brain-derived neurotrophic factor (BDNF) expression. CONCLUSION: The findings of the current study may be the first to suggest that citicoline and cerebrolysin may increase host cells' defense mechanisms (secretion neurotrophic factors) rather than carrying nutrients for cell survival. Because of its simplicity, the current study can readily be repeated to learn more about these two disputed medications for treating ischemic stroke.

[Cerebrolysin as an early add-on to reperfusion therapy: heterogeneous treatment effect analysis in ischemic stroke patients with varying risk of hemorrhagic transformation]. / Effektivnost' rannego primeneniya Tserebrolizina pri reperfuzionnoi terapii: analiz geterogennykh effektov vozdeistviya u bol'nykh s ishemicheskim insul'tom pri razlichnom riske gemorragicheskoi transformatsii.

OBJECTIVE: The study goal was the assessment of heterogeneous treatment effects of Cerebrolysin as an early add-on to reperfusion therapy in stroke patients with varying risk of hemorrhagic transformation (HT). MATERIAL AND METHODS: It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744). Patients with middle cerebral artery infarction (n=238) were stratified by HT risk with the HTI score. The study outcomes were symptomatic and any HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90. Favorable outcome was defined as an mRS score of ≤2. Heterogeneous treatment effect analysis was performed using techniques of meta-analysis and the matching-smoothing method. RESULTS: Heterogeneity of Cerebrolysin treatment effects was moderate (I2=36.98-69.3%, H2=1.59-3.26) and mild (I2=18.33-32.39%, H2=1.22-1.48) for symptomatic and any HT, respectively. A positive impact of the Cerebrolysin treatment on HT and functional outcome was observed in patients with moderate (HTI=1) and high (HTI≥2) HT risk. However, the effect was neutral in those with low risk (HTI=0). In high HT risk patients, there was a steady decline in the rate of symptomatic (HTI=0 vs. HTI≥2: by 3.8%, p=0.120 vs. 14.3%, p<0.001) and any HT (HTI=0 vs. HTI≥2: by 0.6%, p=0.864 vs. 19.5%, p<0.001). Likewise, Cerebrolysin treatment resulted in an overall decrease in the mRS scores (HTI=0 vs. HTI≥2: by 2.1%, p=0.893 vs. 63%, p<0.001) with a reciprocal increase of the fraction with favorable outcome (HTI=0 vs. HTI≥2: by 2% p=0.634 vs. 19.2%, p<0.001). CONCLUSION: Clinically meaningful heterogeneity of Cerebrolysin treatment effects on HT and functional outcome was established in stroke patients. The Cerebrolysin positive impact was significant in those whose estimated on-admission HT risk was either moderate or high.

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

Background: 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. New method: Nerve growth factor is known to induce Neurofilament-L (NF-L) expression in a rat pheochromocytoma cell line (PC12 cells) during early neuronal differentiation. We generated and characterized an enhanced green fluorescent protein (EGFP)-NF-L reporter PC12 cell line for the development of a cell-based assay (designated Neurofilament-L Bioassay) that allows straightforward quantification of early neuronal differentiation based on NF-L expression. Results: Using Cerebrolysin® as a role model for a pharmacological compound that stimulates neurotrophic activity in the central nervous system, the Neurofilament-L Bioassay was proved to be a robust, specific, and reproducible method. Comparison with existing methods: It was already shown that NF-L expression correlates with neurite outgrowth in PC12 cells. Currently, quantification of neurite outgrowth is the most commonly used method to evaluate neuronal differentiation in PC12 cells, an approach that is time-consuming and of high variability. Conclusions: This work describes the development of an EGFP-NF-L reporter PC12 cell-based assay as a robust and reproducible tool for "high throughput" compound screening for neurotrophic activity.

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

RATIONALE: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The Effects of Neuromonitoring and Cerebrolysin Administration on Outcomes in Patients with Traumatic Brain Injury-An Interventional Pilot Study.

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.

[Traumatic brain injury as risk factor of Alzheimer's disease and possibilities of pathogenetic therapy]. / Cherepno-mozgovaya travma kak faktor riska bolezni Al'tsgeimera i vozmozhnosti patogeneticheskoi terapii.

The article examines the potential role of brain mechanical damage as a trigger for the development of neurodegenerative changes. Attention is paid to dysfunction of the neurovascular unit, and disruption of the functional and compensatory capabilities of blood flow. The importance of microhemorrhages that occur in the acute period of injury and the formation of first focal and then diffuse neuroinflammation is emphasized. The importance of mitochondrial dysfunction was separately determined as a significant factor in increasing the risk of developing Alzheimer's disease (AD) in patients after traumatic brain injury (TBI). In TBI, there is a decrease in the expression of tight junction (TC) proteins of endothelial cells, such as occludin, claudin, JP, which leads to increased permeability of the blood-brain barrier. TBI, provoking endothelial dysfunction, contributes to the development of metabolic disorders of ß-amyloid and tau protein, which in turn leads to worsening vascular damage, resulting in a vicious circle that can ultimately lead to the development of AD and dementia. Age-related changes in cerebral arteries, which impair perivascular transport of interstitial fluid, are currently considered as an important part of the «amyloid cascade¼, especially against the background of genetically mediated disorders of glial membranes associated with defective aquaporin-4 (encoded by the APOE4). Studies in animal models of TBI have revealed an increase in tau protein immunoreactivity and its phosphorylation, which correlates with the severity of injury. A comprehensive analysis of research results shows that the cascade of reactions triggered by TBI includes all the main elements of the pathogenesis of AD: disorders of energy metabolism, microcirculation and clearance of cerebral metabolic products. This leads to a disruption in the metabolism of amyloid protein and its accumulation in brain tissue with the subsequent development of tauopathy. Cerebrolysin, by modulating the permeability of the blood-brain barrier, blocks the development of neuroinflammation, reduces the accumulation of pathological forms of proteins and may be slow down the progression of neurodegeneration.

Environmental enrichment and cerebrolysin improve motor and cognitive performance in a rat model of stroke, in conjunction with an increase in hippocampal AMPA but not NMDA receptor subunits.

Stroke is a pathology related to the vascular system in the brain and it is one of the main causes of disability, representing a burden on public health. This lesion provokes a disorganization of sensory-motor and cognitive systems, the latter associated with hippocampal activity, a structure in which α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA N-methyl-D-aspartate (NMDA) receptors are important for the integration of information. Several molecules have been studied for their capacity to enhance recovery from a stroke, including cerebrolysin that could potentially be reinforced by environmental enrichment. Here, stroke was induced in 40 male rats and 24 h later, they were administered cerebrolysin (2.5 ml/kg), put in an environmentally enriched arena or given both treatments, for 10 days. Subsequently, motor functioning was assessed with the Bederson test and the cognitive domain was assessed through novel object recognition. Hematoxylin/eosin staining was then used to assess the infarct size, and AMPA-GRIA1 and NMDA-R1 subunits in the hippocampus were measured by ELISA. In motor and cognitive performance, the administration of cerebrolysin and environmental enrichment enhanced recovery. Moreover, the infarct size decreased in all the groups that received a treatment, but an increase occurred in AMPA-GRIA1 only in experimental group regarding to control group, while NMDA-R1 had no differences. These results suggest that cerebrolysin and environmental enrichment could act in synergy to recover after a stroke, leading to a smaller infarct area and the presence of more AMPA-GRIA1 subunits in the hippocampus of experimental group. These data encourage further studies in which neurorehabilitation approaches can be combined with cerebrolysin administration to treat the motor and cognitive symptoms of stroke.

Treatment with Cerebrolysin Prolongs Lifespan in a Mouse Model of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy.

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.

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

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.

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.

BACKGROUND: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: NCT04830943.

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

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.

Stress induced exacerbation of Alzheimer's disease brain pathology is thwarted by co-administration of nanowired cerebrolysin and monoclonal amyloid beta peptide antibodies with serotonin 5-HT6 receptor antagonist SB-399885.

Alzheimer's disease is one of the devastating neurodegenerative diseases affecting mankind worldwide with advancing age mainly above 65 years and above causing great misery of life. About more than 7 millions are affected with Alzheimer's disease in America in 2023 resulting in huge burden on health care system and care givers and support for the family. However, no suitable therapeutic measures are available at the moment to enhance quality of life to these patients. Development of Alzheimer's disease may reflect the stress burden of whole life inculcating the disease processes of these neurodegenerative disorders of the central nervous system. Thus, new strategies using nanodelivery of suitable drug therapy including antibodies are needed in exploring neuroprotection in Alzheimer's disease brain pathology. In this chapter role of stress in exacerbating Alzheimer's disease brain pathology is explored and treatment strategies are examined using nanotechnology based on our own investigation. Our observations clearly show that restraint stress significantly exacerbate Alzheimer's disease brain pathology and nanodelivery of a multimodal drug cerebrolysin together with monoclonal antibodies (mAb) to amyloid beta peptide (AßP) together with a serotonin 5-HT6 receptor antagonist SB399885 significantly thwarted Alzheimer's disease brain pathology exacerbated by restraint stress, not reported earlier. The possible mechanisms and future clinical significance is discussed.

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.

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.