The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Dafin F Muresanu - One of the best experts on this subject based on the ideXlab platform.

  • diabetes exacerbates brain pathology following a focal blast brain injury new role of a multimodal drug Cerebrolysin and nanomedicine
    Progress in Brain Research, 2020
    Co-Authors: Dafin F Muresanu, Aruna Sharma, Jose Vicente Lafuente, Anca Dana Buzoianu, Seaab Sahib, Ryan Z Tian, Rudy J Castellani, Ala Nozari, Lianyuan Feng, Perove Sjoquist
    Abstract:

    Blast brain injury (bBI) is a combination of several forces of pressure, rotation, penetration of sharp objects and chemical exposure causing laceration, perforation and tissue losses in the brain. The bBI is quite prevalent in military personnel during combat operations. However, no suitable therapeutic strategies are available so far to minimize bBI pathology. Combat stress induces profound cardiovascular and endocrine dysfunction leading to psychosomatic disorders including diabetes mellitus (DM). This is still unclear whether brain pathology in bBI could exacerbate in DM. In present review influence of DM on pathophysiology of bBI is discussed based on our own investigations. In addition, treatment with Cerebrolysin (a multimodal drug comprising neurotrophic factors and active peptide fragments) or H-290/51 (a chain-breaking antioxidant) using nanowired delivery of for superior neuroprotection on brain pathology in bBI in DM is explored. Our observations are the first to show that pathophysiology of bBI is exacerbated in DM and TiO2-nanowired delivery of Cerebrolysin induces profound neuroprotection in bBI in DM, not reported earlier. The clinical significance of our findings with regard to military medicine is discussed.

  • concussive head injury exacerbates neuropathology of sleep deprivation superior neuroprotection by co administration of tio2 nanowired Cerebrolysin alpha melanocyte stimulating hormone and mesenchymal stem cells
    Progress in Brain Research, 2020
    Co-Authors: Aruna Sharma, Dafin F Muresanu, Jose Vicente Lafuente, Anca Dana Buzoianu, Seaab Sahib, Ryan Z Tian, Rudy J Castellani, Ala Nozari, Igor Bryukhovetskiy, Igor Manzhulo
    Abstract:

    Sleep deprivation (SD) is common in military personnel engaged in combat operations leading to brain dysfunction. Military personnel during acute or chronic SD often prone to traumatic brain injury (TBI) indicating the possibility of further exacerbating brain pathology. Several lines of evidence suggest that in both TBI and SD alpha-melanocyte-stimulating hormone (α-MSH) and brain-derived neurotrophic factor (BDNF) levels decreases in plasma and brain. Thus, a possibility exists that exogenous supplement of α-MSH and/or BDNF induces neuroprotection in SD compounded with TBI. In addition, mesenchymal stem cells (MSCs) are very portent in inducing neuroprotection in TBI. We examined the effects of concussive head injury (CHI) in SD on brain pathology. Furthermore, possible neuroprotective effects of α-MSH, MSCs and neurotrophic factors treatment were explored in a rat model of SD and CHI. Rats subjected to 48h SD with CHI exhibited higher leakage of BBB to Evans blue and radioiodine compared to identical SD or CHI alone. Brain pathology was also exacerbated in SD with CHI group as compared to SD or CHI alone together with a significant reduction in α-MSH and BDNF levels in plasma and brain and enhanced level of tumor necrosis factor-alpha (TNF-α). Exogenous administration of α-MSH (250μg/kg) together with MSCs (1×106) and Cerebrolysin (a balanced composition of several neurotrophic factors and active peptide fragments) (5mL/kg) significantly induced neuroprotection in SD with CHI. Interestingly, TiO2 nanowired delivery of α-MSH (100μg), MSCs, and Cerebrolysin (2.5mL/kg) induced enhanced neuroprotection with higher levels of α-MSH and BDNF and decreased the TNF-α in SD with CHI. These observations are the first to show that TiO2 nanowired administration of α-MSH, MSCs and Cerebrolysin induces superior neuroprotection following SD in CHI, not reported earlier. The clinical significance of our findings in light of the current literature is discussed.

  • efficacy and safety of Cerebrolysin in neurorecovery after moderate severe traumatic brain injury results from the captain ii trial
    Neurological Sciences, 2020
    Co-Authors: Dafin F Muresanu, Stefan Ioan Florian, Volker Homberg, Christian Matula, Nicole Von Steinbuchel, Pieter E Vos, Klaus Von Wild, Codruta Birle, Ioana Muresanu, Dana Slavoaca
    Abstract:

    The objective of this trial was to evaluate the efficacy and safety of Cerebrolysin in treating patients after moderate to severe traumatic brain injury (TBI) as an adjunct to standard care protocols. The trial was designed to investigate the clinical effects of Cerebrolysin in the acute (neuroprotective) stage and during early and long-term recovery as part of a neurorestorative strategy. The study was a phase IIIb/IV single-center, prospective, randomized, double-blind, placebo-controlled clinical trial. Eligible patients with a Glasgow Coma Score (GCS) between 7 and 12 received study medication (50 ml of Cerebrolysin or physiological saline solution per day for 10 days, followed by two additional treatment cycles with 10 ml per day for 10 days) in addition to standard care. We tested ensembles of efficacy criteria for 90, 30, and 10 days after TBI with a priori ordered hypotheses using a multivariate, directional test, to reflect the global status of patients after TBI. The study enrolled 142 patients, of which 139 underwent formal analysis (mean age = 47.4, mean admission GCS = 10.4, and mean Baseline Prognostic Risk Score = 2.6). The primary endpoint, a multidimensional ensemble of 13 outcome scales, indicated a “small-to-medium”–sized effect in favor of Cerebrolysin, statistically significant at day 90 (MWcombined = 0.59, 95% CI 0.52 to 0.66, P = 0.0119). Safety and tolerability observations were comparable between treatment groups. Our trial confirms previous beneficial effects of the multimodal, biological agent Cerebrolysin for overall outcome after moderate to severe TBI, as measured by a multidimensional approach. Study findings must be appraised and aggregated in conjunction with existing literature, as to improve the overall level of insight regarding therapeutic options for TBI patients. The widely used pharmacologic intervention may benefit from a large-scale observational study to map its use and to establish comparative effectiveness in real-world clinical settings.

  • nanodelivery of Cerebrolysin reduces pathophysiology of parkinson s disease
    Progress in Brain Research, 2019
    Co-Authors: Asya Ozkizilcik, Dafin F Muresanu, Aruna Sharma, Jose Vicente Lafuente, Herbert Mossler, Ryan Z Tian, Rudy J Castellani, Ala Nozari, Hari Shanker Sharma
    Abstract:

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

  • safety and efficacy of Cerebrolysin in early post stroke recovery a meta analysis of nine randomized clinical trials
    Neurological Sciences, 2018
    Co-Authors: Natan M Bornstein, A B Guekht, Johannes C Vester, Wolfdieter Heiss, Eugene Gusev, Volker Homberg, Volker W Rahlfs, Ovidiu Bajenaru, Bogdan Ovidiu Popescu, Dafin F Muresanu
    Abstract:

    This meta-analysis combines the results of nine ischemic stroke trials, assessing efficacy of Cerebrolysin on global neurological improvement during early post-stroke period. Cerebrolysin is a parenterally administered neuropeptide preparation approved for treatment of stroke. All included studies had a prospective, randomized, double-blind, placebo-controlled design. The patients were treated with 30–50 ml Cerebrolysin once daily for 10–21 days, with treatment initiation within 72 h after onset of ischemic stroke. For five studies, original analysis data were available for meta-analysis (individual patient data analysis); for four studies, aggregate data were used. The combination by meta-analytic procedures was pre-planned and the methods of synthesis were pre-defined under blinded conditions. Search deadline for the present meta-analysis was December 31, 2016. The nonparametric Mann-Whitney (MW) effect size for National Institutes of Health Stroke Scale (NIHSS) on day 30 (or 21), combining the results of nine randomized, controlled trials by means of the robust Wei-Lachin pooling procedure (maximin-efficient robust test), indicated superiority of Cerebrolysin as compared with placebo (MW 0.60, P < 0.0001, N = 1879). The combined number needed to treat for clinically relevant changes in early NIHSS was 7.7 (95% CI 5.2 to 15.0). The additional full-scale ordinal analysis of modified Rankin Scale at day 90 in moderate to severe patients resulted in MW 0.61 with statistical significance in favor of Cerebrolysin (95% CI 0.52 to 0.69, P = 0.0118, N = 314). Safety aspects were comparable to placebo. Our meta-analysis confirms previous evidence that Cerebrolysin has a beneficial effect on early global neurological deficits in patients with acute ischemic stroke.

Zheng Gang Zhang - One of the best experts on this subject based on the ideXlab platform.

  • therapeutic effect of Cerebrolysin on reducing impaired cerebral endothelial cell permeability
    Neuroreport, 2021
    Co-Authors: Hua Teng, Yi Zhang, Michael Chopp, Zheng Gang Zhang, Melanie Melchermourgas, Burkhard Fleckenstein
    Abstract:

    Cerebrolysin has been shown to promote neurovascular protection and repair in preclinical models of stroke and neural injury and is demonstrating promise for stroke and neural injury therapeutic application in the clinic. The effect of Cerebrolysin on the human cerebral endothelial cell function has not been investigated. Using an in-vitro cerebral endothelial cell permeability assay and western blot analyses of tight junction and proinflammatory and procoagulant proteins, the present study showed that tissue plasminogen activator (tPA) and fibrin substantially impaired human cerebral endothelial cell barrier function and increased permeability, which persisted for at least 24 h. western blot analysis revealed that tPA and fibrin significantly increased proinflammatory and procoagulation proteins of intercellular adhesion molecule 1, high mobility group box 1, tumor necrosis factor α and phosphorylated nuclear factor kappa B-p65, and significantly reduced tight junction proteins zonular 1, occludin and claudin. However, Cerebrolysin significantly diminished and reversed tPA- and fibrin-impaired endothelial cell permeability, which was associated with significant reductions of tPA- and fibrin-augmented proinflammatory and procoagulation proteins and significant elevations of tPA- and fibrin-decreased tight junction proteins. The beneficial effect of Cerebrolysin appears specific because cerebroprotein hydrolysate, with a distinct peptide composition, failed to show the reduction of tPA- and fibrin-impaired permeability. These data indicate that cererbrolysin has a therapeutic effect on tPA- and fibrin-impaired cerebral endothelial cell permeability by reducing proinflammatory and procoagulation proteins and by elevating tight junction proteins.

  • randomized controlled trial of Cerebrolysin s effects on long term histological outcomes and functional recovery in rats with moderate closed head injury
    Journal of Neurosurgery, 2020
    Co-Authors: Yanlu Zhang, Yi Zhang, Michael Chopp, Zheng Gang Zhang, Li Zhang, Talan Zhang, Asim Mahmood, Ye Xiong
    Abstract:

    OBJECTIVE The authors previously demonstrated that Cerebrolysin is effective for treatment of mild closed head injury (CHI) when administered 4 hours after injury. The aim of this study was to determine Cerebrolysin's effects on functional and histological outcomes in rats subjected to moderate CHI. METHODS In this randomized, blinded, and vehicle-controlled preclinical trial, male adult Wistar rats subjected to moderate CHI received either Cerebrolysin treatment at a dose of 2.5 ml/kg (n = 13) or vehicle (saline, n = 13) intraperitoneally administered daily for 10 days, starting at 4 hours after injury. Animals were subjected to cognitive and sensorimotor functional tests at multiple time points, and they were killed 3 months after injury. The brains were processed for analyses of neuronal cell loss, amyloid precursor protein, axonal damage, and neurogenesis. RESULTS Compared with rats treated with vehicle (saline), rats treated with Cerebrolysin had significantly increased numbers of neuroblasts and newborn mature neurons in the dentate gyrus (DG) and attenuated amyloid precursor protein accumulation and axonal damage in various brain regions, as well as decreased neuronal loss in the DG and cornu ammonis 3 (CA3) region of the hippocampus (p < 0.05). Global testing using generalized estimating equations showed a significant beneficial effect of Cerebrolysin treatment on sensorimotor functional outcomes from 1 day to 3 months after injury compared to that of saline treatment (p < 0.05). Compared with vehicle-treated rats, Cerebrolysin-treated rats showed significantly and robustly improved long-term (up to 3 months) cognitive functional recovery, as measured by social interaction, Morris water maze, novel object recognition, and odor recognition tests. In the Cerebrolysin-treated rats there were significant correlations between multiple histological outcomes and functional recovery evident 3 months after moderate CHI, as indicated by Pearson partial correlation analyses. CONCLUSIONS The authors' findings demonstrate that Cerebrolysin treatment significantly improves long-term functional and histological outcomes in rats with moderate CHI, with functional outcomes significantly correlated with histological indices of neuroplasticity and neuroprotection. These data indicate that Cerebrolysin may be useful for the treatment of moderate CHI.

  • prospective double blinded comparative assessment of the pharmacological activity of Cerebrolysin and distinct peptide preparations for the treatment of embolic stroke
    Journal of the Neurological Sciences, 2019
    Co-Authors: Li Zhang, Yi Zhang, Michael Chopp, Talan Zhang, Chunyang Wang, Zheng Gang Zhang
    Abstract:

    Abstract Background Our previous work in acute ischemic stroke and TBI models focused on efficacy and pharmacological parameters of Cerebrolysin®. In this prospective, randomized, blinded, placebo-controlled study we compared efficacy of neuropeptide preparations with putative neurotrophic potential to the reference product Cerebrolysin® by assessing functional outcome and lesion volumes after embolic stroke in a rodent model. Methods Male Wistar rats were subjected to embolic right middle cerebral artery occlusion and were treated with: 1) Cognistar® (Cerebroprotein Hydrolysate) 2.5 ml/kg, 2) Cerebrolysat® 2.5 ml/kg, 3) Cortexin® 1.7 mg/kg, 4) Cerebrolysin® 2.5 ml/kg, or 5) 1 ml of saline according to a pre-generated randomization plan. Dosages were defined according to the packet leaflet of the corresponding preparation and were adapted to the animal model as previously described. All enrolled rats received intraperitoneal injections once daily for 10 consecutive days, starting 4 h after occlusion. Functional outcome was assessed once weekly over four weeks by using a battery of behavioral tests. Infarct volume was measured four weeks after occlusion. Generalized Estimation Equations (GEE) was performed to study the treatment effect on overall functional recovery at day 28 (primary outcome), compared to saline controls. Results Similar functional outcome was observed for saline control, Cognistar®, Cerebrolysat® and Cortexin®; in contrast, a significantly improved neurological outcome was observed with Cerebrolysin® treatment in comparison to saline as well as to the comparator drug treatment (p  Conclusion Among all tested neuropeptide preparations, Cerebrolysin® was the only agent that was associated with a significant improvement of neurological outcome after stroke.

  • Cerebrolysin reduces astrogliosis and axonal injury and enhances neurogenesis in rats after closed head injury
    Neurorehabilitation and Neural Repair, 2019
    Co-Authors: Yanlu Zhang, Yi Zhang, Michael Chopp, Zheng Gang Zhang, Li Zhang, Stefan Winter, Mei Lu, Talan Zhang, Edith Doppler
    Abstract:

    Background. Cerebrolysin is a neuropeptide preparation with neuroprotective and neurotrophic properties. Our previous study demonstrates that Cerebrolysin significantly improves functional recovery...

  • prospective randomized blinded and placebo controlled study of Cerebrolysin dose response effects on long term functional outcomes in a rat model of mild traumatic brain injury
    Journal of Neurosurgery, 2018
    Co-Authors: Yanlu Zhang, Yi Zhang, Michael Chopp, Zheng Gang Zhang, Li Zhang, Stefan Winter, Talan Zhang, Asim Mahmood, Hemma Brandstatter, Ye Xiong
    Abstract:

    Using a prospective, randomized, blinded, placebo-controlled protocol, the authors demonstrated that Cerebrolysin at doses of 0.8-7.5 ml/kg, administered 4 hours after injury and then once daily for a total of 10 consecutive days, improves long-term functional outcomes in a rat model of mild closed head injury; a 2.5-ml/kg dose was identified as optimal. These findings suggest that Cerebrolysin has the potential to treat mild traumatic brain injury, the incidence of which is high without effective treatments.

Michael Chopp - One of the best experts on this subject based on the ideXlab platform.

  • therapeutic effect of Cerebrolysin on reducing impaired cerebral endothelial cell permeability
    Neuroreport, 2021
    Co-Authors: Hua Teng, Yi Zhang, Michael Chopp, Zheng Gang Zhang, Melanie Melchermourgas, Burkhard Fleckenstein
    Abstract:

    Cerebrolysin has been shown to promote neurovascular protection and repair in preclinical models of stroke and neural injury and is demonstrating promise for stroke and neural injury therapeutic application in the clinic. The effect of Cerebrolysin on the human cerebral endothelial cell function has not been investigated. Using an in-vitro cerebral endothelial cell permeability assay and western blot analyses of tight junction and proinflammatory and procoagulant proteins, the present study showed that tissue plasminogen activator (tPA) and fibrin substantially impaired human cerebral endothelial cell barrier function and increased permeability, which persisted for at least 24 h. western blot analysis revealed that tPA and fibrin significantly increased proinflammatory and procoagulation proteins of intercellular adhesion molecule 1, high mobility group box 1, tumor necrosis factor α and phosphorylated nuclear factor kappa B-p65, and significantly reduced tight junction proteins zonular 1, occludin and claudin. However, Cerebrolysin significantly diminished and reversed tPA- and fibrin-impaired endothelial cell permeability, which was associated with significant reductions of tPA- and fibrin-augmented proinflammatory and procoagulation proteins and significant elevations of tPA- and fibrin-decreased tight junction proteins. The beneficial effect of Cerebrolysin appears specific because cerebroprotein hydrolysate, with a distinct peptide composition, failed to show the reduction of tPA- and fibrin-impaired permeability. These data indicate that cererbrolysin has a therapeutic effect on tPA- and fibrin-impaired cerebral endothelial cell permeability by reducing proinflammatory and procoagulation proteins and by elevating tight junction proteins.

  • randomized controlled trial of Cerebrolysin s effects on long term histological outcomes and functional recovery in rats with moderate closed head injury
    Journal of Neurosurgery, 2020
    Co-Authors: Yanlu Zhang, Yi Zhang, Michael Chopp, Zheng Gang Zhang, Li Zhang, Talan Zhang, Asim Mahmood, Ye Xiong
    Abstract:

    OBJECTIVE The authors previously demonstrated that Cerebrolysin is effective for treatment of mild closed head injury (CHI) when administered 4 hours after injury. The aim of this study was to determine Cerebrolysin's effects on functional and histological outcomes in rats subjected to moderate CHI. METHODS In this randomized, blinded, and vehicle-controlled preclinical trial, male adult Wistar rats subjected to moderate CHI received either Cerebrolysin treatment at a dose of 2.5 ml/kg (n = 13) or vehicle (saline, n = 13) intraperitoneally administered daily for 10 days, starting at 4 hours after injury. Animals were subjected to cognitive and sensorimotor functional tests at multiple time points, and they were killed 3 months after injury. The brains were processed for analyses of neuronal cell loss, amyloid precursor protein, axonal damage, and neurogenesis. RESULTS Compared with rats treated with vehicle (saline), rats treated with Cerebrolysin had significantly increased numbers of neuroblasts and newborn mature neurons in the dentate gyrus (DG) and attenuated amyloid precursor protein accumulation and axonal damage in various brain regions, as well as decreased neuronal loss in the DG and cornu ammonis 3 (CA3) region of the hippocampus (p < 0.05). Global testing using generalized estimating equations showed a significant beneficial effect of Cerebrolysin treatment on sensorimotor functional outcomes from 1 day to 3 months after injury compared to that of saline treatment (p < 0.05). Compared with vehicle-treated rats, Cerebrolysin-treated rats showed significantly and robustly improved long-term (up to 3 months) cognitive functional recovery, as measured by social interaction, Morris water maze, novel object recognition, and odor recognition tests. In the Cerebrolysin-treated rats there were significant correlations between multiple histological outcomes and functional recovery evident 3 months after moderate CHI, as indicated by Pearson partial correlation analyses. CONCLUSIONS The authors' findings demonstrate that Cerebrolysin treatment significantly improves long-term functional and histological outcomes in rats with moderate CHI, with functional outcomes significantly correlated with histological indices of neuroplasticity and neuroprotection. These data indicate that Cerebrolysin may be useful for the treatment of moderate CHI.

  • prospective double blinded comparative assessment of the pharmacological activity of Cerebrolysin and distinct peptide preparations for the treatment of embolic stroke
    Journal of the Neurological Sciences, 2019
    Co-Authors: Li Zhang, Yi Zhang, Michael Chopp, Talan Zhang, Chunyang Wang, Zheng Gang Zhang
    Abstract:

    Abstract Background Our previous work in acute ischemic stroke and TBI models focused on efficacy and pharmacological parameters of Cerebrolysin®. In this prospective, randomized, blinded, placebo-controlled study we compared efficacy of neuropeptide preparations with putative neurotrophic potential to the reference product Cerebrolysin® by assessing functional outcome and lesion volumes after embolic stroke in a rodent model. Methods Male Wistar rats were subjected to embolic right middle cerebral artery occlusion and were treated with: 1) Cognistar® (Cerebroprotein Hydrolysate) 2.5 ml/kg, 2) Cerebrolysat® 2.5 ml/kg, 3) Cortexin® 1.7 mg/kg, 4) Cerebrolysin® 2.5 ml/kg, or 5) 1 ml of saline according to a pre-generated randomization plan. Dosages were defined according to the packet leaflet of the corresponding preparation and were adapted to the animal model as previously described. All enrolled rats received intraperitoneal injections once daily for 10 consecutive days, starting 4 h after occlusion. Functional outcome was assessed once weekly over four weeks by using a battery of behavioral tests. Infarct volume was measured four weeks after occlusion. Generalized Estimation Equations (GEE) was performed to study the treatment effect on overall functional recovery at day 28 (primary outcome), compared to saline controls. Results Similar functional outcome was observed for saline control, Cognistar®, Cerebrolysat® and Cortexin®; in contrast, a significantly improved neurological outcome was observed with Cerebrolysin® treatment in comparison to saline as well as to the comparator drug treatment (p  Conclusion Among all tested neuropeptide preparations, Cerebrolysin® was the only agent that was associated with a significant improvement of neurological outcome after stroke.

  • Cerebrolysin reduces astrogliosis and axonal injury and enhances neurogenesis in rats after closed head injury
    Neurorehabilitation and Neural Repair, 2019
    Co-Authors: Yanlu Zhang, Yi Zhang, Michael Chopp, Zheng Gang Zhang, Li Zhang, Stefan Winter, Mei Lu, Talan Zhang, Edith Doppler
    Abstract:

    Background. Cerebrolysin is a neuropeptide preparation with neuroprotective and neurotrophic properties. Our previous study demonstrates that Cerebrolysin significantly improves functional recovery...

  • prospective randomized blinded and placebo controlled study of Cerebrolysin dose response effects on long term functional outcomes in a rat model of mild traumatic brain injury
    Journal of Neurosurgery, 2018
    Co-Authors: Yanlu Zhang, Yi Zhang, Michael Chopp, Zheng Gang Zhang, Li Zhang, Stefan Winter, Talan Zhang, Asim Mahmood, Hemma Brandstatter, Ye Xiong
    Abstract:

    Using a prospective, randomized, blinded, placebo-controlled protocol, the authors demonstrated that Cerebrolysin at doses of 0.8-7.5 ml/kg, administered 4 hours after injury and then once daily for a total of 10 consecutive days, improves long-term functional outcomes in a rat model of mild closed head injury; a 2.5-ml/kg dose was identified as optimal. These findings suggest that Cerebrolysin has the potential to treat mild traumatic brain injury, the incidence of which is high without effective treatments.

Li Zhang - One of the best experts on this subject based on the ideXlab platform.

  • randomized controlled trial of Cerebrolysin s effects on long term histological outcomes and functional recovery in rats with moderate closed head injury
    Journal of Neurosurgery, 2020
    Co-Authors: Yanlu Zhang, Yi Zhang, Michael Chopp, Zheng Gang Zhang, Li Zhang, Talan Zhang, Asim Mahmood, Ye Xiong
    Abstract:

    OBJECTIVE The authors previously demonstrated that Cerebrolysin is effective for treatment of mild closed head injury (CHI) when administered 4 hours after injury. The aim of this study was to determine Cerebrolysin's effects on functional and histological outcomes in rats subjected to moderate CHI. METHODS In this randomized, blinded, and vehicle-controlled preclinical trial, male adult Wistar rats subjected to moderate CHI received either Cerebrolysin treatment at a dose of 2.5 ml/kg (n = 13) or vehicle (saline, n = 13) intraperitoneally administered daily for 10 days, starting at 4 hours after injury. Animals were subjected to cognitive and sensorimotor functional tests at multiple time points, and they were killed 3 months after injury. The brains were processed for analyses of neuronal cell loss, amyloid precursor protein, axonal damage, and neurogenesis. RESULTS Compared with rats treated with vehicle (saline), rats treated with Cerebrolysin had significantly increased numbers of neuroblasts and newborn mature neurons in the dentate gyrus (DG) and attenuated amyloid precursor protein accumulation and axonal damage in various brain regions, as well as decreased neuronal loss in the DG and cornu ammonis 3 (CA3) region of the hippocampus (p < 0.05). Global testing using generalized estimating equations showed a significant beneficial effect of Cerebrolysin treatment on sensorimotor functional outcomes from 1 day to 3 months after injury compared to that of saline treatment (p < 0.05). Compared with vehicle-treated rats, Cerebrolysin-treated rats showed significantly and robustly improved long-term (up to 3 months) cognitive functional recovery, as measured by social interaction, Morris water maze, novel object recognition, and odor recognition tests. In the Cerebrolysin-treated rats there were significant correlations between multiple histological outcomes and functional recovery evident 3 months after moderate CHI, as indicated by Pearson partial correlation analyses. CONCLUSIONS The authors' findings demonstrate that Cerebrolysin treatment significantly improves long-term functional and histological outcomes in rats with moderate CHI, with functional outcomes significantly correlated with histological indices of neuroplasticity and neuroprotection. These data indicate that Cerebrolysin may be useful for the treatment of moderate CHI.

  • prospective double blinded comparative assessment of the pharmacological activity of Cerebrolysin and distinct peptide preparations for the treatment of embolic stroke
    Journal of the Neurological Sciences, 2019
    Co-Authors: Li Zhang, Yi Zhang, Michael Chopp, Talan Zhang, Chunyang Wang, Zheng Gang Zhang
    Abstract:

    Abstract Background Our previous work in acute ischemic stroke and TBI models focused on efficacy and pharmacological parameters of Cerebrolysin®. In this prospective, randomized, blinded, placebo-controlled study we compared efficacy of neuropeptide preparations with putative neurotrophic potential to the reference product Cerebrolysin® by assessing functional outcome and lesion volumes after embolic stroke in a rodent model. Methods Male Wistar rats were subjected to embolic right middle cerebral artery occlusion and were treated with: 1) Cognistar® (Cerebroprotein Hydrolysate) 2.5 ml/kg, 2) Cerebrolysat® 2.5 ml/kg, 3) Cortexin® 1.7 mg/kg, 4) Cerebrolysin® 2.5 ml/kg, or 5) 1 ml of saline according to a pre-generated randomization plan. Dosages were defined according to the packet leaflet of the corresponding preparation and were adapted to the animal model as previously described. All enrolled rats received intraperitoneal injections once daily for 10 consecutive days, starting 4 h after occlusion. Functional outcome was assessed once weekly over four weeks by using a battery of behavioral tests. Infarct volume was measured four weeks after occlusion. Generalized Estimation Equations (GEE) was performed to study the treatment effect on overall functional recovery at day 28 (primary outcome), compared to saline controls. Results Similar functional outcome was observed for saline control, Cognistar®, Cerebrolysat® and Cortexin®; in contrast, a significantly improved neurological outcome was observed with Cerebrolysin® treatment in comparison to saline as well as to the comparator drug treatment (p  Conclusion Among all tested neuropeptide preparations, Cerebrolysin® was the only agent that was associated with a significant improvement of neurological outcome after stroke.

  • Cerebrolysin reduces astrogliosis and axonal injury and enhances neurogenesis in rats after closed head injury
    Neurorehabilitation and Neural Repair, 2019
    Co-Authors: Yanlu Zhang, Yi Zhang, Michael Chopp, Zheng Gang Zhang, Li Zhang, Stefan Winter, Mei Lu, Talan Zhang, Edith Doppler
    Abstract:

    Background. Cerebrolysin is a neuropeptide preparation with neuroprotective and neurotrophic properties. Our previous study demonstrates that Cerebrolysin significantly improves functional recovery...

  • Cerebrolysin Ameliorates BBB Leakage and Microvascular Inflammation Induced by tPA and Fibrin
    Henry Ford Health System Scholarly Commons, 2019
    Co-Authors: Chopp Michael, Li Zhang, Li Chao, Teng Hua, Gang Zhang Zheng
    Abstract:

    Background and aims: Fibrin deposition post stroke and thrombolysis with tPA induce blood brain barrier (BBB) permeability and subsequent perfusion deficits and proinflammatory conditions. Here, using a human brain cerebral endothelial cell BBB assay, we investigated the effect of Cerebrolysin on BBB integrity and its underlying molecular contributions to ameliorating vascular permeability induced by tPA and fibrin. Methods: Human primary brain endothelial cells (150,000/ cm2) were seeded onto a transwell and treated with tPA (10ug/ml) or fibrin (1.5ug/ml), alone or with Cerebrolysin (5, 10, 20, 40, 80 ul/ml; n=3 per experiment). Leakage of FITC-labeled dextran (70KD) into a bottom chamber of the transwell was quantified. Results: Treatment of human cerebral endothelial cells with fibrin and tPA significantly (p\u3c0.05) increased BBB leakage by 37% and 57%, respectively, compared to the nontreatment group (n-3/group). However, Cerebrolysin in a dose-dependent manner significantly decreased fibrin- or tPA-induced leakage, respectively, at a dose of 20 ul/ms. Western blot analysis showed that compared to non-treated control, fibrin and tPA alone markedly augmented proinflammatory proteins, i.e., HMGB1 ICAM-1, TNFα, and pNFκB. However, Cerebrolysin significantly (P\u3c0.05) decreased these elevated adverse proinflammatory proteins. Conclusion: Cerebrolysin reduces BBB permeability induced by tPA and fibrin. Our data also provide molecular bases for the beneficial effect of Cerebrolysin on reduction of BBB leakage. Thus, in vivo studies employing Cerebrolysin in combination with tPA and/or thrombectomy for the treatment of stroke are warranted

  • prospective randomized blinded and placebo controlled study of Cerebrolysin dose response effects on long term functional outcomes in a rat model of mild traumatic brain injury
    Journal of Neurosurgery, 2018
    Co-Authors: Yanlu Zhang, Yi Zhang, Michael Chopp, Zheng Gang Zhang, Li Zhang, Stefan Winter, Talan Zhang, Asim Mahmood, Hemma Brandstatter, Ye Xiong
    Abstract:

    Using a prospective, randomized, blinded, placebo-controlled protocol, the authors demonstrated that Cerebrolysin at doses of 0.8-7.5 ml/kg, administered 4 hours after injury and then once daily for a total of 10 consecutive days, improves long-term functional outcomes in a rat model of mild closed head injury; a 2.5-ml/kg dose was identified as optimal. These findings suggest that Cerebrolysin has the potential to treat mild traumatic brain injury, the incidence of which is high without effective treatments.

Hari Shanker Sharma - One of the best experts on this subject based on the ideXlab platform.

  • nanodelivery of Cerebrolysin reduces pathophysiology of parkinson s disease
    Progress in Brain Research, 2019
    Co-Authors: Asya Ozkizilcik, Dafin F Muresanu, Aruna Sharma, Jose Vicente Lafuente, Herbert Mossler, Ryan Z Tian, Rudy J Castellani, Ala Nozari, Hari Shanker Sharma
    Abstract:

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

  • sleep deprivation induced blood brain barrier breakdown and brain pathology neuroprotective effects of tio2 nanowired delivery of Cerebrolysin and ondansetron
    2017
    Co-Authors: Aruna Sharma, Dafin F Muresanu, Jose Vicente Lafuente, Anca Dana Buzoianu, Ryan Z Tian, Asya Ozkizilcik, Hari Shanker Sharma
    Abstract:

    Military personnel are often subjected to sleep deprivation (SD) for long hours during combat or peacekeeping operations across the Globe. Recent reports suggests that sound sleep for less than 4 h results in confusion, simple task calculations, and affects decision making. However, in military life SD of 12–72 h is quite common. It appears that longer duration of SD is related to brain dysfunction. Model experiments carried out in our laboratory show that 12–72 h of SD in rats results in progressive breakdown of the blood-brain barrier (BBB) to proteins and induce brain edema formation. Selective neuronal, glial cell and axonal injuries also occurred in SD that is progressive in nature. Interestingly, the magnitude and intensity of SD depends on environmental temperature and cardiovascular health of the animals. Thus, SD at 34 °C induces 2- to 4- fold brain damage, BBB breakdown and edema formation in rats as compared to identical SD at room temperature (21 ± 1 °C). Also hypertensive rats when subjected to identical SD showed greater degree of brain pathology as compared to normotensive animals. Treatment with a multimodal drug Cerebrolysin that is a balanced composition of several neurotrophic factors and active peptide fragments significantly reduced the brain pathology in healthy animals at room temperature. However, TiO2-nanowired delivery of Cerebrolysin is needed to attenuate SD induced brain pathology of normotensive rats at hot environment or hypertensive animals at room temperature. These observations suggest that nanodrug delivery in SD is needed to induce neuroprotection at hot environment or in hypertensive animals, not reported earlier.

  • intravenous administration of functionalized magnetic iron oxide nanoparticles does not induce cns injury in the rat influence of spinal cord trauma and Cerebrolysin treatment
    International Review of Neurobiology, 2017
    Co-Authors: Preeti K Menon, Hari Shanker Sharma, Dafin F Muresanu, Ranjana Patnaik, Aruna Sharma, Jose Vicente Lafuente, Zoraida P Aguilar, Anderw Y Wang, Herbert Mossler
    Abstract:

    Influence of iron oxide magnetic nanoparticles (IOMNPs, 10nm in diameter, 0.25 or 0.50mg/mL in 100μL, i.v.) on the blood-brain barrier (BBB) permeability, edema formation, and neuronal or glial changes within 4-24h after administration was examined in normal rats and after a focal spinal cord injury (SCI). Furthermore, effect of Cerebrolysin, a balanced composition of several neurotrophic factors, and active peptide fragments was also evaluated on IOMNP-induced changes in central nervous system (CNS) pathology. The SCI was inflicted in rats by making a longitudinal incision into the right dorsal horn of the T10-11 segments and allowed to survive 4 or 24h after trauma. Cerebrolysin (2.5mL/kg, i.v.) was given either 30min before IOMNP injection in the 4-h SCI group or 4h after injury in the 24-h survival groups. Control group received Cerebrolysin in identical situation following IOMNP administration. In all groups, leakage of serum albumin in the CNS as a marker of BBB breakdown and activation of astrocytes using glial fibrillary acidic protein was evaluated by immunohistochemistry. The neuronal injury was examined by Nissl staining. The IOMNPs alone in either low or high doses did not induce CNS pathology either following 4 or 24h after administration. However, administration of IOMNPs in SCI group slightly enhanced the pathological changes in the CNS after 24h but not 4h after trauma. Cerebrolysin treatment markedly attenuated IOMNP-induced aggravation of SCI-induced cord pathology and induced significant neuroprotection. These observations are the first to show that IOMNPs are safe for the CNS and Cerebrolysin treatment prevented CNS pathology following a combination of trauma and IOMNP injection. This indicated that Cerebrolysin might be used as adjunct therapy during IOMNP administration in disease conditions, not reported earlier.

  • the role of functionalized magnetic iron oxide nanoparticles in the central nervous system injury and repair new potentials for neuroprotection with Cerebrolysin therapy
    Journal of Nanoscience and Nanotechnology, 2014
    Co-Authors: Hari Shanker Sharma, Dafin F Muresanu, Ranjana Patnaik, Preeti K Menon, Jose Vicente Lafuente, Zoraida P Aguilar, Anderw Y Wang, Herbert Mossler, Aruna Sharma
    Abstract:

    Functionalized Magnetic Iron Oxide Nanoparticles (FMIONPs) are being explored for the development of various biomedical applications, e.g., cancer chemotherapy and/or several other radiological or diagnostic purposes. However, the effects of these NPs per se on the central nervous system (CNS) injury or repair are not well known. This review deals with different aspects of FMIONPs in relation to brain function based on the current literature as well as our own investigation in animal models of CNS injuries. It appears that FMIONPs are innocuous when administered intravenously within the CNS under normal conditions. However, abnormal reactions to FMIONPs in the brain or spinal cord could be seen if they are combined with CNS injuries e.g., hyperthermia or traumatic insults to the brain or spinal cord. Thus, administration of FMIONPs in vivo following whole body hyperthermia (WBH) or a focal spinal cord injury (SCI) exacerbates cellular damage. Since FMIONPs could help in diagnostic purposes or enhance the biological effects of radiotherapy/chemotherapy it is likely that these NPs may have some adverse reaction as well under disease condition. Thus, under such situation, adjuvant therapy e.g., Cerebrolysin (Ever NeuroPharma, Austria), a suitable combination of several neurotrophic factors and active peptide fragments are the need of the hour to contain such cellular damages caused by the FMIONPs in vivo. Our observations show that co-administration of Cerebrolysin prevents the FMIONPs induced pathologies associated with CNS injuries. These observations support the idea that FMIONPs are safe for the CNS in disease conditions when co-administered with Cerebrolysin. This indicates that Cerebrolysin could be used as an adjunct therapy to prevent cellular damages in disease conditions where the use of FMIONPs is required for better efficacy e.g., cancer treatment.

  • Cerebrolysin a mixture of neurotrophic factors induces marked neuroprotection in spinal cord injury following intoxication of engineered nanoparticles from metals
    Cns & Neurological Disorders-drug Targets, 2012
    Co-Authors: Preeti K Menon, Aruna Sharma, Dafin F Muresanu, Herbert Mossler, Hari Shanker Sharma
    Abstract:

    Spinal cord injury (SCI) is the world's most disastrous disease for which there is no effective treatment till today. Several studies suggest that nanoparticles could adversely influence the pathology of SCI and thereby alter the efficacy of many neuroprotective agents. Thus, there is an urgent need to find suitable therapeutic agents that could minimize cord pathology following trauma upon nanoparticle intoxication. Our laboratory has been engaged for the last 7 years in finding suitable therapeutic strategies that could equally reduce cord pathology in normal and in nanoparticle-treated animal models of SCI. We observed that engineered nanoparticles from metals e.g., aluminum (Al), silver (Ag) and copper (Cu) (50-60 nm) when administered in rats daily for 7 days (50 mg/kg, i.p.) resulted in exacerbation of cord pathology after trauma that correlated well with breakdown of the blood-spinal cord barrier (BSCB) to serum proteins. The entry of plasma proteins into the cord leads to edema formation and neuronal damage. Thus, future drugs should be designed in such a way to be effective even when the SCI is influenced by nanoparticles. Previous research suggests that a suitable combination of neurotrophic factors could induce marked neuroprotection in SCI in normal animals. Thus, we examined the effects of a new drug; Cerebrolysin that is a mixture of different neurotrophic factors e.g., brain-derived neurotrophic factor (BDNF), glial cell line derived neurotrophic factor (GDNF), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF) and other peptide fragments to treat normal or nanoparticle-treated rats after SCI. Our observations showed that Cerebrolysin (2.5 ml/kg, i.v.) before SCI resulted in good neuroprotection in normal animals, whereas nanoparticle-treated rats required a higher dose of the drug (5.0 ml/kg, i.v.) to induce comparable neuroprotection in the cord after SCI. Cerebrolysin also reduced spinal cord water content, leakage of plasma proteins and the number of injured neurons. This indicates that Cerebrolysin in higher doses could be a good candidate for treating SCI cases following nanoparticle intoxication. The possible mechanisms and functional significance of these findings are discussed in this review.