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      Neuropsychiatric Disease and Treatment (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on all aspects of neuropsychiatric and neurological disorders. Sign up for email alerts here.

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      Cerebrolysin effects on neurological outcomes and cerebral blood flow in acute ischemic stroke

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          Abstract

          Background

          Cerebrolysin, a brain-derived neuropeptide, has been shown to improve the neurological outcomes of stroke, but no study has demonstrated its effect on cerebral blood flow. This study aimed to determine the cerebrolysin impact on the neurological outcomes and cerebral blood flow.

          Methods

          In a randomized, double-blinded, placebo-controlled trial, 46 patients who had acute focal ischemic stroke were randomly assigned into two groups to receive intravenously either 30 mL of cerebrolysin diluted in normal saline daily for 10 days (n=23) or normal saline alone (n=23) adjunct to 100 mg of aspirin daily. All patients were examined using the National Institutes of Health Stroke Scale and transcranial Doppler to measure the mean flow velocity and pulsatility index (PI) of their cerebral arteries at baseline as well as on days 30, 60, and 90.

          Results

          The patients’ mean age was 60±9.7 years, and 51.2% of patients were male. The National Institutes of Health Stroke Scale was significantly lower in the cerebrolysin group compared with the placebo group on day 60 (median 10, interquartile range 9–11, P=0.008) and day 90 (median 11, interquartile range 10–13.5, P=0.001). The median of PI in the right middle cerebral artery was significantly lower in the cerebrolysin group compared with the placebo group on days 30, 60, and 90 ( P<0.05). One patient in the cerebrolysin group and two patients in the placebo group died before day 30 (4.3% versus 8.7%).

          Conclusion

          Cerebrolysin can be useful to improve the neurological outcomes and the PI of middle cerebral artery in patients with acute focal ischemic stroke.

          Most cited references26

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          Stroke Treatment Academic Industry Roundtable (STAIR) recommendations for maximizing the use of intravenous thrombolytics and expanding treatment options with intra-arterial and neuroprotective therapies.

          The goal of the Stroke Treatment Academic Industry Roundtable (STAIR) meetings is to advance the development of acute and restorative stroke therapies. Summary of Review- At the STAIR VII recommendations for strategies to maximize the use of intravenous thrombolytics through targeting public education, and the refinement of current treatment exclusion criteria were proposed. Increased utilization of mechanical devices for intra-arterial recanalization can be achieved by obtaining more definitive evidence of efficacy in randomized clinical trials, identification of patient characteristics associated with treatment efficacy, optimization of technical approaches, clarification of effective time windows, and development of approaches to limit complications. Neuroprotective strategies remain viable; recommendations for further study of these agents include an emphasis on rapid administration, consideration of the systemic effects of ischemic stroke, prevention of complications associated with early reperfusion, a focus on agents with multiple mechanisms of action, and consideration of possible interactions between neuroprotective and thrombolytic therapies. Extending intravenous thrombolysis to a broader patient population, clarifying the risk and benefits of intra-arterial reperfusion therapies, and further development of neuroprotective therapies were the key recommendations from STAIR VII.
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            Medical treatment in acute and long-term secondary prevention after transient ischaemic attack and ischaemic stroke.

            Stroke is a major cause of death and disability worldwide. Without improvements in prevention, the burden will increase during the next 20 years because of the ageing population, especially in developing countries. Major advances have occurred in secondary prevention during the past three decades, which demonstrate the broader potential to prevent stroke. We review the main medical treatments that should be considered for most patients with transient ischaemic attack or ischaemic stroke in the acute phase and the long term, and draw attention to recent developments. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              Cerebrolysin enhances neurogenesis in the ischemic brain and improves functional outcome after stroke.

              Cerebrolysin is a peptide preparation mimicking the action of neurotrophic factors and has beneficial effects on neurodegenerative diseases and stroke. The present study investigated the effect of Cerebrolysin on neurogenesis in a rat model of embolic middle cerebral artery occlusion (MCAo). Treatment with Cerebrolysin at doses of 2.5 and 5 ml/kg significantly increased the number of bromodeoxyuridine-positive (BrdU(+)) subventricular zone (SVZ) neural progenitor cells and doublecortin (DCX) immunoreactivity (migrating neuroblasts) in the ipsilateral SVZ and striatal ischemic boundary 28 days after stroke when the treatment was initiated 24 hr after stroke. The treatment also reduced TUNEL(+) cells by ∼50% in the ischemic boundary. However, treatment with Cerebrolysin at a dose of 2.5 ml/kg initiated at 24 and 48 hr did not significantly reduce infarct volume but substantially improved neurological outcomes measured by an array of behavioral tests 21 and 28 days after stroke. Incubation of SVZ neural progenitor cells from ischemic rats with Cerebrolysin dose dependently augmented BrdU(+) cells and increased the number of Tuj1(+) cells (a marker of immature neurons). Blockage of the PI3K/Akt pathway abolished Cerebrolysin-increased BrdU(+) cells. Moreover, Cerebrolysin treatment promoted neural progenitor cell migration. Collectively, these data indicate that Cerebrolysin treatment when initiated 24 and 48 hr after stroke enhances neurogenesis in the ischemic brain and improves functional outcome and that Cerebrolysin-augmented proliferation, differentiation, and migration of adult SVZ neural progenitor cells contribute to Cerebrolysin-induced neurogenesis, which may be related to improvement of neurological outcome. The PI3K/Akt pathway mediates Cerebrolysin-induced progenitor cell proliferation.
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                Author and article information

                Journal
                Neuropsychiatr Dis Treat
                Neuropsychiatric Disease and Treatment
                Neuropsychiatric Disease and Treatment
                Dove Medical Press
                1176-6328
                1178-2021
                2014
                03 December 2014
                : 10
                : 2299-2306
                Affiliations
                [1 ]Department of Neurology, Imam Khomeini Hospital, Urmia University of Medical Sciences, Urmia, Iran
                [2 ]School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
                [3 ]Seyyed-al-Shohada Heart Center, Urmia University of Medical Sciences, Urmia, Iran
                Author notes
                Correspondence: Yousef Rezaei, Seyyed-al-Shohada Heart Center, 17 Shahrivar Boulevard, Urmia 5718749441, Iran, Tel +98 912 623 1864, Fax +98 441 237 5907, Email yousefrezaei1986@ 123456gmail.com
                Article
                ndt-10-2299
                10.2147/NDT.S75304
                4263193
                25516711
                5f4879c7-4794-4fe0-9673-f548e055a2c4
                © 2014 Amiri-Nikpour et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Neurology
                ischemic stroke,cerebrolysin,neuroprotection,nihss,mean flow velocity,pulsatility index
                Neurology
                ischemic stroke, cerebrolysin, neuroprotection, nihss, mean flow velocity, pulsatility index

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