Dafin F Muresanu

Universitatea de Medicina si Farmacie Craiova, Croiova, Dolj, Romania

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Publications (83)148.43 Total impact

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    ABSTRACT: In this study, we examined the influence of cold and hot environments on methamphetamine (METH) neurotoxicity in both drug-naive rats and animals previously exposed to different types of nanoparticles (NPs). Since METH induces oxidative stress, we also examined how a potential chain-breaking antioxidant H-290/51 (Astra-Zeneca, Mölndal, Sweden) affects METH-induced neurotoxicity. Exposure of drug-naive rats to METH (9 mg/kg, s.c.) at 4, 21, or 34 °C for 3 h resulted in breakdown of the blood-brain barrier (BBB), brain edema, and neuronal injuries, which all differed in severity depending upon ambient temperatures. The changes were moderate at 21 °C, 120-180 % larger at 34 °C, and almost absent at 4 °C. In rats chronically treated with NPs (SiO2, Cu, or Ag; 50-60 nm, 50 mg/kg, i.p. for 7 days), METH-induced brain alterations showed a two- to fourfold increase at 21 °C, a four- to sixfold increase at 34 °C, and three- to fourfold increase at 4 °C. SiO2 exposure showed the most pronounced METH-induced brain pathology at all temperatures followed by Ag and Cu NPs. Pretreatment with a potent antioxidant compound H-290/51 (50 mg/kg, p.o., 30 min before METH) significantly reduced brain pathology in naive animals exposed to METH at 21 and 34 °C. In NPs-treated animals, however, attenuation of METH-induced brain pathology occurred only after repeated exposure of H-290/51 (-30 min, 0 min, and +30 min). These observations are the first to show that NPs exacerbate METH-induced brain pathology in both cold and hot environments and demonstrate that timely intervention with antioxidant H-290/51 could have neuroprotective effects.
    Molecular Neurobiology 06/2015; DOI:10.1007/s12035-015-9252-9 · 5.29 Impact Factor
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    ABSTRACT: Cerebrolysin is a peptide mixture able to ameliorate symptomatology and delay progression of neurological disorders such as Alzheimer's disease and dementia. The administration of this drug in humans presents several criticisms due to its short half-life, poor stability, and high doses needed to achieve the effect. This paper investigates the potential of polylactic-co-glycolide (PLGA) nanoparticles (NPs) as sustained release systems for iv administration of cerebrolysin in normal and brain injured rats. NPs were prepared by water-in-oil-in-water (w/o/w) double emulsion technique and characterized by light scattering for mean size and zeta potential and by scanning electron microscopy (SEM) for surface morphology. The NPs produced by double sonication under cooling at 60 W for 45 s, 12 mL of 1 % w:v of PVA, and 1:0.6 w:w drug/PLGA ratio (C-NPs4) displayed an adequate loading of drug (24 ± 1 mg/100 mg of NPs), zeta potential value (-13 mV), and average diameters (ranged from 250 to 330 nm) suitable to iv administration. SEM images suggested that cerebrolysin was molecularly dispersed into matricial systems and partially adhered to the NP surface. A biphasic release with an initial burst effect followed by sustained release over 24 h was observed. Long-term stability both at room and at low temperature of freeze-dried NPs was investigated. To gain deeper insight into NP stability after in vivo administration, the stability of the best NP formulation was also tested in serum. These PLGA NPs loaded with cerebrolysin were able to reduce brain pathology following traumatic brain injury. However, the size, the polydispersivity, and the surface properties of sample were significantly affected by the incubation time and the serum concentration.
    Molecular Neurobiology 06/2015; DOI:10.1007/s12035-015-9235-x · 5.29 Impact Factor
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    ABSTRACT: Traumatic brain injury (TBI) is a leading cause of death and disability for which there is currently no effective drug therapy available. Because drugs targeting a single TBI pathological pathway have failed to show clinical efficacy to date, pleiotropic agents with effects on multiple mechanisms of secondary brain damage could represent an effective option to improve brain recovery and clinical outcome in TBI patients. In this multicenter retrospective study, we investigated severity-related efficacy and safety of the add-on therapy with two concentrations (20 ml/day or 30 ml/day) of Cerebrolysin (EVER Neuro Pharma, Austria) in TBI patients. Adjunctive treatment with Cerrebrolysin started within 48 hours after TBI and clinical outcomes were ranked according to the Glasgow Outcome Scale and the Modified Rankin Disability Score at 10 and 30 days post-TBI. Analyses of efficacy were performed separately for subgroups of patients with mild, moderate or severe TBI according to Glasgow Coma Scale scores at admission. Compared to standard medical care alone (control group), both doses of Cerebrolysin were associated with improved clinical outcome scores at 10 days post-TBI in mild patients and at 10 and 30 days in moderate and severe cases. A dose-dependent effect of Cerebrolysin on TBI recovery was supported by the dose-related differences and the significant correlations with treatment duration observed for outcome measures. The safety and tolerability of Cerebrolysin in TBI patients was very good. In conclusion, the results of this large retrospective study revealed that early Cerebrolysin treatment is safe and is associated to improved TBI outcome.
    CNS & neurological disorders drug targets 04/2015; 14(5). DOI:10.2174/1871527314666150430162531 · 2.70 Impact Factor
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    ABSTRACT: We have shown previously that heat stroke produced by whole body hyperthermia (WBH) for 4 h at 38°C in diabetic rats exacerbates blood-brain barrier breakdown, brain edema formation and neuronal cell injury as compared to healthy animals after identical heat exposure. In this combination of diabetes and WBH, normal therapeutic measures do not induce sufficient neuroprotection. Thus, we investigated whether nanowired mesenchymal cells (MSCs) when delivered systemically may have better therapeutic effects on brain damage in diabetic rats after WBH. Diabetes induced by streptozotocin administration (75 mg/kg, i.p, daily for 3 days) in rats resulted in clinical symptoms of the disease within 4 to 6 weeks (blood glucose level 20 to 30 mmoles/l as compared to saline control groups (4 to 6 mmoles/l). When subjected to WBH, these diabetic rats showed a 4-to 6-fold exacerbation of blood-brain barrier breakdown to Evans blue and radioiodine, along with brain edema formation and neuronal cell injury. Intravenous administration of rat MSCs (1x106) to diabetic rats one week before WBH slightly reduced brain pathology, whereas TiO2 nanowired MSCs administered in an identical manner resulted in almost complete neuroprotection. On the other hand, MSCs alone significantly reduced brain pathology in saline-treated rats after WBH. These observations indicate that nanowired delivery of stem cells has superior therapeutic potential in heat stroke with diabetes, pointing to novel clinical perspectives in the future.
    CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 04/2015; 14(3). DOI:10.2174/1871527314666150318114335 · 2.70 Impact Factor
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    ABSTRACT: We have shown previously that heat stroke produced by whole body hyperthermia (WBH) for 4 h at 38°C in diabetic rats exacerbates blood-brain barrier breakdown, brain edema formation and neuronal cell injury as compared to healthy animals after identical heat exposure. In this combination of diabetes and WBH, normal therapeutic measures do not induce sufficient neuroprotection. Thus, we investigated whether nanowired mesenchymal cells (MSCs) when delivered systemically may have better therapeutic effects on brain damage in diabetic rats after WBH. Diabetes induced by streptozotocin administration (75 mg/kg, i.p, daily for 3 days) in rats resulted in clinical symptoms of the disease within 4 to 6 weeks (blood glucose level 20 to 30 mmoles/l as compared to saline control groups (4 to 6 mmoles/l). When subjected to WBH, these diabetic rats showed a 4-to 6-fold exacerbation of blood-brain barrier breakdown to Evans blue and radioiodine, along with brain edema formation and neuronal cell injury. Intravenous administration of rat MSCs (1x106) to diabetic rats one week before WBH slightly reduced brain pathology, whereas TiO2 nanowired MSCs administered in an identical manner resulted in almost complete neuroprotection. On the other hand, MSCs alone significantly reduced brain pathology in saline-treated rats after WBH. These observations indicate that nanowired delivery of stem cells has superior therapeutic potential in heat stroke with diabetes, pointing to novel clinical perspectives in the future.
    CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 02/2015; 14(999). DOI:10.2174/1871527314666150225130829 · 2.70 Impact Factor
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    ABSTRACT: From an interdisciplinary approach, the neurosciences (NSs) represent the junction of many fields (biology, chemistry, medicine, computer science, and psychology) and aim to explore the structural and functional aspects of the nervous system. Among modern neurophysiological methods that "measure" different processes of the human brain to salience stimuli, a special place belongs to eye tracking (ET). By detecting eye position, gaze direction, sequence of eye movement and visual adaptation during cognitive activities, ET is an effective tool for experimental psychology and neurological research. It provides a quantitative and qualitative analysis of the gaze, which is very useful in understanding choice behavior and perceptual decision making. In the high tech era, ET has several applications related to the interaction between humans and computers. Herein, ET is used to evaluate the spatial orienting of attention, the performance in visual tasks, the reactions to information on websites, the customer response to advertising, and the emotional and cognitive impact of various spurs to the brain.
    Neurological Sciences 01/2015; 36(5). DOI:10.1007/s10072-015-2076-6 · 1.50 Impact Factor
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    ABSTRACT: Introduction: Neurotoxicity caused by diverse psychostimulant drugs, for example, methamphetamine, 3,4-methylenedioxy-methamphetamine, cocaine or morphine is a cause of concern to human populations especially the young generation across the world. These recreational drugs affect brain function severely leading to addiction and brain pathology. Use of psychostimulants may induce breakdown of the blood–brain barrier to serum proteins resulting in adverse brain microenvironment, edema cell injury or eventually neuronal death. Thus, there is an urgent need to find out detailed mechanisms of psychostimulants-induced neurotoxicity in vivo models for suitable therapeutic strategies to induce neuroprotection and also to help de-addiction in clinical situations.Areas covered: In this review, psychostimulants drugs-induced neurotoxicity is discussed in view of recent literature and the financial burden it may pose on our society due to rehabilitation and de-addiction. Furthermore, experimental evidences of drug-induced neuroprotection are also discussed.Expert opinion: Use of in vivo models of neurotoxicity caused by psychostimulants is discussed based on author’s own research and to find suitable drugs that could induce neuroprotection including nanodelivery. Furthermore, novel therapeutic agents for de-addiction and reducing neurotoxicity following psychostimulants administration are presented.
    Expert Opinion on Drug Metabolism &amp Toxicology 10/2014; DOI:10.1517/17425255.2014.970168 · 2.93 Impact Factor
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    ABSTRACT: Abstract: Glatiramer acetate (GA) is one of the most widely used disease-modifying drugs for the treatment of relapsingremitting multiple sclerosis; is assumed to have inductor effects on neurotrophic factor expression. One of these neurotrophic factor systems is the brain-derived neurotrophic factor (BDNF)/receptor tyrosine kinase B (TrkB) pathway. Peripheral blood is thought to contain soluble BDNF, and some blood cells express TrkB. We attempted to determine whether GA treatment leads to changes in plasma BDNF levels and TrkB activation. Such a phenomenon are relapsingremitting multiple sclerosis patients is significantly reduced; GA treatment is not influencing peripheral BDNF levels, after one year of sustained therapy, not from the point of view of total free BDNF nor the phosphorylated TrkB.
    CNS & neurological disorders drug targets 06/2014; 13(4):647-651. DOI:10.2174/1871527313666140618110049 · 2.70 Impact Factor
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    ABSTRACT: Introduction: By analyzing literature data regarding glatiramer acetate in the treatment of relapsing-remitting multiple sclerosis one might find controversial data but the majority of authors state that the clinical evolution under the treatment showes a positive course. Materials and methods: Our goal was to analyze groups of patients, both non-treated and treated with the drug, for relapse rate, Kurtzke's Expanded Disability Status Scale (EDSS) score, Multiple Sclerosis Functional Composite (MSFC) score - upper limb disability, lower limb disability and cognition, and for cognitive dysfunction, using the Montreal Cognitive Assessment (MoCA) test, in order to objectively quantify the clinical impact of the drug. Results/Conclusions: Our results are in accordance with the literature for most of the investigated measures - relapse rate, EDSS, MSFC -, and furthermore suggest the possibility to use more extensively the MoCA test for evaluation of MS patients from the point of view of cognitive functions, after a much wider comparative assessment.
    Neuropsychopharmacologia Hungarica: a Magyar Pszichofarmakológiai Egyesület lapja = official journal of the Hungarian Association of Psychopharmacology 03/2014; 16(1):11-8.
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    ABSTRACT: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a hereditary nonhypertensive cause of recurrent lacunar stroke and cognitive decline associated with alopecia, spondylosis deformans, and lumbago.(1) The disease has been linked to mutations in the HTRA1 gene, encoding for serine protease HTRA1, loss of which causes dysregulation of transforming growth factor-β signaling.(2.)
    Neurology 02/2014; 82(10). DOI:10.1212/WNL.0000000000000202 · 8.30 Impact Factor
  • Hari Sharma, Dafin F Muresanu, Aruna Sharma
    CNS & neurological disorders drug targets 02/2014; 13(1):2-3. DOI:10.2174/187152731301140210114550 · 2.70 Impact Factor
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    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.
    Journal of Nanoscience and Nanotechnology 01/2014; 14(1):577-95. DOI:10.1166/jnn.2014.9213 · 1.34 Impact Factor
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    ABSTRACT: An efficacy population of 245 patients with vertigo of peripheral vestibular origin was recruited in Romania as part of a 3-month multinational, post-marketing surveillance study of open-label betahistine 48 mg/day (OSVaLD). Endpoints were changes in the Dizziness Handicap Index (primary endpoint), Medical Outcome Study Short-Form 36 (SF-36v2(®)), and the Hospital Anxiety and Depression Scale. During treatment, the total Dizziness Handicap Index score improved by 41 points (on a 100-point scale). Statistically significant improvements of 12-14 points were recorded in all three domains of the Dizziness Handicap Index scale (P<0.0001). Betahistine therapy was also accompanied by progressive improvements in mean Hospital Anxiety and Depression anxiety and depression scores (P<0.0001) and significant improvements in both the physical and mental component summary of the SF-36v2 (P<0.0001). Betahistine was well tolerated, with only one suspected adverse drug reaction recorded in the Romanian safety population (n=259). Betahistine 48 mg/day was associated with improvements in multiple measures of health-related quality of life and had a good tolerability profile in these Romanian patients with recurrent peripheral vestibular vertigo.
    International Journal of General Medicine 01/2014; 7:531-8. DOI:10.2147/IJGM.S71015
  • Hari S Sharma, Dafin F Muresanu, Aruna Sharma
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    ABSTRACT: The 10th Global College of Neuroprotection and Neuroregeneration Annual Conference in collaboration with the 6th International Association of Neurorestoratology VI Intercontinental Hotel, Bucharest, Romania, 4-7 April 2013 The 10th Global College of Neuroproetction and Neuroregeneration Annual Conference together with the International Association of Neurorestoratology VI was held in Bucharest under the auspicious of the Society for the Study of Neuroprotection and Neuroplasticity during 4-7 April 2013. The focus of these unified societies meeting was on neurorestoration, neuroprotection and neuroregeneration in various clinical neurodegenerative diseases; for example, Alzheimer's, Parkinson's, Huntington's disease, stroke and brain or spinal cord injuries. The main aim to enhance healthcare was suggested by the use of stem cells, nanodrug delivery of drugs and stem cells, use of multimodal drugs as well as a combination of different approaches. The meeting was attended by more than 500 delegates including researches, policy makers and healthcare professionals along with several representatives from drug industries from Europe and USA. It appears that future of neuroprotection could be achieved by the use of stem cells and nanodrug delivery in chronic neurological disorders.
    Expert Review of Neurotherapeutics 10/2013; DOI:10.1586/14737175.2013.836297 · 2.83 Impact Factor
  • Journal of the Neurological Sciences 10/2013; 333:e301. DOI:10.1016/j.jns.2013.07.1131 · 2.26 Impact Factor
  • Journal of the Neurological Sciences 10/2013; 333:e155. DOI:10.1016/j.jns.2013.07.653 · 2.26 Impact Factor
  • H.S. Sharma, D.F. Muresanu, A. Sharma
    Journal of the Neurological Sciences 10/2013; 333:e164. DOI:10.1016/j.jns.2013.07.685 · 2.26 Impact Factor
  • Journal of the Neurological Sciences 10/2013; 333:e154. DOI:10.1016/j.jns.2013.07.652 · 2.26 Impact Factor
  • Journal of the Neurological Sciences 10/2013; 333:e163. DOI:10.1016/j.jns.2013.07.680 · 2.26 Impact Factor

Publication Stats

361 Citations
148.43 Total Impact Points

Institutions

  • 2011–2014
    • Universitatea de Medicina si Farmacie Craiova
      Croiova, Dolj, Romania
  • 2009–2014
    • Iuliu Haţieganu University of Medicine and Pharmacy
      • • Division of Neurosciences
      • • Department of Urology
      Klausenburg, Cluj, Romania
  • 2012
    • Uppsala University
      • Department of Surgical Sciences
      Uppsala, Uppsala, Sweden
  • 2011–2012
    • Banaras Hindu University
      • School of Bio-Medical Engineering
      Vārānasi, Uttar Pradesh, India
  • 2007–2012
    • Universitatea Tehnica Cluj-Napoca
      Klausenburg, Cluj, Romania