Dafin F Muresanu

Uppsala University Hospital, Uppsala, Uppsala, Sweden

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Publications (86)148.73 Total impact

  • [Show abstract] [Hide abstract]
    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; · 2.94 Impact Factor
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    ABSTRACT: Cerebrolysin (CBL) is a neuroprotective agent in central nervous system (CNS) injury and stimulates neurorepair processes. Several studies in our laboratory suggest that CBL administered through nanowired technology may have superior neuroprotective efficacy in CNS trauma. In this investigation, we compared the neuroprotective efficacy of poly-lactide-co-glycolide nanoparticles (NPs) loaded with CBL vs. unloaded CBL in a rat model of concussive head injury (CHI). Free CBL or CBL loaded NPs was administered 1 h after CHI and animals sacrificed 4 h later. Changes in blood-brain barrier and brain edema formation were measured as parameters of neuroprotection in CHI after giving CBL alone or as the nanodelivered compound. Our results clearly show that delivery of CBL by NPs has superior neuroprotective effects following CHI as compared to normal CBL. This suggests that CBL delivered by NPs could have robust neuroprotective action in CNS trauma. These findings have potential clinical relevance with regard to nanodelivery of CBL, a feature that requires further investigation.
    CNS & neurological disorders drug targets. 08/2014;
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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. · 3.57 Impact Factor
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    ABSTRACT: Cognitive abilities depend primarily on cerebrovascular health and aging. In this work, we examine the pathogenic mechanisms of brain dysfunction linked to vascular risk factors, insulin signaling and cerebrovascular damage and explore how these mechanisms interfere with neurodegeneration. Although Abeta hypothesis prevails in the ethiology of Alzheimer's Disease(AD), it has become increasingly evident that disturbances in cerebral glucose metabolism is an invariant pathophysiological feature of AD and may provide an ubiquituos mechanism underlying the pathogenesis of AD. Currently, it is difficult to identify efficient therapeutic approach for brain protection and recovery, especially because we do not fully understand the underlying neurobiological processes, the nature of the pathophysiological mechanisms and the links between these two categories. Endogenous neurobiological processes, such as "brain reserves", neurotrophicity, neuroplasticity and neurogenesis, are central to protection and recovery and represent the background of endogenous defense activity (EDA).The historical concept of neuroprotection being the suppression of pathophysiological processes by a single mechanism or molecule may have been effective in clinical practice, but is now obsolete and indicates a failure of the reductionist approach to neuroprotection in the clinical setting. Pharmacological intervention should address modulation not suppression. The more pathophysiological processes are modulated, the better the chances are for therapeutic success in brain protection and recovery. Therefore, drugs with pleiotropic neuroprotective mechanisms of action are the best candidates for acute neuroprotection.
    Current neurovascular research 04/2014; · 3.23 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.
  • Hari Sharma, Dafin F Muresanu, Aruna Sharma
    CNS & neurological disorders drug targets 02/2014; 13(1):2-3. · 3.57 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. · 1.15 Impact Factor
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    ABSTRACT: To a great extent, cognitive health depends on cerebrovascular health and a deeper understanding of the subtle interactions between cerebrovascular function and cognition is needed to protect humans from one of the most devastating affliction, dementia. However, the underlying biological mechanisms are still not completely clear. Many studies demonstrated that the neurovascular unit is compromised in cerebrovascular diseases and also in other types of dementia. The hemodynamic neurovascular coupling ensures a strong increase of the cerebral blood flow (CBF) and an acute increase in neuronal glucose uptake upon increased neural activity. Dysfunction of cerebral autoregulation with increasing age along with age-related structural and functional alterations in cerebral blood vessels including accumulation of amyloid-beta (Aβ) in the media of cortical arterioles, neurovascular uncoupling due to astrocyte endfeet retraction, impairs the CBF and increases the neuronal degeneration and susceptibility to hypoxia and ischemia. A decreased cerebral glucose metabolism is an early event in Alzheimer's disease (AD) pathology and may precede the neuropathological Aβ deposition associated with AD. Aβ accumulation in turn leads to further decreases in the CBF closing the vicious cycle. Alzheimer, aging and diabetes are also influenced by insulin/insulin-like growth factor-1 signaling, and accumulated evidence indicates sporadic AD is associated with disturbed brain insulin metabolism. Understanding how vascular and metabolic factors interfere with progressive loss of functional neuronal networks becomes essential to develop efficient drugs to prevent cognitive decline in elderly.
    Journal of Neural Transmission 12/2013; · 3.05 Impact Factor
  • 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; · 2.96 Impact Factor
  • L Perju-Dumbravă, M L Muntean, D F Mureşanu
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    ABSTRACT: Introduction. Parkinson's disease (PD) is one of the most common neurodegenerative diseases, and PD patients can present a variety of comorbidities that increase with age. Among them, cardiovascular and cerebrovascular diseases are the most prominent. Aim: To assess the cardiovascular and cerebrovascular profiles of PD patients. Patients and Methods. The cardiovascular risk factors of 126 PD patients were assessed according to laboratory tests (fasting blood sugar, serum cholesterol, triglycerides, and total lipids), Doppler ultrasound examinations and personal histories of cerebrovascular disease (ischemic/hemorrhagic), cardiovascular disease (myocardial infarct or angina confirmed by electrocardiogram), hypertension and diabetes. All patients underwent cerebral structural imaging procedures: computed tomography or magnetic resonance imaging. Results. 58.73% of the patients presented with hypertension, with a slight predominance of female patients (65.38% vs. 47.92%, P = 0.05). Carotid or vertebral atheromatosis was present in 39 (30.95%) and 28 (22.22%) of patients, respectively, and was statistically correlated with the presence of ischemic lesions on cerebral imaging. Regarding the computed tomography findings, 33 patients (28.21%) presented with cortical atrophy that was not correlated with any of the investigated cardiovascular factors. Conclusions. Our findings indicate that risk factors for cardiovascular and cerebrovascular diseases are common in PD patients, possibly due to their older age. The presence of atherosclerosis and its complications can be detected in cerebral imaging studies.
    CNS & neurological disorders drug targets 08/2013; · 3.57 Impact Factor
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    ABSTRACT: This investigation examines the possibility that exposure to silica dust of hypertensive individuals may exacerbate brain pathology and sensory motor dysfunction at high environmental temperature. Hypertension was produced in rats (200-250 g) by two-kidney one clip (2K1C) method, and in these animals, SiO2 nanoparticles (NPs; 50 to 60 nm) were administered at 50 mg/kg, i.p. daily for 1 week. On the 8th day, these rats were subjected to partial restraint in a Perspex box for 4 h either at room temperature (21 °C) or at 33 °C in a biological oxygen demand incubator (wind velocity, 2.6 cm/s; relative humidity, 65 to 67 %). In these animals, behavioral functions, blood-brain barrier (BBB) permeability to Evans blue albumin (EBA) and radioiodine (([131]-)Iodine), brain water content and neuronal injuries were determined. Hypertensive rats subjected to 4 h restraint at room temperature did not exhibit BBB dysfunction, brain edema, neural injury, or alterations in rotarod or inclined plane angle performances. However, when these hypertensive rats were subjected to restraint at 33 °C, breakdown of the cortical BBB (EBA, +38 %; radioiodine, +56 %), brain water (+0.88 %), neuronal damages (+18 %), and behavioral impairment were exacerbated. Interestingly, SiO2 exposure to these rats further exacerbated BBB breakdown (EBA, 280 %; radioiodine, 350 %), brain edema (4 %), and neural injury (30 %) after identical restraint depending on the ambient temperature. SiO2 treatment also induced brain pathology and alteration in behavioral functions in normotensive rats after restraint at high temperature. These observations clearly show that hypertension significantly enhances restraint-induced brain pathology, and behavioral anomalies particularly at high ambient temperature and SiO2 intoxication further exacerbated these brain pathologies and cognitive dysfunctions.
    Molecular Neurobiology 07/2013; · 5.47 Impact Factor
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    ABSTRACT: Earlier we showed that chronic administration of engineered nanoparticles (NPs) from metals, e.g., Cu, Ag, or Al (50-60 nm, 50 mg/kg, i.p. daily for 1 week) alter blood-brain barrier (BBB) disruption and induce brain pathology in adult rats (age 18 to 22 weeks). However, effects of size-dependent neurotoxicity of NPs in vivo are still largely unknown. In present investigation, we examined the effects of different size ranges of the above-engineered NPs on brain pathology in rats. Furthermore, the fact that age is also an important factor in brain pathology was also investigated in our rat model. Our results showed that small-sized NPs induced the most pronounced BBB breakdown (EBA +480 to 680 %; radioiodine +850 to 1025 %), brain edema formation (+4 to 6 %) and neuronal injuries (+30 to 40 %), glial fibrillary acidic protein upregulation (+40 to 56 % increase), and myelin vesiculation (+30 to 35 % damage) in young animals as compared to controls. Interestingly, the oldest animals (30 to 35 weeks of age) also showed massive brain pathology as compared to young adults (18 to 20 weeks old). The Ag and Cu exhibited greater brain damage compared with Al NPs in all age groups regardless of their size. This suggests that apart from the size, the composition of NPs is also important in neurotoxicity. The very young and elderly age groups exhibited greater neurotoxicity to NPs suggests that children and elderly are more vulnerable to NPs-induced brain damage. The NPs-induced brain damage correlated well with the upregulation of neuronal nitric oxide synthase activity in the brain indicating that NPs-induced neurotoxicity may be mediated via increased production of nitric oxide, not reported earlier.
    Molecular Neurobiology 07/2013; · 5.47 Impact Factor
  • CNS & neurological disorders drug targets 05/2013; · 3.57 Impact Factor
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    Neurophysiology 05/2013; · 0.38 Impact Factor
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    ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disease of the central nervous system. Although PD is commonly characterized by well-known clinical manifestations, it also involves imbalances in the cortico-subcortical excitation and inhibition processes. Functional electrical stimulation can improve the motor condition of PD patients as a supplement to levodopa therapy. In this study, clinical (using specific tests) and paraclinical (using single-pulse transcranial magnetic stimulation) examinations revealed an improvement in the motor symptoms and the bilateral activation of the primary motor areas of the upper limbs after unilateral functional electrical stimulation in PD patients.
    CNS & neurological disorders drug targets 02/2013; · 3.57 Impact Factor
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    ABSTRACT: Purpose: To describe the characteristic clinical features and ultrasound findings of the orbital vessels and of the superficial temporal and the carotid arteries, which help differentiate newly diagnosed non-arteritic anterior ischemic optic neuropathies (NA-AION) from arteritic forms (A-AION). Patients and methods: In this prospective study, 41 consecutive patients with clinical suspicion of unilateral AION were examined following a complex protocol including color Doppler imaging (CDI) of orbital vessels. Results: The final diagnoses were A-AION due to giant cell arteritis in 8 patients, and 33 patients with NA-AION. A combination of a history of amaurosis fugax before abrupt, painless, and severe vision loss in the involved eye, and a diffuse pale optic disc edema was extremely suggestive of A-AION. However, none of these symptoms were ever found in NA-AION. CDI of the orbital vessels in A-AION revealed severe diminished blood flow velocities in the posterior ciliary arteries (PCAs), especially on the affected side, and high resistance index (RI) in all retrobulbar vessels, in both orbits. In NA-AION, blood velocities and RI in PCAs were preserved. Conclusions: CDI data of retrobulbar vessels supported the evidence of involvement of the entire PCA trunck in A-AION. In contrast, impaired flow to the optic nerve head was distal to the PCAs themselves, possibly at the level of the paraoptic branches in NA-AION cases.
    American Journal of Neuroprotecion and Neuroregeneration 12/2012; 4(2):154-162.
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    ABSTRACT: Background / Purpose: To determine whether heat stress-induced brain pathology is exacerbated in hypertensive and diabetic animals in a rat model. Main conclusion: Hypertension and diabetes in combination induces 400-600% increase in brain pathology following identical heat stress in rats. In this situation cerebrolysin given in very high doses could induce neuroprotection.
    16th Congress of the European Federation of Neurological Societies 2012; 10/2012
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    ABSTRACT: Background / Purpose: Our aim was to determine whether nanoparticle intoxication could induce astrocyte activation in different brain areas in a rat model. Main conclusion: Engineered nanoparticles from metals specifically and selectively activated astrocytes in the CNS of rats in a very precise manner.
    16th Congress of the European Federation of Neurological Societies 2012; 10/2012
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    ABSTRACT: Background / Purpose: This investigation was undertaken to find out if chronic administration of engineered nanoparticles might induce brain damage depending on their sizes and/or age of the animals in a rat model. Main conclusion: Our studies show that the magnitude and intensity of the brain damage induced by nanoparticles is inversely correlated to their sizes. Furthermore, very young and old rats are more vulnerable to brain damage caused by nanoparticles, indicating that children and the elderly are susceptible to nanoparticle-induced brain dysfunction.
    16th Congress of the European Federation of Neurological Societies 2012; 10/2012
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    ABSTRACT: Background / Purpose: This investigation aimed to find out whether chronic exposure to nanoparticles could induce oxidative stress in the brain. Main conclusion: Chronic exposure to nanoparticles induced marked increases in inducible and constitutive nitric oxide synthase (NOS) levels, which is an indicator of oxidative stress and induced brain damage. This effect was attenuated by pre-treatment with insulin like growth factor-1.
    16th Congress of the European Federation of Neurological Societies 2012; 10/2012

Publication Stats

324 Citations
148.73 Total Impact Points

Institutions

  • 2013
    • Uppsala University Hospital
      • Department of Surgical Sciences
      Uppsala, Uppsala, Sweden
  • 2007–2013
    • Universitatea de Medicina si Farmacie Craiova
      Croiova, Dolj, Romania
  • 2011–2012
    • Uppsala University
      • Department of Surgical Sciences
      Uppsala, Uppsala, Sweden
    • Banaras Hindu University
      • School of Bio-Medical Engineering
      Benares, Uttar Pradesh, India
    • Carol Davila University of Medicine and Pharmacy
      Bucureşti, Bucureşti, Romania
  • 2009–2012
    • Iuliu Haţieganu University of Medicine and Pharmacy
      • • Division of Neurosciences
      • • Department of Urology
      Cluj-Napoca, Judetul Cluj, Romania
  • 2002–2008
    • Universitatea Tehnica Cluj-Napoca
      Klausenburg, Cluj, Romania