Publications (14)34.56 Total impact
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Article: Protective effects of resveratrol on glutamate-induced damages in murine brain cultures.
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ABSTRACT: Resveratrol interacts with the complex III of the respiratory chain, is a radical scavenger and also suppressor of radical formation in the mitochondria. It reduces the intracellular calcium levels in pre- and postsynaptic neurons and also may inhibit the pro-apoptotic factors in glutamate overflow that occurs, e.g. in excitotoxicity. In cell cultures, glutamate overflow leads to formation of free radicals and results in apoptosis. This increase of radical concentration is enhanced by influx of cations like iron or copper ions into the cell. In present study, the beneficial action of resveratrol was investigated in glutamate-affected dissociated cultures of mice mesencephalic primary cultures. On the 10th day in vitro, 5 mM of glutamate was administered for 15 min and the cultures were further maintained in medium containing 0, 0.01, 0.1 or 1 μM of resveratrol. Resveratrol reduced glutamate-induced damages. The number of dopaminergic neurons was increased and their morphology ameliorated when resveratrol followed glutamate treatment. A significant reduction of glutamate-induced radical formation in cultures treated with resveratrol corresponded with a considerable high antioxidative potential of this stilbene determined using the DPPH assay. In addition, ICP-OES was set up to measure the tissues' copper and iron contents in organotypic cortical cultures of glutamate treated (0 or 30 μM) slices and those in which resveratrol (0, 0.01, 0.1 or 1 μM) was co-administered. Levels of copper were dose-dependently increased, and also the concentration of iron was higher in resveratrol-treated organotypic cultures. The hypothesis that resveratrol has beneficial actions against glutamate damages was verified.Acta Neurovegetativa 03/2013; · 2.73 Impact Factor -
Article: Recent advances in benefits and hazards of engineered nanoparticles.
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ABSTRACT: Over recent decades, engineered nanoparticles are increasingly produced as the result of the rapid development in nanotechnology. They are currently used in a wide range of industrial and public sectors including healthcare, agriculture, transport, energy, materials, and information and communication technologies. As the result, an increasing concern has been raised over the potential impacts of engineered nanoparticles to human health. In the light of this, it is the purpose of the present review to discuss: (1) novel properties of engineered nanoparticles particularly in biomedical sciences, (2) most recently reported adverse effects of manufactured nanoparticles on human health and (3) different aspects of toxicological risk assessment of these nanoparticles.Environmental toxicology and pharmacology. 08/2012; -
Article: Swainsonine as a lysosomal toxin affects dopaminergic neurons.
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ABSTRACT: Swainsonine (SW) is an indolizidine triol plant alkaloid isolated from the species Astragalus, colloquially termed locoweed. When chronically ingested by livestock and wildlife, symptoms include severe neuronal disturbance. Toxicity to the central and peripheral nervous system is caused by inhibition of lysosomal α-mannosidase (AMA) and accumulation of intracellular oligosaccharide. Consequently, SW has been used as a model substance in investigations of lysosomal storage diseases. Involvement of the basal ganglia has been postulated due to the neuronal symptoms of affected animals. Therefore, primary midbrain cultures from embryonic mice containing dopaminergic neurons were utilized in this study. Neural cells were exposed to SW (0.01-100 μM) for 72 h. AMA activity was 50 % inhibited at 1 μM SW. Cytotoxic changes in cultures were observed above 25 μM SW by increases in lactate dehydrogenase activity and nitric oxide content. Neurotoxicity to dopaminergic cells was visualized by tyrosine hydroxylase immunohistochemistry. Structural degeneration scored as dendritic shortening and shrinkage of cell bodies was dose-dependent and resulted in nerve loss above 25 μM. SW exposure caused progression from reversible to irreversible cytotoxicity. Partial regeneration of AMA-activity in culture was observed on removal of SW. The antioxidative vitamins ascorbic acid and tocopherol (both 100 μM) partially reversed the toxic effect on dopaminergic cells and ascorbic acid decreased AMA inhibition. Thus, neuronal midbrain cell cultures can demonstrate the neurotoxic action of SW and cytoprotective strategies may be tested at a single nerve cell level.Acta Neurovegetativa 06/2012; · 2.73 Impact Factor -
Article: Effects of cannabinoids Δ(9)-tetrahydrocannabinol, Δ(9)-tetrahydrocannabinolic acid and cannabidiol in MPP+ affected murine mesencephalic cultures.
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ABSTRACT: Cannabinoids derived from Cannabis sativa demonstrate neuroprotective properties in various cellular and animal models. Mitochondrial impairment and consecutive oxidative stress appear to be major molecular mechanisms of neurodegeneration. Therefore we studied some major cannabinoids, i.e. delta-9-tetrahydrocannabinolic acid (THCA), delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in mice mesencephalic cultures for their protective capacities against 1-methyl-4-phenyl pyridinium (MPP(+)) toxicity. MPP(+) is an established model compound in the research of parkinsonism that acts as a complex I inhibitor of the mitochondrial respiratory chain, resulting in excessive radical formation and cell degeneration. MPP(+) (10 μM) was administered for 48 h at the 9th DIV with or without concomitant cannabinoid treatment at concentrations ranging from 0.01 to 10 μM. All cannabinoids exhibited in vitro antioxidative action ranging from 669 ± 11.1 (THC), 16 ± 3.2 (THCA) to 356 ± 29.5 (CBD) μg Trolox (a vitamin E derivative)/mg substance in the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay. Cannabinoids were without effect on the morphology of dopaminergic cells stained by tyrosine hydroxylase (TH) immunoreaction. THC caused a dose-dependent increase of cell count up to 17.3% at 10 μM, whereas CBD only had an effect at highest concentrations (decrease of cell count by 10.1-20% at concentrations of 0.01-10 μM). It influenced the viability of the TH immunoreactive neurons significantly, whereas THCA exerts no influence on dopaminergic cell count. Exposure of cultures to 10 μM of MPP(+) for 48 h significantly decreased the number of TH immunoreactive neurons by 44.7%, and shrunken cell bodies and reduced neurite lengths could be observed. Concomitant treatment of cultures with cannabinoids rescued dopaminergic cells. Compared to MPP(+) treated cultures, THC counteracted toxic effects in a dose-dependent manner. THCA and CBD treatment at a concentration of 10 μM lead to significantly increased cell counts to 123% and 117%, respectively. Even though no significant preservation or recovery of neurite outgrowth to control values could be observed, our data show that cannabinoids THC and THCA protect dopaminergic neurons against MPP(+) induced cell death.Phytomedicine: international journal of phytotherapy and phytopharmacology 05/2012; 19(8-9):819-24. · 2.17 Impact Factor -
Article: Transient increase of free iron in rat livers following hemorrhagic-traumatic shock and reperfusion is independent of heme oxygenase 1 upregulation.
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ABSTRACT: Hemorrhagic-traumatic shock (HTS) followed by reperfusion induces heme oxygenase (HO) 1. Free iron (Fe2+) may cause oxidative stress, if not adequately sequestered. We aimed to characterize HO-1-mediated effects on Fe2+ levels in liver and transferrin-bound iron (TFBI) in plasma following HTS, including laparotomy, bleeding, and inadequate and adequate reperfusion. Anesthetized rats showed upregulated HO-1 mRNA at 40 min after HTS, which was followed by increased HO activity at 3 h after shock. Fe2+ levels were transiently increased at 40 min after shock, a time point when HO activity was not affected yet. Levels of plasma TFBI were higher in HTS animals, showing the highest levels at 40 min after shock, and decreased thereafter. In addition, we modulated HO activity 6 h before HTS by administering an inhibitor (zinc-protoporphyrin IX) or an activator (hemin) of HO. At 18 h after HTS in all shock groups, HO activity was increased, the highest being in the hemin-pretreated group. The zinc-protoporphyrin IX-treated HTS animals showed increased HO-1 mRNA and Fe2+ levels in the liver compared with the untreated HTS animals. Transferrin-bound iron levels were affected by pharmacological modulation before shock. All animals undergoing HTS displayed increased TFBI levels after reperfusion; however, in animals pretreated with hemin, TFBI levels increased less. Our data indicate that increase in Fe2+ levels in liver and plasma early after HTS is not mediated by HO-1 upregulation, but possibly reflects an increased mobilization from internal iron stores or increased cell damage. Thus, upregulation of HO activity by hemin does not increase Fe2+ levels following HTS and reperfusion.Shock (Augusta, Ga.) 08/2011; 36(5):501-9. · 2.87 Impact Factor -
Article: Vascular damage mediates neuronal and non-neuronal pathology following short and long-term rotenone administration in Sprague-Dawley rats.
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ABSTRACT: Even though rotenone has been used extensively in recent years to produce a model of Parkinson disease in rats, its systemic effects either on neurons apart from dopaminergic structures or non-neuronal tissues have not been elucidated well. In our present study, 30 adult Sprague-Dawley rats were divided into three even groups. A short-term rotenone-treated group received 10mg/kg b.w. rotenone daily for 7 days. The long-term rotenone-treated group received 3mg/kg b.w. rotenone daily for 30 days. The control group received vehicle only and were kept 5 rats each in parallel to both short- and long-term rotenone treated groups. It was found that short-term rotenone treatment produced marked vascular damages associated with ischemic neuronal degeneration particularly in the thalamus, cerebellum and nucleus dentatus. In long-term rotenone-treated group, vascular changes were less severe and neuronal degeneration was associated with mild microglial proliferation and astrocytosis. Non-neuronal pathology as the result of short-term rotenone exposure consisted of degeneration and necrosis of seminiferous tubular epithelia with formation of spermatide multinucleate giant cells. On the other hand, long-term rotenone treatment did not affect testicles and only caused sinusoidal dilatation in the liver, myocardial degeneration in the heart and interstitial hemorrhages in the kidneys and lungs. In conclusions, damage to blood vasculature by rotenone appeared mediating neuronal and non-neuronal pathology in Sprague-Dawley rats. This effect might provide new insights for ethiopathogenesis of neurodegenerative diseases and contributes to the understanding of hemorrhagic stroke.Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie 06/2011; · 1.43 Impact Factor -
Article: Ginsenosides and their CNS targets.
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ABSTRACT: Ginsenosides are a special group of triterpenoid saponins attributed to medical effects of ginseng. Therefore, they have been research targets over the last three decades to explain ginseng actions and a wealth of literature has been presented reporting on ginsenosides' effects on the human body. Recently, there is increasing evidence on beneficial effects of ginsenosides to the central nervous system (CNS). Using a wide range of in vitro and in vivo models, researchers have attributed these effects to specific pharmacological actions of ginsenosides on cerebral metabolism, oxidative stress and radical formation, neurotransmitter imbalance and membrane stabilizing effects, and even antiapoptotic effects. Modulating these particular mechanisms by ginsenosides has thus been reported to exert either general stimulatory effects on the brain functions or protecting the CNS against various disease conditions. In this review, we try to address the recently reported ginsenosides' actions on different CNS targets particularly those supporting possible therapeutic efficacies in CNS disorders and neurodegenerative diseases.CNS Neuroscience & Therapeutics 12/2010; 17(6):761-8. · 4.44 Impact Factor -
Article: Minocycline protects dopaminergic neurons against long-term rotenone toxicity.
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ABSTRACT: In Parkinson's disease, most of current therapies only provide symptomatic treatment and so far there is no drug which directly affects the disease process. To investigate the neuroprotective effects of minocycline against long-term rotenone toxicity in primary dopaminergic cell cultures. Embryonic mice of 14-days-old were used for preparation of primary dopaminergic cell cultures. On the 6th day in vitro, prepared cultures were treated both with minocycline alone (1, 5, 10 and 20 microM) and concomitantly with rotenone (5 and 20 nM) and minocycline. Cultures were incubated at 37 degrees C for six consecutive days. On Day in vitro culture medium was aspirated and used for measuring lactate dehydrogenase. Cultured cells were fixed in 4% paraformaldhyde and stained immunohistochemically against tyrosine hydroxylase. Treatment of cultures with 5 and 20 nM of rotenone significantly decreased the survival of tyrosine hydroxylase immunoreactive neurons by 27 and 31% and increased the release of lactate dehydrogenase into the culture medium by 31 and 236%, respectively compared to untreated controls. Minocycline (1, 5, 10 microM) significantly protected tyrosine hydroxylase immunoreactive neurons by 17, 15 and 19% and 13, 22 and 23% against 5 and 20 nM of rotenone, respectively compared to rotenone-treated cultures. Minocycline (only at 10 microM) significantly decreased the release of lactate dehydrogenase by 79% and 133% against 5 and 20 nM of rotenone, respectively. Minocycline has neuroprotective potential against the progressive loss of tyrosine hydroxylase immunoreactive neurons induced by long-term rotenone toxicity in primary dopaminergic cultures.The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 01/2010; 37(1):81-5. · 0.97 Impact Factor -
Article: Effects of epigallocatechin gallate on rotenone-injured murine brain cultures.
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ABSTRACT: Green tea polyphenol epigallocatechin-3-gallate (EGCG) is reported to have antioxidant abilities and to counteract beneficially mitochondrial impairment and oxidative stress. The present study was designed to investigate neuroprotective effects of EGCG on rotenone-treated dissociated mesencephalic cultures and organotypic striatal cultures. Rotenone is a potent inhibitor of complex I of the respiratory chain, which in vitro causes pathological and neurochemical characteristics of diseases in which mitochondrial impairment is involved, e.g., Parkinson's disease. Treatment with EGCG (0.1, 1, 10 muM) alone had no significant effects on mesencephalic cultures. In striatal slice cultures, EGCG led to a significant increase of propidium iodide (PI) uptake and 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM), but not dihydroethidium (DHE) fluorescence intensity. Rotenone (20 nM on the eighth DIV for 48 h) significantly decreased the numbers and the neurite lengths of TH ir neurons by 23 and 34% in dissociated mesencephalic cell cultures compared to untreated controls. Exposure of striatal slices to rotenone (0.5 mM for 48 h) significantly increased PI uptake, and DAF-FM and DHE fluorescence intensities by 41 and 136 and 19%, respectively, compared to controls. Against rotenone, in dissociated mesencephalic cultures, EGCG produced no significant effect on either the number or neurite lengths of THir neurons compared to rotenone-treated cultures, but EGCG significantly decreased PI uptake by 19% and DAF-FM fluorescence intensity by 19 and 58%, respectively, compared to increase in rotenone-exposed striatal slices. On the other hand, EGCG did not affect superoxide (O(2) (-)) formation as detected with DHE. These data indicate that EGCG slightly protects striatal slices by counteracting nitric oxide (NO(.)) production by rotenone. In conclusion, EGCG partially protects striatal slices but not dissociated cells against rotenone toxicity.Acta Neurovegetativa 09/2009; 117(1):5-12. · 2.73 Impact Factor -
Article: Reperfusion does not induce oxidative stress but sustained endoplasmic reticulum stress in livers of rats subjected to traumatic-hemorrhagic shock.
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ABSTRACT: Oxidative stress is believed to accompany reperfusion and to mediate dysfunction of the liver after traumatic-hemorrhagic shock (THS). Recently, endoplasmic reticulum (ER) stress has been suggested as an additional factor. This study investigated whether reperfusion after THS leads to increased oxidative and/or ER stress in the liver. In a rat model, including laparotomy, bleeding until decompensation, followed by inadequate or adequate reperfusion phase, three time points were investigated: 40 min, 3 h, and 18 h after shock. The reactive oxygen and nitrogen species and its scavenging capacity (superoxide dismutase 2), the nitrotyrosine formation in proteins, and the lipid peroxidation together with the status of endogenous antioxidants (alpha-tocopherylquinone-alpha-tocopherol ratio) were investigated as markers for oxidative or nitrosylative stress. Mitochondrial function and cytochrome P450 isoform 1A1 activity were analyzed as representatives for hepatocyte function. Activation of the inositol-requiring enzyme 1/X-box binding protein pathway and up-regulation of the 78-kDa glucose-regulated protein were recorded as ER stress markers. Plasma levels of alanine aminotransferase and Bax/Bcl-XL messenger RNA (mRNA) ratio were used as indicators for hepatocyte damage and apoptosis induction. Oxidative or nitrosylative stress markers or representatives of hepatocyte function were unchanged during and short after reperfusion (40 min, 3 h after shock). In contrast, ER stress markers were elevated and paralleled those of hepatocyte damage. Incidence for sustained ER stress and subsequent apoptosis induction were found at 18 h after shock. Thus, THS or reperfusion induces early and persistent ER stress of the liver, independent of oxidative or nitrosylative stress. Although ER stress was not associated with depressed hepatocyte function, it may act as an early trigger of protracted cell death, thereby contributing to delayed organ failure after THS.Shock (Augusta, Ga.) 07/2009; 33(3):289-98. · 2.87 Impact Factor -
Article: Rotenone damages striatal organotypic slice culture.
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ABSTRACT: Epidemiological studies suggest the involvement of pesticides in the etiology of Parkinson's disease. Exposure to rotenone results in degeneration of the nigrostriatal pathway through inhibition of complex I. Organotypic striatal slice cultures were prepared from brains of adult mice and treated with rotenone (0.01, 0.05, 0.1, and 1 mM) for 48 h. Lactate dehydrogenase activity was elevated by 167% at 1 mM of rotenone. Using fluorescent indicators, membrane damage was up to 130% as measured by propidium iodide fluorescence, and superoxide (DHE) and nitric oxide (DAF-FM) formation were increased by 195% and 774% at 1 mM of rotenone, respectively, compared to controls. The study concludes that formation of radicals mediated striatal degeneration by rotenone.Annals of the New York Academy of Sciences 01/2009; 1148:530-5. · 3.15 Impact Factor -
Article: Thymoquinone protects dopaminergic neurons against MPP+ and rotenone.
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ABSTRACT: Thymoquinone is the main active constituent of Nigella sativa seeds with antioxidant and antiinflammatory properties. In the present study, primary dopaminergic cultures from mouse mesencephala were used to investigate the neuroprotective effects of thymoquinone against MPP(+) and rotenone toxicities. MPP(+) (10 microm on day 10 in vitro (i.v.) for 48 h) significantly decreased the number of THir by 40% compared with untreated control cultures. Rotenone at both short (20 nm on day 10 i.v. for 48 h) and long-term (1 nm on day 6 i.v. for 6 consecutive days) toxicities reduced the number of THir neurons by 33% and 24%, respectively. Treatment of cultures with thymoquinone (0.01, 0.1, 1, 10 microm on day 8 i.v. for 4 days) rescued about 25% of THir neurons at concentrations of 0.1 microm and 1 microm against MPP(+)-induced cell death. Against rotenone, thymoquinone afforded significant protection in both short- and long-term models. In short-term rotenone toxicity, thymoquinone (from days 8-12 i.v.) saved about 65%, 74% and 79% of THir neurons at concentrations of 0.01, 0.1 and 1 microm, respectively, compared with cell loss induced by rotenone. In long-term rotenone toxicity, concomitant treatment of cultures with thymoquinone significantly rescued about 83-100% of THir neurons compared with rotenone-treated cultures. In conclusion, the current study presents for the first time the potential of thymoquinone to protect primary dopaminergic neurons against MPP(+) and rotenone relevant to Parkinson's disease.Phytotherapy Research 12/2008; 23(5):696-700. · 2.09 Impact Factor -
Article: A novel endotoxin-induced pathway: upregulation of heme oxygenase 1, accumulation of free iron, and free iron-mediated mitochondrial dysfunction.
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ABSTRACT: Mitochondria are involved in the development of organ failure in critical care diseases. However, the mechanisms underlying mitochondrial dysfunction are not clear yet. Inducible hemoxygenase (HO-1), a member of the heat shock protein family, is upregulated in critical care diseases and considered to confer cytoprotection against oxidative stress. However, one of the products of HO-1 is Fe2+ which multiplies the damaging potential of reactive oxygen species catalyzing Fenton reaction. The aim of this study was to clarify the relevance of free iron metabolism to the oxidative damage of the liver in endotoxic shock and its impact on mitochondrial function. Endotoxic shock in rats was induced by injection of lipopolysaccharide (LPS) at a dose of 8 mg/kg (i.v.). We observed that the pro-inflammatory cytokine TNF-alpha and the liver necrosis marker aspartate aminotransferase were increased in blood, confirming inflammatory response to LPS and damage to liver tissue, respectively. The levels of free iron in the liver were significantly increased at 4 and 8 h after onset of endotoxic shock, which did not coincide with the decrease of transferrin iron levels in the blood, but rather with expression of the inducible form of heme oxygenase (HO-1). The proteins important for sequestering free iron (ferritin) and the export of iron out of the cells (ferroportin) were downregulated facilitating the accumulation of free iron in cells. The temporarily increased concentration of free iron in the liver correlated with the temporary impairment of both mitochondrial function and tissue ATP levels. Addition of exogenous iron ions to mitochondria isolated from control animals resulted in an impairment of mitochondrial respiration similar to that observed in endotoxic shock in vivo. Our data suggest that free iron released by HO-1 causes mitochondrial dysfunction in pathological situations accompanied by endotoxic shock.Laboratory Investigation 02/2008; 88(1):70-7. · 3.64 Impact Factor -
Article: Ginsenosides Rb1 and Rg1 effects on mesencephalic dopaminergic cells stressed with glutamate.
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ABSTRACT: Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), is a well known and popular herbal medicine used worldwide. Among more than 30 ginsenosides, the active ingredients of ginseng, ginsenosides Rb1 and Rg1 are regarded as the main compounds responsible for many pharmaceutical actions of ginseng. In our study, primary cultures from embryonic mouse mesencephala were exposed to neurotoxic glutamate concentration and potential protective effects of these two ginsenosides on survival and neuritic growth of dopaminergic cells were tested. Treatment of primary mesencephalic culture with 500 microM glutamate for 15 min on the 10th day in vitro (DIV) increased the release of lactate dehydrogenase (LDH) into the culture medium, the propidium iodide (PI) uptake by cultured cells and the total number of nuclei with condensed and fragmented chromatin (apoptotic features) as evaluated with Hoechst 33342. Moreover, it extensively decreased the number of tyrosine hydroxylase immunopositive (TH+) cells and adversely affected the length and number of their neuronal processes. The toxic effect of glutamate was primarily mediated by over-activation of N-methyl-D-aspartate receptor (NMDA) as treatment of cultured cells with (+)-MK 801, an NMDA receptor antagonist, nearly abolished dopaminergic cells loss and LDH release induced by glutamate. When either ginsenoside was added alone for six consecutive days (at final concentrations 0.1, 1, 10, 20 microM), ginsenoside Rb1 (at 10 microM) significantly enhanced the survival of dopaminergic neurons compared to untreated controls. In these cultures, neurite lengths and numbers were not affected by both ginsenosides. Against glutamate exposure, ginsenosides Rb1 and Rg1 could not prevent cell death. However when pre-treating for 4 days or post-treating for 2 days following glutamate exposure, they significantly increased the numbers and lengths of neurites of surviving dopaminergic cells. Thus our study indicates that ginsenosides Rb1 and Rg1 have a partial neurotrophic and neuroprotective role in dopaminergic cell culture.Brain Research 10/2004; 1021(1):41-53. · 2.73 Impact Factor
Top co-authors
Top Journals
Institutions
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2004–2013
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University of Veterinary Medicine in Vienna
- Department of Biomedical Sciences
Vienna, Vienna, Austria
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2012
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Northwest A & F University
- College of Veterinary Medicine
Yangling, Shaanxi Sheng, China
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2008–2012
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Assiut University
- Department of Pathology
Asyūţ, Muhafazat Asyut, Egypt
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