27 results on '"Hassouna, I."'
Search Results
2. Revisiting adult neurogenesis and the role of erythropoietin for neuronal and oligodendroglial differentiation in the hippocampus
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Hassouna, I, primary, Ott, C, additional, Wüstefeld, L, additional, Offen, N, additional, Neher, R A, additional, Mitkovski, M, additional, Winkler, D, additional, Sperling, S, additional, Fries, L, additional, Goebbels, S, additional, Vreja, I C, additional, Hagemeyer, N, additional, Dittrich, M, additional, Rossetti, M F, additional, Kröhnert, K, additional, Hannke, K, additional, Boretius, S, additional, Zeug, A, additional, Höschen, C, additional, Dandekar, T, additional, Dere, E, additional, Neher, E, additional, Rizzoli, S O, additional, Nave, K-A, additional, Sirén, A-L, additional, and Ehrenreich, H, additional
- Published
- 2016
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3. Expression of constitutively active erythropoietin receptor in pyramidal neurons of cortex and hippocampus boosts higher cognitive functions in mice
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Sargin, D., El-Kordi, A., Agarwal, A., Müller, M., Wojcik, S., Hassouna, I., Sperling, S., Nave, K., and Ehrenreich, H.
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Cerebral Cortex ,Male ,Agricultural and Biological Sciences(all) ,Biochemistry, Genetics and Molecular Biology(all) ,Pyramidal Cells ,Hippocampus ,Recombinant Proteins ,Animals, Genetically Modified ,Mice ,Cognition ,lcsh:Biology (General) ,Memory ,Impulsive Behavior ,Receptors, Erythropoietin ,Animals ,Humans ,Learning ,Attention ,Social Behavior ,Erythropoietin ,lcsh:QH301-705.5 ,Research Article - Abstract
Background Erythropoietin (EPO) and its receptor (EPOR) are expressed in the developing brain and their transcription is upregulated in adult neurons and glia upon injury or neurodegeneration. We have shown neuroprotective effects and improved cognition in patients with neuropsychiatric diseases treated with EPO. However, the critical EPO targets in brain are unknown, and separation of direct and indirect effects has remained difficult, given the role of EPO in hematopoiesis and brain oxygen supply. Results Here we demonstrate that mice with transgenic expression of a constitutively active EPOR isoform (cEPOR) in pyramidal neurons of cortex and hippocampus exhibit enhancement of spatial learning, cognitive flexibility, social memory, and attentional capacities, accompanied by increased impulsivity. Superior cognitive performance is associated with augmented long-term potentiation of cEPOR expressing neurons in hippocampal slices. Conclusions Active EPOR stimulates neuronal plasticity independent of any hematopoietic effects and in addition to its neuroprotective actions. This property of EPOR signaling should be exploited for defining novel strategies to therapeutically enhance cognitive performance in disease conditions.
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- 2011
4. Increase in bax expression in substantia nigra following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment of mice
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Hassouna, I., Wickert, H., Zimmermann, M., and Gillardon, F.
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- 1996
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5. Association of inherited thrombophilia mutations and their combinations among palestinian women with unexplained recurrent miscarriage.
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Najjar AA, Hassouna I, Srour MA, Ibrahim HM, Assi RY, and Abd El Latif HM
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Background: Inherited thrombophilia (IT) has a complex pathophysiology and is associated with recurrent miscarriage (RM) by causing placental insufficiency and inhibiting fetal development. However, thrombophilia screening in unexplained RM cases is still questionable. This study aimed to investigate the association between the common eight IT mutations and their combinations among Palestinian women with unexplained RM., Methods: This is an unmatched case-control study with 200 women (100 unexplained RM cases, 100 controls). Eight common IT mutations namely Factor V Leiden (FVL), prothrombin gene (FII) G202120A, Methylenetetrahydrofolate Reductase (MTHFR) gene (C677T and A1298C), B-fibrinogen gene - 455G > A, FV HR2 A4070G, Plasminogen activator inhibitor 1 (PAI1) 5G/4G and Factor XIIIA (FXIIIA) V34L; were analyzed. The first five mutations were analyzed by Restriction Fragment Length Polymorphism PCR and the other three mutations were analyzed using Amplification Refractory Mutation System PCR., Results: The prevalence of the eight IT mutations among the control group was in the order PAI1 5G/4G (69%), MTHFR C677T (53%) and A1298C (47%), BFG - 455G > A (35%), FVL and FV HR2 (each 18%), FXIIIA V34L (16%) and FII G20210A (3%). Patients had a higher percentage of MTHFR A1298C (heterozygotes and mutant homozygote) compared to controls (p = 0.016). Frequencies of mutant alleles MTHFR A1298C (p < 0.001) and FXIIIA V34L (p = 0.009) were higher among patients compared to controls. No significant differences were observed for all other mutations or mutant alleles. Most patients (75%) and controls (75%) have 2-4 mutant alleles out of 8 mutant alleles studied, while 1% of patients and 2% of controls have zero mutant alleles. None of the combinations of the most often studied mutations (FVL, FII G20210A, MTHFR C1677T, and MTHFR A1298C) showed a significant difference between patients and controls., Conclusions: There was a significant association between unexplained RM and the mutant alleles of MTHFR A1298C and FXIIIA V34L. No significant association was observed between unexplained RM and the combination of both mutant alleles for the mutations studied. This study is the first Palestinian report that evaluates eight inherited thrombophilia mutations and their alleles' combinations in unexplained RM cases., (© 2024. The Author(s).)
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- 2024
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6. Evaluation of platelet parameters, coagulation markers, antiphospholipid syndrome, and thyroid function in palestinian women with recurrent pregnancy loss.
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Najjar AA, Hassouna I, Srour MA, Ibrahim HM, Assi RY, and Abd El Latif HM
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- Pregnancy, Female, Humans, Male, Aged, Young Adult, Adult, Lupus Coagulation Inhibitor, Case-Control Studies, Antibodies, Antinuclear, Arabs, Antibodies, Antiphospholipid, Glycoproteins, Immunoglobulin G, Immunoglobulin M, Antiphospholipid Syndrome complications, Abortion, Habitual etiology
- Abstract
Background: Multiple etiologies contribute to recurrent pregnancy loss (RPL) including immunological, endocrine, anatomical, genetic and infection but more than 50% of cases remain unexplained. Evidences of thrombotic and inflammatory processes were observed at maternal-fetal interface and considered pathological findings in most RPL cases including unexplained cases. This study aimed to evaluate the association between RPL and several risk factors: platelet parameters, coagulation factors, antiphospholipid syndrome, and thyroid function., Methods: This is an unmatched case-control study that included 100 RPL and 100 control women. Anthropometric and health data were collected and a gynecologist examined participants to assure fitting the inclusion criteria. Platelet parameters [including Mean Platelet Mass (MPM), Concentration (MPC) and Volume (MPV)] and ratios (MPV/Platelet, MPC/Platelet, MPM/Platelet, Platelet/Mononuclear cells), coagulation markers [Protein C (PC), Protein S (PS), Antithrombin III, D-dimer], antiphospholipid antibodies [Anti-phospholipid (APA), Anti-cardiolipin (ACA) and anti-B2-glycoprotein 1], Lupus anticoagulant, Antinuclear antibodies, and thyroid function (Thyroid stimulating hormone and anti-thyroid peroxidase) were measured., Results: Mean ages of cases and controls at marriage were 22.5 years for both, and their current ages were 29.4 and 33.0, respectively. 92% of cases and 99% of controls aged blow 30 years at marriage. 75% of cases have 3-4 miscarriages and 9% have ≥ 7 miscarriages. Our results indicated significantly lower male/female age ratio (p = .019), PC (p = .036) and PS (p = .025) in cases compared to controls. Plasma D-dimer (p = .020) and antiphospholipid antibodies [ACA (IgM and IgG), APA (IgM)] were significantly higher in cases compared to controls. No significant differences were observed between cases and controls concerning APA (IgG), anti-B2-glycoprotein 1 (IgM and IgG), Lupus anticoagulant, Antinuclear antibodies, platelet parameters, thyroid markers, family history of miscarriage, consanguineous marriage, and other health data., Conclusions: This is the first study that investigated the association between platelet, coagulation, antiphospholipid, autoimmune and thyroid parameters, and RPL in Palestinian women. Significant associations between male/female age ratio, PC, PS, D-dimer, ACA (IgM, IgG), APA (IgM) and RPL were observed. These markers could be used in evaluating RPL. These findings confirm the heterogeneous nature of RPL and emphasize the need for further studies to find out risk factors for RPL., (© 2023. The Author(s).)
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- 2023
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7. Ketogenic diet uncovers differential metabolic plasticity of brain cells.
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Düking T, Spieth L, Berghoff SA, Piepkorn L, Schmidke AM, Mitkovski M, Kannaiyan N, Hosang L, Scholz P, Shaib AH, Schneider LV, Hesse D, Ruhwedel T, Sun T, Linhoff L, Trevisiol A, Köhler S, Pastor AM, Misgeld T, Sereda M, Hassouna I, Rossner MJ, Odoardi F, Ischebeck T, de Hoz L, Hirrlinger J, Jahn O, and Saher G
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- Animals, Carbohydrates, Ketone Bodies metabolism, Mice, Proteome metabolism, Brain metabolism, Diet, Ketogenic
- Abstract
To maintain homeostasis, the body, including the brain, reprograms its metabolism in response to altered nutrition or disease. However, the consequences of these challenges for the energy metabolism of the different brain cell types remain unknown. Here, we generated a proteome atlas of the major central nervous system (CNS) cell types from young and adult mice, after feeding the therapeutically relevant low-carbohydrate, high-fat ketogenic diet (KD) and during neuroinflammation. Under steady-state conditions, CNS cell types prefer distinct modes of energy metabolism. Unexpectedly, the comparison with KD revealed distinct cell type-specific strategies to manage the altered availability of energy metabolites. Astrocytes and neurons but not oligodendrocytes demonstrated metabolic plasticity. Moreover, inflammatory demyelinating disease changed the neuronal metabolic signature in a similar direction as KD. Together, these findings highlight the importance of the metabolic cross-talk between CNS cells and between the periphery and the brain to manage altered nutrition and neurological disease.
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- 2022
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8. Brain erythropoietin fine-tunes a counterbalance between neurodifferentiation and microglia in the adult hippocampus.
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Fernandez Garcia-Agudo L, Steixner-Kumar AA, Curto Y, Barnkothe N, Hassouna I, Jähne S, Butt UJ, Grewe K, Weber MS, Green K, Rizzoli S, Nacher J, Nave KA, and Ehrenreich H
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- Animals, Cell Differentiation genetics, Hypoxia, Brain drug therapy, Mice, Mice, Transgenic, Cell Differentiation drug effects, Erythropoietin pharmacology, Hippocampus metabolism, Hypoxia, Brain metabolism, Microglia metabolism, Neurogenesis drug effects, Pyramidal Cells metabolism
- Abstract
In adult cornu ammonis hippocampi, erythropoietin (EPO) expression drives the differentiation of new neurons, independent of DNA synthesis, and increases dendritic spine density. This substantial brain hardware upgrade is part of a regulatory circle: during motor-cognitive challenge, neurons experience "functional" hypoxia, triggering neuronal EPO production, which in turn promotes improved performance. Here, we show an unexpected involvement of resident microglia. During EPO upregulation and stimulated neurodifferentiation, either by functional or inspiratory hypoxia, microglia numbers decrease. Treating mice with recombinant human (rh)EPO or exposure to hypoxia recapitulates these changes and reveals the involvement of neuronally expressed IL-34 and microglial CSF1R. Surprisingly, EPO affects microglia in phases, initially by inducing apoptosis, later by reducing proliferation, and overall dampens microglia activity and metabolism, as verified by selective genetic targeting of either the microglial or pyramidal neuronal EPO receptor. We suggest that during accelerating neuronal differentiation, EPO acts as regulator of the CSF1R-dependent microglia., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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9. Hippocampal neurons respond to brain activity with functional hypoxia.
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Butt UJ, Steixner-Kumar AA, Depp C, Sun T, Hassouna I, Wüstefeld L, Arinrad S, Zillmann MR, Schopf N, Fernandez Garcia-Agudo L, Mohrmann L, Bode U, Ronnenberg A, Hindermann M, Goebbels S, Bonn S, Katschinski DM, Miskowiak KW, Nave KA, and Ehrenreich H
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- Animals, Brain, Hippocampus, Humans, Mice, Neuronal Plasticity, Hypoxia, Neurons
- Abstract
Physical activity and cognitive challenge are established non-invasive methods to induce comprehensive brain activation and thereby improve global brain function including mood and emotional well-being in healthy subjects and in patients. However, the mechanisms underlying this experimental and clinical observation and broadly exploited therapeutic tool are still widely obscure. Here we show in the behaving brain that physiological (endogenous) hypoxia is likely a respective lead mechanism, regulating hippocampal plasticity via adaptive gene expression. A refined transgenic approach in mice, utilizing the oxygen-dependent degradation (ODD) domain of HIF-1α fused to CreERT2 recombinase, allows us to demonstrate hypoxic cells in the performing brain under normoxia and motor-cognitive challenge, and spatially map them by light-sheet microscopy, all in comparison to inspiratory hypoxia as strong positive control. We report that a complex motor-cognitive challenge causes hypoxia across essentially all brain areas, with hypoxic neurons particularly abundant in the hippocampus. These data suggest an intriguing model of neuroplasticity, in which a specific task-associated neuronal activity triggers mild hypoxia as a local neuron-specific as well as a brain-wide response, comprising indirectly activated neurons and non-neuronal cells., (© 2021. The Author(s).)
- Published
- 2021
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10. CaMKIIα Expressing Neurons to Report Activity-Related Endogenous Hypoxia upon Motor-Cognitive Challenge.
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Butt UJ, Hassouna I, Fernandez Garcia-Agudo L, Steixner-Kumar AA, Depp C, Barnkothe N, Zillmann MR, Ronnenberg A, Bonet V, Goebbels S, Nave KA, and Ehrenreich H
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- Animals, Brain physiology, Calcium-Calmodulin-Dependent Protein Kinase Type 2 metabolism, Cell Hypoxia drug effects, Cells, Cultured, Computational Biology, Dose-Response Relationship, Drug, Doublecortin Protein, Fluorescent Antibody Technique, Gene Expression Profiling, Genes, Reporter, Immunohistochemistry, Mice, Mice, Transgenic, Neurons drug effects, Pyramidal Cells metabolism, Tamoxifen pharmacology, Transcriptome, Calcium-Calmodulin-Dependent Protein Kinase Type 2 genetics, Cognition, Gene Expression, Hypoxia genetics, Hypoxia metabolism, Neurons metabolism
- Abstract
We previously introduced the brain erythropoietin (EPO) circle as a model to explain the adaptive 'brain hardware upgrade' and enhanced performance. In this fundamental circle, brain cells, challenged by motor-cognitive tasks, experience functional hypoxia, triggering the expression of EPO among other genes. We attested hypoxic cells by a transgenic reporter approach under the ubiquitous CAG promoter, with Hif-1α oxygen-dependent degradation-domain (ODD) fused to CreERT2-recombinase. To specifically focus on the functional hypoxia of excitatory pyramidal neurons, here, we generated CaMKIIα-CreERT2-ODD::R26R-tdTomato mice. Behavioral challenges, light-sheet microscopy, immunohistochemistry, single-cell mRNA-seq, and neuronal cultures under normoxia or hypoxia served to portray these mice. Upon complex running wheel performance as the motor-cognitive task, a distinct increase in functional hypoxic neurons was assessed immunohistochemically and confirmed three-dimensionally. In contrast, fear conditioning as hippocampal stimulus was likely too short-lived to provoke neuronal hypoxia. Transcriptome data of hippocampus under normoxia versus inspiratory hypoxia revealed increases in CA1 CaMKIIα-neurons with an immature signature, characterized by the expression of Dcx, Tbr1, CaMKII α, Tle4 , and Zbtb20 , and consistent with accelerated differentiation. The hypoxia reporter response was reproduced in vitro upon neuronal maturation. To conclude, task-associated activity triggers neuronal functional hypoxia as a local and brain-wide reaction mediating adaptive neuroplasticity. Hypoxia-induced genes such as EPO drive neuronal differentiation, brain maturation, and improved performance.
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- 2021
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11. Transplacental neurotoxicity of cypermethrin induced astrogliosis, microgliosis and depletion of let-7 miRNAs expression in the developing rat cerebral cortex.
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Hassouna I
- Abstract
The use of type II pyrethroids, cypermethrin is becoming a growing concern among environmental research centers. While most studies have attempted to cover the areas of DNA damage and microglia activation following exposure to cypermethin in the adult or postnatal life, less is known about the exact degree of neurotoxicity that results from exposure to transplacental sublethal doses of cypermethrin. To study the transplacental neurotoxicity of cypermethrin, pregnant rats were orally administered 10 % of LD
50 (25 mg/kg body weight) cypermethrin, one dose daily for one week during the gestational days 15-21. The pups were investigated at postnatal day7, 14 and 21 after birth. In brain, DNA alterations were detected, astrocytes and microglia quantification were performed and some let7 family member miRNAs are estimated. The results show a gain of three major bands in the range of 350bp to 2100bp with high intensities in cortex exposed to cypermethrin compared with similar pattern indicating unaffected genomic regions in thalamus and hypothalamus at 21days. Moreover, increases in the percentage of GFAP positive astrocytes and IBA1 positive microglia indicate astrogliosis and microgliosis respectively due to cypermethrin treatment in cerebral cortex. For the first time, drastically reduced expression of let7a, b and c members are also associated with gliosis and DNA alterations, which are detected in cerebral cortex, following transplacental neurotoxicity of cypermethrin. Taking together, these results suggest that cypermethrin neurotoxicity may be mediated partly through let7 miRNAs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author.)- Published
- 2020
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12. Functional hypoxia drives neuroplasticity and neurogenesis via brain erythropoietin.
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Wakhloo D, Scharkowski F, Curto Y, Javed Butt U, Bansal V, Steixner-Kumar AA, Wüstefeld L, Rajput A, Arinrad S, Zillmann MR, Seelbach A, Hassouna I, Schneider K, Qadir Ibrahim A, Werner HB, Martens H, Miskowiak K, Wojcik SM, Bonn S, Nacher J, Nave KA, and Ehrenreich H
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- Animals, Cell Differentiation drug effects, Cognition drug effects, Dendritic Spines drug effects, Dendritic Spines metabolism, Erythropoietin pharmacology, Female, Gene Deletion, Humans, Male, Mice, Inbred C57BL, Models, Neurological, Motor Activity drug effects, Physical Conditioning, Animal, Physical Endurance drug effects, Proto-Oncogene Proteins c-fos metabolism, Pyramidal Cells drug effects, Pyramidal Cells metabolism, Receptors, Erythropoietin metabolism, Transcriptome drug effects, Transcriptome genetics, Brain metabolism, Brain physiopathology, Erythropoietin metabolism, Hypoxia metabolism, Hypoxia physiopathology, Neurogenesis drug effects, Neuronal Plasticity drug effects
- Abstract
Erythropoietin (EPO), named after its role in hematopoiesis, is also expressed in mammalian brain. In clinical settings, recombinant EPO treatment has revealed a remarkable improvement of cognition, but underlying mechanisms have remained obscure. Here, we show with a novel line of reporter mice that cognitive challenge induces local/endogenous hypoxia in hippocampal pyramidal neurons, hence enhancing expression of EPO and EPO receptor (EPOR). High-dose EPO administration, amplifying auto/paracrine EPO/EPOR signaling, prompts the emergence of new CA1 neurons and enhanced dendritic spine densities. Single-cell sequencing reveals rapid increase in newly differentiating neurons. Importantly, improved performance on complex running wheels after EPO is imitated by exposure to mild exogenous/inspiratory hypoxia. All these effects depend on neuronal expression of the Epor gene. This suggests a model of neuroplasticity in form of a fundamental regulatory circle, in which neuronal networks-challenged by cognitive tasks-drift into transient hypoxia, thereby triggering neuronal EPO/EPOR expression.
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- 2020
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13. Genetically induced brain inflammation by Cnp deletion transiently benefits from microglia depletion.
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Garcia-Agudo LF, Janova H, Sendler LE, Arinrad S, Steixner AA, Hassouna I, Balmuth E, Ronnenberg A, Schopf N, van der Flier FJ, Begemann M, Martens H, Weber MS, Boretius S, Nave KA, and Ehrenreich H
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- Adult, Animals, Brain drug effects, Female, Humans, Male, Mice, Mice, Inbred C57BL, Microglia drug effects, Organic Chemicals pharmacology, Phenotype, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor genetics, Sequence Deletion drug effects, 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase genetics, Brain pathology, Encephalitis genetics, Microglia pathology, Sequence Deletion genetics
- Abstract
Reduced expression of 2'-3'-cyclic nucleotide 3'-phosphodiesterase ( Cnp ) in humans and mice causes white matter inflammation and catatonic signs. These consequences are experimentally alleviated by microglia ablation via colony-stimulating factor 1 receptor (CSF1R) inhibition using PLX5622. Here we address for the first time preclinical topics crucial for translation, most importantly 1 ) the comparison of 2 long-term PLX5622 applications (prevention and treatment) vs. 1 treatment alone, 2 ) the correlation of catatonic signs and executive dysfunction, 3 ) the phenotype of leftover microglia evading depletion, and 4 ) the role of intercellular interactions for efficient CSF1R inhibition. Based on our Cnp
-/- mouse model and in vitro time-lapse imaging, we report the unexpected discovery that microglia surviving under PLX5622 display a highly inflammatory phenotype including aggressive premortal phagocytosis of oligodendrocyte precursor cells. Interestingly, ablating microglia in vitro requires mixed glial cultures, whereas cultured pure microglia withstand PLX5622 application. Importantly, 2 extended rounds of CSF1R inhibition are not superior to 1 treatment regarding any readout investigated (magnetic resonance imaging and magnetic resonance spectroscopy, behavior, immunohistochemistry). Catatonia-related executive dysfunction and brain atrophy of Cnp-/- mice fail to improve under PLX5622. To conclude, even though microglia depletion is temporarily beneficial and worth pursuing, complementary treatment strategies are needed for full and lasting recovery.-Fernandez Garcia-Agudo, L., Janova, H., Sendler, L. E., Arinrad, S., Steixner, A. A., Hassouna, I., Balmuth, E., Ronnenberg, A., Schopf, N., van der Flier, F. J., Begemann, M., Martens, H., Weber, M. S., Boretius, S., Nave, K.-A., Ehrenreich, H. Genetically induced brain inflammation by Cnp deletion transiently benefits from microglia depletion.- Published
- 2019
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14. Genetic polymorphisms and protein expression of P53 and BRCA1 in preneoplastic and neoplastic rat mammary glands.
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Al-Dhaheri W, Hassouna I, and Karam SM
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- 9,10-Dimethyl-1,2-benzanthracene adverse effects, Animals, BRCA1 Protein genetics, Cell Cycle, Cell Nucleus metabolism, Cytoplasm metabolism, Disease Progression, Exons, Female, Gene Expression Regulation, Neoplastic, Mammary Neoplasms, Experimental chemically induced, Mammary Neoplasms, Experimental genetics, Mammary Neoplasms, Experimental metabolism, Polymorphism, Restriction Fragment Length, Polymorphism, Single-Stranded Conformational, Precancerous Conditions genetics, Precancerous Conditions metabolism, Protein Transport, Rats, Tumor Suppressor Protein p53 metabolism, BRCA1 Protein metabolism, Genetic Variation, Mammary Neoplasms, Experimental pathology, Precancerous Conditions pathology, Tumor Suppressor Protein p53 genetics
- Abstract
Breast cancer is the most common type of cancer and the leading cause of cancer-related deaths among women in the United Arab Emirates and worldwide. Although many factors contribute to the high incidence of breast cancer, a considerable number of cases are related to environmental factors. In the present study, breast cancer was induced in female rats using a single dose, 80 mg/kg body wt, of the environmental carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). The aim of the present study, was to characterize some of the molecular changes that occur during breast cancer development in the DMBA-treated rat model. Mammary gland tissues of control and DMBA-treated rats were processed for: i) immunohistochemical probing using anti-BRCA1 antibody to characterize and correlate the localization of this cell cycle protein during progression to cancer, ii) western blotting to analyze the alteration of p53 protein expression in preneoplastic and neoplastic lesions of the mammary glands, and iii) polymerase chain reactions using primers specific for BRCA1 and P53 genes followed by single stranded conformational polymorphism (SSCP) or restriction fragment length polymorphism (RFLP) assays to detect possible mutations in these genes during development of breast cancer. Microscopic examination revealed a wide range of preneoplastic and neoplastic lesions providing a sequence representing the multistep process of breast cancer formation in DMBA-treated rats. Probing for BRCA1 protein revealed a gradual defect in its translocation from the cytoplasm to the nucleus during breast cancer progression. In control rats, BRCA1 was present in the nuclei of terminal duct epithelial cells. However, in the preneoplastic lesions, BRCA1 was localized in both the cytoplasm and nuclei of the epithelial duct cells. In all malignant lesions, BRCA1 was mostly found in the cytoplasm. Western blotting revealed initial downregulation in the expression of p53 protein during breast cancer development. However, with progression towards malignancy, upregulation of p53 was observed. These changes were associated with polymorphism in p53 gene, which was detected in exon 5 using SSCP assay. However, using RFLP and BamHI to digest the PCR products of exon 11 of BRCA1 gene revealed no detectable polymorphisms. In conclusion, molecular characterization of the early changes that occur during development of breast cancer provides some clues for better understanding of its pathogenesis.
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- 2018
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15. Cortical network dysfunction caused by a subtle defect of myelination.
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Poggi G, Boretius S, Möbius W, Moschny N, Baudewig J, Ruhwedel T, Hassouna I, Wieser GL, Werner HB, Goebbels S, Nave KA, and Ehrenreich H
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- 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase genetics, 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase metabolism, Age Factors, Animals, Disease Models, Animal, Exploratory Behavior physiology, Female, Leukoencephalopathies diagnostic imaging, Leukoencephalopathies genetics, Maze Learning physiology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microglia metabolism, Microglia pathology, Microglia ultrastructure, Myelin Basic Protein genetics, Myelin Basic Protein metabolism, Myelin Sheath genetics, Myelin Sheath ultrastructure, Neural Pathways metabolism, Neural Pathways physiopathology, Nitric Oxide Synthase Type II genetics, Nitric Oxide Synthase Type II metabolism, Pregnancy, Prepulse Inhibition genetics, Reflex, Startle genetics, White Matter ultrastructure, Leukoencephalopathies pathology, Leukoencephalopathies physiopathology, Myelin Sheath metabolism, Neural Pathways pathology, White Matter pathology
- Abstract
Subtle white matter abnormalities have emerged as a hallmark of brain alterations in magnetic resonance imaging or upon autopsy of mentally ill subjects. However, it is unknown whether such reduction of white matter and myelin contributes to any disease-relevant phenotype or simply constitutes an epiphenomenon, possibly even treatment-related. Here, we have re-analyzed Mbp heterozygous mice, the unaffected parental strain of shiverer, a classical neurological mutant. Between 2 and 20 months of age, Mbp(+/-) versus Mbp(+/+) littermates were deeply phenotyped by combining extensive behavioral/cognitive testing with MRI, 1H-MR spectroscopy, electron microscopy, and molecular techniques. Surprisingly, Mbp-dependent myelination was significantly reduced in the prefrontal cortex. We also noticed a mild but progressive hypomyelination of the prefrontal corpus callosum and low-grade inflammation. While most behavioral functions were preserved, Mbp(+/-) mice exhibited defects of sensorimotor gating, as evidenced by reduced prepulse-inhibition, and a late-onset catatonia phenotype. Thus, subtle but primary abnormalities of CNS myelin can be the cause of a persistent cortical network dysfunction including catatonia, features typical of neuropsychiatric conditions. GLIA 2016;64:2025-2040., (© 2016 The Authors. Glia Published by Wiley Periodicals, Inc.)
- Published
- 2016
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16. Selective expression of a constitutively active erythropoietin receptor in GABAergic neurons alters hippocampal network properties without affecting cognition.
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Wüstefeld L, Winkler D, Janc OA, Hassouna I, Ronnenberg A, Ostmeier K, Müller M, Brose N, Ehrenreich H, and Wojcik SM
- Abstract
We have previously shown that treatment with erythropoietin (EPO) improves cognition in patients with neuropsychiatric disorders as well as in healthy mice, and that transgenic expression of a constitutively active form of the EPO receptor (cEPOR) in glutamatergic neurons boosts higher cognitive functions in mice. In the present work, we examined whether selective activation of EPOR signaling in GABAergic neurons would also modulate cognitive performance. We generated transgenic mice that express cEPOR under the control of the vesicular inhibitory amino acid transporter (Viaat) promoter and subjected them to comprehensive behavioral, cognitive, and electrophysiological analyses. We demonstrate that transgenic expression of cEPOR in GABAergic neurons alters hippocampal gamma-oscillations and enhances long-term potentiation but neither impairs nor improves cognition. To conclude, constitutively active EPOR in GABAergic neurons changes hippocampal network properties without affecting cognition, which suggests that the effect of EPO on cognition is dominated by its effect on the glutamatergic system. Treatment with EPO improves cognitive performance. We previously demonstrated that this effect is replicated by constitutive autoactivation of cEPOR in glutamatergic neurons. By contrast, cEPOR in GABAergic neurons changes hippocampal network properties but neither impairs nor enhances cognition. Thus, EPO modulates neuronal plasticity, and the cognitive benefits may be mainly attributable to its effect on the glutamatergic system., (© 2015 International Society for Neurochemistry.)
- Published
- 2016
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17. Widespread Expression of Erythropoietin Receptor in Brain and Its Induction by Injury.
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Ott C, Martens H, Hassouna I, Oliveira B, Erck C, Zafeiriou MP, Peteri UK, Hesse D, Gerhart S, Altas B, Kolbow T, Stadler H, Kawabe H, Zimmermann WH, Nave KA, Schulz-Schaeffer W, Jahn O, and Ehrenreich H
- Abstract
Erythropoietin (EPO) exerts potent neuroprotective, neuroregenerative and procognitive functions. However, unequivocal demonstration of erythropoietin receptor (EPOR) expression in brain cells has remained difficult since previously available anti-EPOR antibodies (EPOR-AB) were unspecific. We report here a new, highly specific, polyclonal rabbit EPOR-AB directed against different epitopes in the cytoplasmic tail of human and murine EPOR and its characterization by mass spectrometric analysis of immuno-precipitated endogenous EPOR, Western blotting, immunostaining and flow cytometry. Among others, we applied genetic strategies including overexpression, Lentivirus-mediated conditional knockout of EpoR and tagged proteins, both on cultured cells and tissue sections, as well as intracortical implantation of EPOR -transduced cells to verify specificity. We show examples of EPOR expression in neurons, oligodendroglia, astrocytes and microglia. Employing this new EPOR-AB with double-labeling strategies, we demonstrate membrane expression of EPOR as well as its localization in intracellular compartments such as the Golgi apparatus. Moreover, we show injury-induced expression of EPOR. In mice, a stereotactically applied stab wound to the motor cortex leads to distinct EpoR expression by reactive GFAP-expressing cells in the lesion vicinity. In a patient suffering from epilepsy, neurons and oligodendrocytes of the hippocampus strongly express EPOR. To conclude, this new analytical tool will allow neuroscientists to pinpoint EPOR expression in cells of the nervous system and to better understand its role in healthy conditions, including brain development, as well as under pathological circumstances, such as upregulation upon distress and injury.
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- 2015
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18. Preexisting Serum Autoantibodies Against the NMDAR Subunit NR1 Modulate Evolution of Lesion Size in Acute Ischemic Stroke.
- Author
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Zerche M, Weissenborn K, Ott C, Dere E, Asif AR, Worthmann H, Hassouna I, Rentzsch K, Tryc AB, Dahm L, Steiner J, Binder L, Wiltfang J, Sirén AL, Stöcker W, and Ehrenreich H
- Subjects
- Aged, Aged, 80 and over, Apolipoprotein E4 genetics, Blood-Brain Barrier immunology, Blood-Brain Barrier pathology, Disease Progression, Female, Heterozygote, Humans, Infarction, Middle Cerebral Artery pathology, Intracranial Hemorrhages etiology, Male, Middle Aged, Prospective Studies, Seroepidemiologic Studies, Treatment Outcome, Autoantibodies analysis, Brain Ischemia pathology, Receptors, N-Methyl-D-Aspartate immunology, Stroke pathology
- Abstract
Background and Purpose: Recently, we reported high seroprevalence (age-dependent up to >19%) of N-methyl-d-aspartate-receptor subunit NR1 (NMDAR1) autoantibodies in both healthy and neuropsychiatrically ill subjects (N=4236). Neuropsychiatric syndrome relevance was restricted to individuals with compromised blood-brain barrier, for example, apolipoprotein E4 (APOE4) carrier status, both clinically and experimentally. We now hypothesized that these autoantibodies may upon stroke be protective in individuals with hitherto intact blood-brain barrier, but harmful for subjects with chronically compromised blood-brain barrier., Methods: Of 464 patients admitted with acute ischemic stroke in the middle cerebral artery territory, blood for NMDAR1 autoantibody measurements and APOE4 carrier status as indicator of a preexisting leaky blood-brain barrier was collected within 3 to 5 hours after stroke. Evolution of lesion size (delta day 7-1) in diffusion-weighted magnetic resonance imaging was primary outcome parameter. In subgroups, NMDAR1 autoantibody measurements were repeated on days 2 and 7., Results: Of all 464 patients, 21.6% were NMDAR1 autoantibody-positive (immunoglobulin M, A, or G) and 21% were APOE4 carriers. Patients with magnetic resonance imaging data available on days 1 and 7 (N=384) were divided into 4 groups according to NMDAR1 autoantibody and APOE4 status. Groups were comparable in all stroke-relevant presenting characteristics. The autoantibody+/APOE4- group had a smaller mean delta lesion size compared with the autoantibody-/APOE4- group, suggesting a protective effect of circulating NMDAR1 autoantibodies. In contrast, the autoantibody+/APOE4+ group had the largest mean delta lesion area. NMDAR1 autoantibody serum titers dropped on day 2 and remounted by day 7., Conclusions: Dependent on blood-brain barrier integrity before an acute ischemic brain injury, preexisting NMDAR1 autoantibodies seem to be beneficial or detrimental., (© 2015 American Heart Association, Inc.)
- Published
- 2015
- Full Text
- View/download PDF
19. Simultaneous administration of hesperidin or garlic oil modulates diazinon-induced hemato- and immunotoxicity in rats.
- Author
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Hassouna I, Ibrahim H, Abdel Gaffar F, El-Elaimy I, and Abdel Latif H
- Subjects
- Animals, CD4-Positive T-Lymphocytes pathology, CD8-Positive T-Lymphocytes pathology, Male, Rats, Allyl Compounds pharmacology, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Chemical and Drug Induced Liver Injury immunology, Chemical and Drug Induced Liver Injury pathology, Chemical and Drug Induced Liver Injury prevention & control, Diazinon toxicity, Hesperidin pharmacology, Sulfides pharmacology
- Abstract
Diazinon (DZN) has been used for several years in agriculture and urban applications leading to a variety of negative effects on health. Hesperidin (HDN) and garlic oil are naturally occurring compounds present in fruits and vegetables, which have been reported to have antioxidants and anti-inflammatory actions. This study was undertaken to throw light on the modulatory effect of HDN or garlic oil against hemato- and immunotoxicity induced by DZN in Wistar rats. Oral administration of DZN for 30 days resulted in significant decrease in RBCs count, Hb content, Ht value, platelet count, and relative lymphocyte and monocyte counts when compared with control groups. Moreover, DZN reduced significantly the serum total immunoglobulin concentration, hemagglutination titer, quantitative hemolysis of SRBCs, delayed type hypersensitivity, blood mononuclear cell proliferation, phagocytic index and blood T-cell subtypes (CD4(+) and CD8(+)) in comparison with vehicle treatment. Co-administration of HDN or garlic oil, 30 min before DZN was able to normalize most of the hematological and immunological parameters. These results suggested that HDN or garlic oil, the natural antioxidants, can alleviate DZN induced hemato- and immunotoxicity.
- Published
- 2015
- Full Text
- View/download PDF
20. Uncoupling of neurodegeneration and gliosis in a murine model of juvenile cortical lesion.
- Author
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Sargin D, Hassouna I, Sperling S, Sirén AL, and Ehrenreich H
- Subjects
- Animals, Astrocytes physiology, Atrophy, Brain pathology, Brain Injuries pathology, Brain Injuries physiopathology, Brain Injuries therapy, Cold Temperature, Cyclic Nucleotide Phosphodiesterases, Type 3 metabolism, Disease Models, Animal, Erythropoietin therapeutic use, Gliosis pathology, Gliosis therapy, Glutamate Decarboxylase metabolism, Humans, Male, Mice, Mice, Inbred C57BL, Microglia physiology, Neurodegenerative Diseases pathology, Neurodegenerative Diseases therapy, Neurons physiology, Parvalbumins metabolism, Synapsins metabolism, gamma-Aminobutyric Acid metabolism, Brain physiopathology, Brain Injuries complications, Gliosis complications, Gliosis physiopathology, Neurodegenerative Diseases complications, Neurodegenerative Diseases physiopathology
- Abstract
A small experimental cryolesion to the right parietal cortex of juvenile mice causes late-onset global brain atrophy with memory impairments, reminiscent of cognitive decline, and progressive brain matter loss in schizophrenia. However, the cellular events underlying this global neurodegeneration are not understood. Here we show, based on comprehensive stereological analysis, that early unilateral lesion causes immediate and lasting bilateral increase in the number of microglia in cingulate cortex and hippocampus, consistent with a chronic low-grade inflammatory process. Whereas the total number of neurons and astrocytes in these brain regions remain unaltered, pointing to a non- gliotic neurodegeneration (as seen in schizophrenia), the subgroup of parvalbumin-positive inhibitory GABAergic interneurons is increased bilaterally in the hippocampus, as is the expression of the GABA-synthesizing enzyme GAD67. Moreover, unilateral parietal lesion causes a decrease in the expression of synapsin1, suggesting impairment of presynaptic functions/neuroplasticity. Reduced expression of the myelin protein cyclic nucleotide phosphodiesterase, reflecting a reduction of oligodendrocytes, may further contribute to the observed brain atrophy. Remarkably, early intervention with recombinant human erythropoietin (EPO), a hematopoietic growth factor with multifaceted neuroprotective properties (intraperitoneal injection of 5000 IU/kg body weight every other day for 3 weeks), prevented all these neurodegenerative changes. To conclude, unilateral parietal lesion of juvenile mice induces a non- gliotic neurodegenerative process, susceptible to early EPO treatment. Although the detailed mechanisms remain to be defined, these profound EPO effects open new ways for prophylaxis and therapy of neuropsychiatric diseases, e.g. schizophrenia.
- Published
- 2009
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- View/download PDF
21. Erythropoietin augments survival of glioma cells after radiation and temozolomide.
- Author
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Hassouna I, Sperling S, Kim E, Schulz-Schaeffer W, Rave-Fränk M, Hasselblatt M, Jelkmann W, Giese A, and Ehrenreich H
- Subjects
- Animals, Brain Neoplasms drug therapy, Brain Neoplasms pathology, Brain Neoplasms radiotherapy, Cell Line, Tumor, Cell Movement drug effects, Combined Modality Therapy, Dacarbazine therapeutic use, Gliosarcoma drug therapy, Gliosarcoma pathology, Gliosarcoma radiotherapy, Humans, Mice, Mice, Nude, Neoplasm Transplantation, Temozolomide, Transplantation, Heterologous, Antineoplastic Agents, Alkylating therapeutic use, Cell Division drug effects, Cell Survival drug effects, Dacarbazine analogs & derivatives, Erythropoietin pharmacology, Glioma drug therapy, Glioma pathology, Glioma radiotherapy
- Abstract
Purpose: Despite beneficial effects of irradiation/chemotherapy on survival of glioblastoma (GBM) patients, collateral damage to intact neural tissue leads to "radiochemobrain" and reduced quality of life in survivors. For prophylactic neuroprotection, erythropoietin (EPO) is a promising candidate, provided that concerns regarding potential tumor promoting effects are alleviated., Methods and Materials: Human GBM-derived cell lines U87, G44, G112, and the gliosarcoma-derived line G28 were treated with EPO, with and without combinations of irradiation or temozolomide (TMZ). Responsiveness of glioma cells to EPO was measured by cell migration from spheroids, cell proliferation, and clonogenic survival. Implantation of U87 cells into brains of nude mice, followed 5 days later by EPO treatment (5,000 U/kg intraperitoneal every other day for 2 weeks) should reveal effects of EPO on tumor growth in vivo. Reverse transcriptase-polymerase chain reaction was performed for EPOR, HIF-1alpha, and epidermal growth factor receptor (EGFR)vIII in cell lines and 22 human GBM specimens., Results: EPO did not modulate basal glioma cell migration and stimulated proliferation in only one of four cell lines. Importantly, EPO did not enhance tumor growth in mouse brains. Preincubation of glioma cells with EPO for 3 h, followed by irradiation and TMZ for another 24 h, resulted in protection against chemoradiation-induced cytotoxicity in three cell lines. Conversely, EPO induced a dose-dependent decrease in survival of G28 gliosarcoma cells. In GBM specimens, expression of HIF-1alpha correlated positively with expression of EPOR and EGFRvIII. EPOR and EGFRvIII expression did not correlate., Conclusions: EPO is unlikely to appreciably influence basal glioma growth. However, concomitant use of EPO with irradiation/chemotherapy in GBM patients is not advisable.
- Published
- 2008
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22. Erythropoietin enhances hippocampal long-term potentiation and memory.
- Author
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Adamcio B, Sargin D, Stradomska A, Medrihan L, Gertler C, Theis F, Zhang M, Müller M, Hassouna I, Hannke K, Sperling S, Radyushkin K, El-Kordi A, Schulze L, Ronnenberg A, Wolf F, Brose N, Rhee JS, Zhang W, and Ehrenreich H
- Subjects
- Animals, Cell Culture Techniques, Cells, Cultured, Electrophysiology, Hippocampus physiology, Immunoblotting, Long-Term Potentiation physiology, Male, Memory physiology, Mice, Microscopy, Confocal, Neuronal Plasticity drug effects, Neuronal Plasticity physiology, Neurons physiology, Reverse Transcriptase Polymerase Chain Reaction, Synapses physiology, Synaptic Transmission drug effects, Synaptic Transmission physiology, Synaptic Vesicles drug effects, Synaptic Vesicles physiology, Erythropoietin pharmacology, Hippocampus drug effects, Long-Term Potentiation drug effects, Memory drug effects
- Abstract
Background: Erythropoietin (EPO) improves cognition of human subjects in the clinical setting by as yet unknown mechanisms. We developed a mouse model of robust cognitive improvement by EPO to obtain the first clues of how EPO influences cognition, and how it may act on hippocampal neurons to modulate plasticity., Results: We show here that a 3-week treatment of young mice with EPO enhances long-term potentiation (LTP), a cellular correlate of learning processes in the CA1 region of the hippocampus. This treatment concomitantly alters short-term synaptic plasticity and synaptic transmission, shifting the balance of excitatory and inhibitory activity. These effects are accompanied by an improvement of hippocampus dependent memory, persisting for 3 weeks after termination of EPO injections, and are independent of changes in hematocrit. Networks of EPO-treated primary hippocampal neurons develop lower overall spiking activity but enhanced bursting in discrete neuronal assemblies. At the level of developing single neurons, EPO treatment reduces the typical increase in excitatory synaptic transmission without changing the number of synaptic boutons, consistent with prolonged functional silencing of synapses., Conclusion: We conclude that EPO improves hippocampus dependent memory by modulating plasticity, synaptic connectivity and activity of memory-related neuronal networks. These mechanisms of action of EPO have to be further exploited for treating neuropsychiatric diseases.
- Published
- 2008
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23. Characterization of breast cancer progression in the rat.
- Author
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Al-Dhaheri WS, Hassouna I, Al-Salam S, and Karam SM
- Subjects
- 9,10-Dimethyl-1,2-benzanthracene toxicity, Animals, Carcinogens toxicity, Disease Progression, Female, Immunohistochemistry, Mammary Neoplasms, Experimental chemically induced, Mammary Neoplasms, Experimental metabolism, Proliferating Cell Nuclear Antigen metabolism, Rats, Rats, Wistar, Mammary Neoplasms, Experimental pathology
- Abstract
The incidence of breast cancer is continuously increasing worldwide. This increasing trend is attributed partly to the fact that a considerable number of cases are related to environmental factors and partly to the little information available on the early changes that occur during mammary gland carcinogenesis. To characterize some of these early cellular changes, breast cancer was induced in female rats using a single intragastric dose of the environmental carcinogen 7,12-dimethylbenz[a]anthracene (DMBA; 80 mg/kg body weight). Mammary gland tissues of control and DMBA-treated rats were processed for routine histopathological examination and immunohistochemical analysis using an antibody specific for the proliferating cell nuclear antigen (PCNA). Microscopic examination of all mammary glands of DMBA-treated rats revealed a wide range of preneoplastic stages in addition to the well-characterized benign and malignant tumors that developed. The first stage was characterized by slightly dilated terminal ducts with accumulation of dead cells. This was designated the stage of cell death. Then, stages of hyperplasia, dysplasia, and carcinoma in situ followed. Immunohistochemical localization of PCNA in these preneoplastic lesions revealed an initial decrease followed by a gradual increase in the labeling index of PCNA. In conclusion, the DMBA-treated rats provide a useful model to dissect the early changes that occur during the multistep process of mammary gland carcinogenesis.
- Published
- 2008
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- View/download PDF
24. Systemic adverse events: a comparison between topical and peribulbar anaesthesia in cataract surgery.
- Author
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Stupp T, Hassouna I, Soppart K, Thanos S, and Förster W
- Subjects
- Administration, Topical, Adult, Age Distribution, Aged, Aged, 80 and over, Female, Humans, Incidence, Injections adverse effects, Intraoperative Complications epidemiology, Male, Middle Aged, Orbit, Retrospective Studies, Anesthesia, Local adverse effects, Anesthetics, Local administration & dosage, Cataract Extraction
- Abstract
Aims: To evaluate the safety of topical anaesthesia (TA) versus peribulbar anaesthesia (PBA) in patients undergoing routine cataract surgery on the basis of systemic adverse events., Methods: In this retrospective study, a total of 2,020 consecutive cases of cataract surgery performed by one surgeon on 1,621 patients with PBA (n = 1,010; between 1998-1999) or TA (n = 1,010; between 1999-2001) were evaluated on the basis of intra-operative and early postoperative adverse events requiring medical intervention., Results: The rate of pre-existing risk factors in patients undergoing cataract surgery is high (97%). Complications are significantly less frequent in TA than in PBA in the intra-operative (p < 0.001) and postoperative (p = 0.022) courses. The incidence of intra-operative complications is higher in elderly patients (>or=65 years of age) than in younger patients (p < 0.001)., Conclusion: The results from the present study indicate that intra-operative complications are less likely in patients that receive TA, suggesting the use of TA for routine cataract surgery both in young patients and particularly in elderly patients when there are no contraindications in the individual case., ((c) 2007 S. Karger AG, Basel.)
- Published
- 2007
- Full Text
- View/download PDF
25. Systemic application of pyrethroid insecticides evokes differential expression of c-Fos and c-Jun proteins in rat brain.
- Author
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Hassouna I, Wickert H, el-Elaimy I, Zimmermann M, and Herdegen T
- Subjects
- Animals, Behavior, Animal drug effects, Brain metabolism, Cerebral Cortex drug effects, Cerebral Cortex metabolism, Gene Expression drug effects, Hypothalamus drug effects, Hypothalamus metabolism, Male, Permethrin, Rats, Rats, Sprague-Dawley, Thalamus drug effects, Thalamus metabolism, Brain drug effects, Insecticides pharmacology, Proto-Oncogene Proteins c-fos metabolism, Proto-Oncogene Proteins c-jun metabolism, Pyrethrins pharmacology
- Abstract
Expression of the c-Fos and c-Jun transcription factor was investigated by immunocytochemistry in the thalamus, hypothalamus, hippocampus and cortex of adult rats following intraperitoneal application of proconvulsant doses of the pyrethroid insecticides, cypermethrin and permethrin. Pyrethroid insecticides are used world-wide and their uptake, e.g., by nutrition and inhalation evokes severe neurological symptoms in animals and humans, but their effects on neuronal gene expression has not been elucidated. Cypermethrin induced a strong expression of c-Fos and c-Jun in all the thalamic nuclei, except the ventro-posterior complex and substantia nigra, and in all the hypothalamic nuclei. In general, the immunoreactivities (IR) persisted for 8 h on their maximal levels, and were still above control levels after 24 h in several thalamic and hypothalamic areas. c-Fos-IR was strongly increased in all cortical layers with a predominance in the superficial layers II-IV, whereas c-Jun-IR was only slightly increased. In the hippocampus, cypermethrin induced a weak expression of c-Fos, but not of c-Jun, in the dentate gyrus and CA-3 area. Permethrin that has a lower pharmacological potency, evoked a similar pattern of c-Fos and c-Jun expression, however, intensity and persistence of the neuronal labeling were less pronounced. Our results demonstrate that the neurotoxic effects of pyrethroid insecticides comprise molecular genetic alterations in the brain such as early and lasting induction of Fos and Jun transcription factor proteins. These changes in the neuronal program are prominent in the hypothalamus and thalamus that are involved in the regulation of the autonomic and visceral nervous systems.
- Published
- 1996
26. [Information system for ambulant medical care in practice].
- Author
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Hassouna I
- Subjects
- Computers, Medical Records, Ambulatory Care, Information Services, Practice Management, Medical
- Published
- 1978
27. [The influence of ketamine on intra-ocular pressure (author's transl)].
- Author
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Purschke R and Hassouna I
- Subjects
- Adolescent, Audiometry, Blood Pressure drug effects, Child, Child, Preschool, Glaucoma surgery, Heart Rate drug effects, Humans, Tonometry, Ocular, Intraocular Pressure drug effects, Ketamine pharmacology
- Published
- 1973
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