Dokument: Vergleich postischämischer Neuroinflammation zwischen zerebralem Kortex und Rückenmark
| Titel: | Vergleich postischämischer Neuroinflammation zwischen zerebralem Kortex und Rückenmark | |||||||
| Weiterer Titel: | Comparison of post-ischemic neuroinflammation between the cerebral cortex and the spinal cord | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=58306 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20211214-093415-0 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Deutsch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Jansen, Robin [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. med. Jander, Sebastian [Gutachter] PD Dr. Bönner, Florian [Gutachter] | |||||||
| Stichwörter: | neuroinflammation, stroke, spinal cord, spinal cord injury, photothrombosis, | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibungen: | Die Inzidenz der Schlaganfälle weltweit wird auf jährlich 15 Millionen geschätzt (WHO, 2012). In Deutschland ereignen sich jährlich ca. 262.000 Schlaganfälle, infolge derer etwa 63.000 Menschen versterben (Heuschmann et al., 2010). Während die akuttherapeutische Lysetherapie und die sekundärprophylaktische
Einstellung der kardiovaskulären Risikofaktoren sowie die Sekundärprophylaxe via medikamentöser Thrombozytenaggregationshemmung und oraler Antikoagulation feste Bestandteile einer leitliniengerechten Therapie bei Schlaganfall darstellen, ist die postischämische Immunantwort als Effektor von Reparatur und Schädigung zuletzt in den Fokus neurowissenschaftlicher Grundlagenforschung gerückt. Die im letzten Jahrzehnt erzielten technischen Fortschritte der Antikörpertherapie und die wachsenden Möglichkeiten der Genom-Editierung rücken gezielte Eingriffe in die inflammatorische Antwort in greifbare Nähe. Der Aufklärung der inflammatorischen Vorgänge nach Ischämie kommt somit eine essentielle Bedeutung zu. Kernstück dieser Arbeit stellt die von unserer Arbeitsgruppe etablierte Methode der Induktion vergleichbarer Läsionen in grauer- (Cortex) und weißer Substanz (Rückenmark) via Photothrombose dar. Ein auf dem gleichen Pathomechanismus beruhender Vergleich der postischämischen Immunantwort in grauer und weißer Substanz ist mit den verwendeten Methoden zum jetzigen Zeitpunkt erstmals möglich und kann Hinweise geben, ob die therapeutische Manipulation an differenziell ausgeprägte inflammatorische Antworten in unterschiedlichen ZNS Kompartimenten angepasst werden muss. Zum ersten Mal konnte in einem Vergleichsmodell gezeigt werden, dass die postischämische Immunantwort spinal zu einem größeren Anteil als zerebral auf hämatogen eingewanderten Monozyten/Makrophagen beruht und zerebral zu einem höheren Anteil auf einer mikroglialen Immunantwort. Gleichzeitig ist die resultierende inflammatorische Antwort auf Transkriptomebene nach der Ischämie in beiden Geweben sehr ähnlich sowohl im Hinblick auf Inflammation als auch in Hinblick auf Reparatur. Einen interessanten Unterschied deckte die Transkriptomanalyse auf. Anhand von etablierten Gendatenbanken konnte der Nachweis einer verstärkten Expression remyelinisierungsspezifischer Gene nach zerebraler Ischämie nachgewiesen werden.Based on data supplied by the WHO the number of strokes worldwide is estimated by 15 million a year. Numbers from Germany estimate around 262.000 strokes with around 63.000 deaths a year (Heuschmann et al., 2010). While thrombolysis, control of cardiovascular risk factors and secondary prophylaxis via drug for inhibition of platelet aggregation or anticoagulation are fixed components of guideline-based therapy for stroke, the post-ischemic immune response as an effector of repair and damage has recently gained attention of neuroscientific research. In the past ten years technical advances made in antibody therapy and genome editing are bringing targeted therapy concepts within reach. The exact decryption of postischemic inflammatory processes is a critical part for the identification of new drug targets. The core work of this dissertation is the method of inducing comparable lesions in gray (cortex) and white matter (spinal cord) via photothrombosis. We provide the first comparison of postischemic immune response in white- and gray matter based on the same pathomechanism. For the first time, a valid comparative model was able to show that the spinal postischemic immune response is based to a greater extent on hematogenously immigrated monocytes / macrophages and granulocytes than the cerebral postischemic immune response. Vice versa the cerebral immune response is dominated by microglial cells. At the same time, the resulting inflammatory response after ischemia is comparable in both tissues at the transcriptome level, both in terms of inflammation and in terms of repair. However, the transcriptome analysis revealed an interesting difference. With the help of established gene databases, evidence of increased expression of myelination-specific genes after cerebral ischemia could be demonstrated. | |||||||
| Quelle: | Abdul-Majid, K. B., et al. (2002). "Fc receptors are critical for autoimmune
inflammatory damage to the central nervous system in experimental autoimmune encephalomyelitis." Scandinavian journal of immunology 55(1): 70-81. Ajami, B., et al. (2011). "Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool." Nat Neurosci 14(9): 1142-1149. Amiri-Nikpour, M. R., et al. (2015). "An open-label evaluator-blinded clinical study of minocycline neuroprotection in ischemic stroke: gender-dependent effect." Acta Neurol Scand 131(1): 45-50. Anania, J. C., et al. (2019). "The human FcγRII (CD32) family of leukocyte FcR in health and disease." Front Immunol 10: 464. Aquino, D. A., et al. (1988). "Glial fibrillary acidic protein increases in the spinal cord of Lewis rats with acute experimental autoimmune encephalomyelitis." J Neurochem 51(4): 1085-1096. Arnett, H. A., et al. (2001). "TNFα promotes proliferation of oligodendrocyte progenitors and remyelination." Nat Neurosci 4(11): 1116-1122. Arnold, L., et al. (2007). "Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis." J Exp Med 204(5): 1057-1069. Bangham, A. D. and R. W. Horne (1964). "Negative staining of phospholipids and their modification by surface-active agents as observed in the electron microscope." J Mol Biol 8: 660-668. Banisadr, G., et al. (2002). "Distribution, cellular localization and functional role of CCR2 chemokine receptors in adult rat brain." J Neurochem 81. Batchelor, P. E., et al. (2008). "Comparison of inflammation in the brain and spinal cord following mechanical injury." J Neurotrauma 25(10): 1217-1225. Bauer, J., et al. (1995). "The role of macrophages, perivascular cells, and microglial cells in the pathogenesis of experimental autoimmune encephalomyelitis." Glia 15(4): 437-446. Baumgarth, N. and M. Roederer (2000). "A practical approach to multicolor flow cytometry for immunophenotyping." J Immunol Methods 243. Beech, J. S., et al. (2001). "Neuroprotection in ischemia–reperfusion injury: an antiinflammatory approach using a novel broad-spectrum chemokine inhibitor." Journal of Cerebral Blood Flow & Metabolism 21(6): 683-689. Literatur und Quellenverzeichnis 73 Bellver-Landete, V., et al. (2019). "Microglia are an essential component of the neuroprotective scar that forms after spinal cord injury." Nat Commun 10(1): 518. Bennett, M. L., et al. (2016). "New tools for studying microglia in the mouse and human CNS." Proc Natl Acad Sci 113. Berkhemer, O. A., et al. (2015). "A randomized trial of intraarterial treatment for acute ischemic stroke." N Engl J Med 372: 11-20. Berkhemer, O. A., et al. (2015). "A randomized trial of intraarterial treatment for acute ischemic stroke." N Engl J Med 372: 11-20. Biburger, M., et al. (2011). "Monocyte subsets responsible for immunoglobulin Gdependent effector functions in vivo." Immunity 35(6): 932-944. Boddeke, E. W. G. M., et al. (1999). "Cultured rat microglia express functional βchemokine receptors." J Neuroimmunol 98. Bolstad, B. M., et al. (2003). "A comparison of normalization methods for high density oligonucleotide array data based on variance and bias." Bioinformatics 19(2): 185-193. Bowman, R. L., et al. (2016). "Macrophage ontogeny underlies differences in tumor-specific education in brain malignancies." Cell Rep 17. Brahmachari, S., et al. (2006). "Induction of Glial Fibrillary Acidic Protein Expression in Astrocytes by Nitric Oxide." The Journal of Neuroscience 26(18): 4930-4939. Brandenburg, S., et al. (2016). "Resident microglia rather than peripheral macrophages promote vascularization in brain tumors and are source of alternative pro-angiogenic factors." Acta Neuropathol 131. Butovsky, O., et al. (2014). "Identification of a unique TGF-beta-dependent molecular and functional signature in microglia." Nat Neurosci 17(1): 131-143. Cardona, A. E., et al. (2006). "Isolation of murine microglial cells for RNA analysis or flow cytometry." Nat Protoc 1. Cardona, A. E., et al. (2006). "Control of microglial neurotoxicity by the fractalkine receptor." Nat Neurosci 9(7): 917-924. Campbell, B. C., et al. (2015). "Endovascular therapy for ischemic stroke with perfusion-imaging selection." New England Journal of Medicine 372(11): 1009- 1018. Chang, A., et al. (2012). "Cortical remyelination: a new target for repair therapies in multiple sclerosis." Ann Neurol 72(6): 918-926. Chao, C. C., et al. (1995). "Interleukin-1 and tumor necrosis factor-alpha synergistically mediate neurotoxicity: involvement of nitric oxide and of N-methylD-aspartate receptors." Brain Behav Immun 9(4): 355-365. Literatur und Quellenverzeichnis 74 Chen, Y., et al. (2014). "Targeting microglial activation in stroke therapy: pharmacological tools and gender effects." Current medicinal chemistry 21(19): 2146-2155. Chen, Z., et al. (2017). "Cellular and molecular identity of tumor-associated macrophages in glioblastoma." Cancer Res 77. Chirgwin, J. M., et al. (1979). "Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease." Biochemistry 18(24): 5294-5299. Chistiakov, D. A., et al. (2017). "CD68/macrosialin: not just a histochemical marker." Lab Invest 97(1): 4-13. Chiu, I. M., et al. (2013). "A neurodegeneration-specific gene-expression signature of acutely isolated microglia from an amyotrophic lateral sclerosis mouse model." Cell Rep 4. Chu, H. X., et al. (2015). "Evidence that Ly6Chi monocytes are protective in acute ischemic stroke by promoting M2 macrophage polarization." Stroke 46(7): 1929- 1937. Courties, G., et al. (2015). "Ischemic stroke activates hematopoietic bone marrow stem cells." Circ Res 116(3): 407-417. Cox, J. and M. Mann (2008). "MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification." Nat Biotechnol 26. Davalos, D., et al. (2005). "ATP mediates rapid microglial response to local brain injury in vivo." Nat Neurosci 8(6): 752-758. David, S. and A. Kroner (2011). "Repertoire of microglial and macrophage responses after spinal cord injury." Nature Reviews Neuroscience 12(7): 388. David, S., et al. (2018). "Myeloid cell responses after spinal cord injury." J Neuroimmunol 321: 97-108. Davies, C. L., et al. (2019). "Myeloid cell and transcriptome signatures associated with inflammation resolution in a model of self-limiting acute brain inflammation." Front Immunol 10: 1048. De Godoy, I., et al. (1996). "Elevated TNF-alpha production by peripheral blood monocytes of weight-losing COPD patients." American Journal of Respiratory and Critical Care Medicine 153(2): 633-637. Deshmane, S. L., et al. (2009). "Monocyte chemoattractant protein-1 (MCP-1): an overview." J Interferon Cytokine Res 29(6): 313-326. Dewar, D., et al. (2003). "Oligodendrocytes and ischemic brain injury." Journal of Cerebral Blood Flow & Metabolism 23(3): 263-274. Literatur und Quellenverzeichnis 75 Dimitrijevic, O. B., et al. (2007). "Absence of the chemokine receptor CCR2 protects against cerebral ischemia/reperfusion injury in mice." Stroke 38(4): 1345-1353. Donnelly, D. J. and P. G. Popovich (2008). "Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury." Exp Neurol 209(2): 378-388. Duffield, J. S., et al. (2005). "Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair." J Clin Invest 115(1): 56-65. Dugue, R., et al. (2017). "Roles of pro-and anti-inflammatory cytokines in traumatic brain injury and acute ischemic stroke." Mechanisms of neuroinflammation. London: IntechOpen: 211-261. Eng, L. F. (1985). "Glial fibrillary acidic protein (GFAP): the major protein of glial intermediate filaments in differentiated astrocytes." Journal of Neuroimmunology 8: 203-214. Fedorcsák, I. E., L. (1966). "Effects of Diethyl Polycarbonate and Methyl Methanesulfonate on Nucleic Acids and Nucleases " Acta Chemica Scandinavica 20: 107-112. Fernández-Castañeda, A., et al. (2020). "The active contribution of OPCs to neuroinflammation is mediated by LRP1." Acta neuropathologica 139(2): 365- 382. Ford, A. L., et al. (1995). "Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting: phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4+ T cells compared." J Immunol 154. Galloway, D. A., et al. (2019). "Phagocytosis in the Brain: Homeostasis and Disease." Front Immunol 10: 790. Gandin, E., et al. (1983). "QUANTUM YIELD OF SINGLET OXYGEN PRODUCTION BY XANTHENE DERIVATIVES." Photochemistry and Photobiology 37(3): 271-278. Gautier, E. L., et al. (2012). "Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages." Nat Immunol 13. Geissmann, F., et al. (2003). "Blood monocytes consist of two principal subsets with distinct migratory properties." Immunity 19(1): 71-82. Geissmann, F., et al. (2010). "Development of monocytes, macrophages, and dendritic cells." Science 327(5966): 656-661. Literatur und Quellenverzeichnis 76 Gelderblom, M., et al. (2009). "Temporal and spatial dynamics of cerebral immune cell accumulation in stroke." Stroke 40(5): 1849-1857. Ginhoux, F., et al. (2010). "Fate mapping analysis reveals that adult microglia derive from primitive macrophages." Science 330(6005): 841-845. Giulian, D., et al. (1988). "Interleukin-1 injected into mammalian brain stimulates astrogliosis and neovascularization." The Journal of Neuroscience 8(7): 2485- 2490. Giulian, D. and C. Robertson (1990). "Inhibition of mononuclear phagocytes reduces ischemic injury in the spinal cord." Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society 27(1): 33-42. Gliem, M., et al. (2012). "Macrophages prevent hemorrhagic infarct transformation in murine stroke models." Ann Neurol 71(6): 743-752. Gliem, M., et al. (2015). "Hyperglycemia and PPARgamma Antagonistically Influence Macrophage Polarization and Infarct Healing After Ischemic Stroke." Stroke 46(10): 2935-2942. Gliem, M., et al. (2015). "Macrophage-derived osteopontin induces reactive astrocyte polarization and promotes re-establishment of the blood brain barrier after ischemic stroke." Glia 63(12): 2198-2207. Gliem, M., et al. (2016). "Protective features of peripheral monocytes/macrophages in stroke." Biochim Biophys Acta 1862(3): 329-338. Gomez Perdiguero, E., et al. (2013). "Development and homeostasis of “resident” myeloid cells: the case of the microglia." Glia 61. Govindan, R., et al. (2012). "Genomic landscape of non-small cell lung cancer in smokers and never-smokers." Cell 150. Greenhalgh, A. D., et al. (2016). "Arginase-1 is expressed exclusively by infiltrating myeloid cells in CNS injury and disease." Brain Behav Immun 56: 61- 67. Gregoriadis, G. (1988). "Liposomes as a drug delivery system: optimization studies." Adv Exp Med Biol 238: 151-159. Grishagin, I. V. (2015). "Automatic cell counting with ImageJ." Anal Biochem 473: 63-65. Grotendorst, G. R., et al. (1989). "Production of transforming growth factor beta by human peripheral blood monocytes and neutrophils." Journal of cellular physiology 140(2): 396-402. Literatur und Quellenverzeichnis 77 Guesdon, J. L., et al. (1979). "The use of avidin-biotin interaction in immunoenzymatic techniques." Journal of Histochemistry & Cytochemistry 27(8): 1131-1139. Haage, V., et al. (2019). "Comprehensive gene expression meta-analysis identifies signature genes that distinguish microglia from peripheral monocytes/macrophages in health and glioma." Acta Neuropathologica Communications 7(1): 20. Hacke, W., et al. (2008). "Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke." New England Journal of Medicine 359(13): 1317-1329. Hambardzumyan, D., et al. (2009). "Modeling adult gliomas using RCAS/t-va technology." Transl Oncol 2. Heiss, W. D. (1992). "Experimental evidence of ischemic thresholds and functional recovery." Stroke 23(11): 1668-1672. Henrich-Noack, P., et al. (1996). "TGF-beta 1 protects hippocampal neurons against degeneration caused by transient global ischemia. Dose-response relationship and potential neuroprotective mechanisms." Stroke 27(9): 1609- 1614; discussion 1615. Herrmann, K. S. (1983). "Platelet aggregation induced in the hamster cheek pouch by a photochemical process with excited fluorescein isothiocyanatedextran." Microvasc Res 26(2): 238-249. Heuschmann, P. U., et al. (2010). "Schlaganfallhäufigkeit und versorgung von schlaganfallpatienten in deutschland." Aktuelle Neurologie 37(07): 333-340. Hewett, S. J., et al. (1994). "Selective potentiation of NMDA-induced neuronal injury following induction of astrocytic iNOS." Neuron 13(2): 487-494. Hickman, S. E., et al. (2013). "The microglial sensome revealed by direct RNA sequencing." Nat Neurosci 16. Hilgendorf, I., et al. (2014). "Ly-6Chigh monocytes depend on Nr4a1 to balance both inflammatory and reparative phases in the infarcted myocardium." Circ Res 114(10): 1611-1622. Hirbec, H., et al. (2018). "The microglial reaction signature revealed by RNAseq from individual mice." Glia 66. Holness, C. and D. Simmons (1993). "Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins." Blood 81(6): 1607- 1613. Holness CL, da Silva RP, Fawcett J, Gordon S, Simmons DL. (1993 ). Macrosialin, a mouse macrophage-restricted glycoprotein, is a member of the lamp/lgp family. J Biol Chem. . Literatur und Quellenverzeichnis 78 Hristovska, I. and O. Pascual (2015). "Deciphering Resting Microglial Morphology and Process Motility from a Synaptic Prospect." Front Integr Neurosci 9: 73. Hu, X., et al. (2012). "Microglia/macrophage polarization dynamics reveal novel mechanism of injury expansion after focal cerebral ischemia." Stroke 43(11): 3063-3070 Hughes, P. M., et al. (2002). "Monocyte chemoattractant protein-1 deficiency is protective in a murine stroke model." J Cereb Blood Flow Metab 22(3): 308-317. Iadecola, C. and J. Anrather (2011). "The immunology of stroke: from mechanisms to translation." Nat Med 17(7): 796-808. Imai, T., et al. (1997). "Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion." Cell 91. Ito, M., et al. (2019). "Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery." Nature 565(7738): 246-250. Jayaraj, R. L., et al. (2019). "Neuroinflammation: friend and foe for ischemic stroke." J Neuroinflammation 16(1): 142. Jeong, H.-K., et al. (2013). "Brain inflammation and microglia: facts and misconceptions." Exp Neurobiol 22(2): 59-67. Jeong, H. K., et al. (2013). "Brain inflammation and microglia: facts and misconceptions." Exp Neurobiol 22(2): 59-67. Jin, R., et al. (2010). "Inflammatory mechanisms in ischemic stroke: role of inflammatory cells." J Leukoc Biol 87(5): 779-789. Jordão, M. J. C., et al. (2019). "Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation." Science 363(6425): eaat7554. Jung, S., et al. (2000). "Analysis of Fractalkine receptor CX3CR1 function by targeted deletion and green fluorescent protein reporter gene insertion." Mol Cell Biol 20. Kakuda, D. K., et al. (1999). "CAT2-mediated L-arginine transport and nitric oxide production in activated macrophages." Biochem J 340 ( Pt 2): 549-553. Kanashova, T., et al. (2015). "Differential proteomic analysis of mouse macrophages exposed to adsorbate-loaded heavy fuel oil derived combustion particles using an automated sample-preparation workflow aerosols and health." Anal Bioanal Chem 407. Káradóttir, R., et al. (2005). "NMDA receptors are expressed in oligodendrocytes and activated in ischaemia." Nature 438(7071): 1162-1166. Literatur und Quellenverzeichnis 79 Keren-Shaul, H., et al. (2017). "A unique microglia type associated with restricting development of Alzheimer’s disease." Cell 169. Khare, P., et al. (2018). "Myelin oligodendrocyte glycoprotein-specific antibodies from multiple sclerosis patients exacerbate disease in a humanized mouse model." Journal of Autoimmunity 86: 104-115. Kigerl, K. A., et al. (2009). "Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord." J Neurosci 29(43): 13435-13444. Kim, J. Y., et al. (2016). "Inflammation after Ischemic Stroke: The Role of Leukocytes and Glial Cells." Exp Neurobiol 25(5): 241-251. Kohler, E., et al. (2013). "Intravenous minocycline in acute stroke: a randomized, controlled pilot study and meta-analysis." Stroke 44(9): 2493-2499. Kolominsky-Rabas, P. L., et al. (2006). "Lifetime cost of ischemic stroke in Germany: results and national projections from a population-based stroke registry: the Erlangen Stroke Project." Stroke 37(5): 1179-1183. Konishi, H., et al. (2017). "Siglec-H is a microglia-specific marker that discriminates microglia from CNS-associated macrophages and CNS-infiltrating monocytes." Glia 65. Lalancette-Hebert, M., et al. (2012). "Galectin-3 is required for resident microglia activation and proliferation in response to ischemic injury." J Neurosci 32(30): 10383-10395. Lambertsen, K. L., et al. (2019). "Post-stroke inflammation-target or tool for therapy?" Acta Neuropathol 137(5): 693-714. Lampl, Y., et al. (2007). "Minocycline treatment in acute stroke: an open-label, evaluator-blinded study." Neurology 69(14): 1404-1410. Landsman, L., et al. (2009). "CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival." Blood 113(4): 963-972. Lee, P. Y., et al. (2013). "Ly6 family proteins in neutrophil biology." J Leukoc Biol 94(4): 585-594. Lee, Y., et al. (2014). "Therapeutically targeting neuroinflammation and microglia after acute ischemic stroke." Biomed Res Int 2014: 297241. Li, J., et al. (2008). "Tumor necrosis factor α mediates lipopolysaccharideinduced microglial toxicity to developing oligodendrocytes when astrocytes are present." Journal of Neuroscience 28(20): 5321-5330. Li, J., et al. (2016). "Astrocytes in oligodendrocyte lineage development and white matter pathology." Frontiers in cellular neuroscience 10: 119. Literatur und Quellenverzeichnis 80 Liang, D., et al. (2007). "Cytotoxic edema: mechanisms of pathological cell swelling." Neurosurg Focus 22(5): E2. Licinio, J., et al. (1999). "Brain iNOS: current understanding and clinical implications." Mol Med Today 5(5): 225-232. Liedtke, W., et al. (1996). "GFAP Is Necessary for the Integrity of CNS White Matter Architecture and Long-Term Maintenance of Myelination." Neuron 17(4): 607-615. Lim, S. W., et al. (2013). "Microglial activation induced by traumatic brain injury is suppressed by postinjury treatment with hyperbaric oxygen therapy." J Surg Res 184(2): 1076-1084. Liska, G. M., et al. (2018). "A Dual Role for Hyperbaric Oxygen in Stroke Neuroprotection: Preconditioning of the Brain and Stem Cells." Cond Med 1(4): 151-166. Liu, T., et al. (1994). "Tumor necrosis factor-alpha expression in ischemic neurons." Stroke 25(7): 1481-1488. Lu, H., et al. (2011). "Macrophages recruited via CCR2 produce insulin-like growth factor-1 to repair acute skeletal muscle injury." Faseb j 25(1): 358-369. Lucas, T., et al. (2010). "Differential roles of macrophages in diverse phases of skin repair." J Immunol 184(7): 3964-3977. Ma, M. W., et al. (2017). "NADPH oxidase in brain injury and neurodegenerative disorders." Molecular neurodegeneration 12(1): 7. Malone, K., et al. (2019). "Immunomodulatory therapeutic strategies in stroke." Frontiers in pharmacology 10: 630. Mardis, E. R., et al. (2009). "Recurring mutations found by sequencing an acute myeloid leukemia genome." N Engl J Med 361. Marques, C. P., et al. (2008). "Microglia are the major cellular source of inducible nitric oxide synthase during experimental herpes encephalitis." J Neurovirol 14(3): 229-238. Marsh, B. J., et al. (2009). "Toll-like receptor signaling in endogenous neuroprotection and stroke." Neuroscience 158(3): 1007-1020. Matsumoto, S., et al. (2003). "The temporal profile of the reaction of microglia, astrocytes, and macrophages in the delayed onset paraplegia after transient spinal cord ischemia in rabbits." Anesth Analg 96(6): 1777-1784, table of contents. Mawhinney, L. A., et al. (2012). "Differential detection and distribution of microglial and hematogenous macrophage populations in the injured spinal cord Literatur und Quellenverzeichnis 81 of lys-EGFP-ki transgenic mice." Journal of Neuropathology & Experimental Neurology 71(3): 180-197. McKinnon, R. D., et al. (1993). "A role for TGF-beta in oligodendrocyte differentiation." The Journal of cell biology 121(6): 1397-1407. McTigue, D. M., et al. (2000). "Localization of transforming growth factor-β1 and receptor mRNA after experimental spinal cord injury." Exp Neurol 163(1): 220- 230. Melani, A., et al. (2005). "ATP extracellular concentrations are increased in the rat striatum during in vivo ischemia." Neurochem Int 47(6): 442-448. Meller, R., et al. (2005). "Neuroprotection by Osteopontin in Stroke." Journal of Cerebral Blood Flow & Metabolism 25(2): 217-225. Merrill, J., et al. (1993). "Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide." The Journal of Immunology 151(4): 2132-2141. Merrill, J. E., et al. (1997). "Inducible nitric oxide synthase and nitric oxide production by oligodendrocytes." Journal of neuroscience research 48(4): 372- 384. Michinaga, S. and Y. Koyama (2015). "Pathogenesis of brain edema and investigation into anti-edema drugs." International journal of molecular sciences 16(5): 9949-9975. Middeldorp, J. and E. M. Hol (2011). "GFAP in health and disease." Prog Neurobiol 93(3): 421-443. Mildner, A., et al. (2007). "Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions." Nat Neurosci 10(12): 1544-1553. Mirabelli-Badenier, M., et al. (2011). "CC and CXC chemokines are pivotal mediators of cerebral injury in ischaemic stroke." Thrombosis and haemostasis 105(03): 409-420. Moore, C. S., et al. (2015). "P2Y12 expression and function in alternatively activated human microglia." Neurol Neuroimmunol Neuroinflamm 2(2): e80. Müller, A., et al. (2015). "Resident microglia, and not peripheral macrophages, are the main source of brain tumor mononuclear cells." Int J Cancer 137. Mullis, K. B. and F. A. Faloona (1987). "Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction." Methods Enzymol 155: 335-350. Nahrendorf, M., et al. (2007). "The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions." J Exp Med 204(12): 3037-3047. Nicholson, B., et al. (2001). "Sustained nitric oxide production in macrophages requires the arginine transporter CAT2." J Biol Chem 276(19): 15881-15885. Literatur und Quellenverzeichnis 82 Nissl, F. (1894). "Ueber eine neue Untersuchungsmethode des Centralorgans zur Feststellung der Localisation der Nervenzellen." Neurologisches Centralblatt 13: 507-508. Novy, J., et al. (2006). "Spinal cord ischemia: clinical and imaging patterns, pathogenesis, and outcomes in 27 patients." Archives of neurology 63(8): 1113- 1120. Odegaard, J. I., et al. (2007). "Macrophage-specific PPARγ controls alternative activation and improves insulin resistance." Nature 447(7148): 1116. Ogawa, K., et al. (1989). "Distribution of collagen type IV in brain tumors: an immunohistochemical study." J Neurooncol 7(4): 357-366. Olah, M., et al. (2012). "Identification of a microglia phenotype supportive of remyelination." Glia 60(2): 306-321. Pang, Y., et al. (2003). "Disturbance of oligodendrocyte development, hypomyelination and white matter injury in the neonatal rat brain after intracerebral injection of lipopolysaccharide." Developmental Brain Research 140(2): 205-214. Peferoen, L., et al. (2014). "Oligodendrocyte-microglia cross-talk in the central nervous system." Immunology 141(3): 302-313. Pekny, M. and M. Pekna (2004). "Astrocyte intermediate filaments in CNS pathologies and regeneration." The Journal of Pathology 204(4): 428-437. Pineau, I. and S. Lacroix (2007). "Proinflammatory cytokine synthesis in the injured mouse spinal cord: multiphasic expression pattern and identification of the cell types involved." Journal of Comparative Neurology 500(2): 267-285. Piotr Chomczynski, N. S. (1987). "Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction." Analytical Biochemistry 162(1): 156-159. Pocock, J. M. and H. Kettenmann (2007). "Neurotransmitter receptors on microglia." Trends Neurosci 30(10): 527-535. Polfliet, M. M., et al. (2001). "A method for the selective depletion of perivascular and meningeal macrophages in the central nervous system." J Neuroimmunol 116(2): 188-195. Pong, W. W., et al. (2013). "F11R is a novel monocyte prognostic biomarker for malignant glioma." PLoS One 8. Popovich, P. G., et al. (1999). "Depletion of hematogenous macrophages promotes partial hindlimb recovery and neuroanatomical repair after experimental spinal cord injury." Exp Neurol 158(2): 351-365. Literatur und Quellenverzeichnis 83 Prehn, J. H., et al. (1993). "Transforming growth factor-β1 prevents glutamate neurotoxicity in rat neocortical cultures and protects mouse neocortex from ischemic injury in vivo." Journal of Cerebral Blood Flow & Metabolism 13(3): 521- 525. Prinz, M., et al. (2017). "Ontogeny and homeostasis of CNS myeloid cells." Nat Immunol 18. Qureshi, A. I., et al. (2017). "A Population-Based Study of the Incidence of Acute Spinal Cord Infarction." J Vasc Interv Neurol 9(4): 44-48. Rahman, M., et al. (2014). "The β-hydroxybutyrate receptor HCA 2 activates a neuroprotective subset of macrophages." Nat Commun 5(1): 1-11. Ransohoff, R. M. and A. E. Cardona (2010). "The myeloid cells of the central nervous system parenchyma." Nature 468(7321): 253-262. Rappsilber, J., et al. (2007). "Protocol for micro-purification, enrichment, prefractionation and storage of peptides for proteomics using StageTips." Nat Protoc 2. Renno, T., et al. (1995). "TNF-alpha expression by resident microglia and infiltrating leukocytes in the central nervous system of mice with experimental allergic encephalomyelitis. Regulation by Th1 cytokines." J Immunol 154(2): 944- 953. Ringnér, M. (2008). "What is principal component analysis?" Nature biotechnology 26(3): 303-304. Roberts, A., et al. (2011). "Identification of novel transcripts in annotated genomes using RNA-seq." Bioinformatics 27. Rubin, P., et al. (1994). "Disruption of the blood-brain barrier as the primary effect of CNS irradiation." Radiother Oncol 31(1): 51-60. Sacco, R. L., et al. (2013). "An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association." Stroke 44(7): 2064-2089. Sandson, T. A. and J. H. Friedman (1989). "Spinal cord infarction. Report of 8 cases and review of the literature." Medicine (Baltimore) 68(5): 282-292. Saver, J. L., et al. (2015). "Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke." New England Journal of Medicine 372(24): 2285-2295. Schmidt-Pogoda, A., et al. (2019). "Immunology of stroke: from animal models to clinical trials." Ther Adv Neurol Disord 12: 1756286419830862. Literatur und Quellenverzeichnis 84 Schnell, L., et al. (1999). "Acute inflammatory responses to mechanical lesions in the CNS: differences between brain and spinal cord." Eur J Neurosci 11(10): 3648-3658. Sedgwick, J. D., et al. (1991). "Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system." Proc Natl Acad Sci U S A 88(16): 7438-7442. Seidenwurm, D. (2008). "Myelopathy." American Journal of Neuroradiology 29(5): 1032-1034. Sela, M., et al. (1957). "The correlation of ribonuclease activity with specific aspects of tertiary structure." Biochim Biophys Acta 26(3): 502-512. Serbina, N. V. and E. G. Pamer (2006). "Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2." Nat Immunol 7(3): 311-317. Shechter, R., et al. (2013). "Recruitment of beneficial M2 macrophages to injured spinal cord is orchestrated by remote brain choroid plexus." Immunity 38(3): 555- 569. Shevchenko, A., et al. (2007). "In-gel digestion for mass spectrometric characterization of proteins and proteomes." Nat Protoc 1. Singh, K., et al. (2016). "The L-Arginine Transporter Solute Carrier Family 7 Member 2 Mediates the Immunopathogenesis of Attaching and Effacing Bacteria." PLoS Pathog 12(10): e1005984. Smith, P. D., et al. (2013). "Preservation of motor function after spinal cord ischemia and reperfusion injury through microglial inhibition." Ann Thorac Surg 95(5): 1647-1653. Smyth, G. K. (2004). "Linear models and empirical bayes methods for assessing differential expression in microarray experiments." Stat Appl Genet Mol Biol 3: Article3. Solga, A. C., et al. (2015). "RNA sequencing of tumor-associated microglia reveals Ccl5 as a stromal chemokine critical for Neurofibromatosis-1 glioma growth." Neoplasia 17. Spangenberg, E. E., et al. (2016). "Eliminating microglia in Alzheimer's mice prevents neuronal loss without modulating amyloid-beta pathology." Brain 139(Pt 4): 1265-1281. Stirling, D. P. and V. W. Yong (2008). "Dynamics of the inflammatory response after murine spinal cord injury revealed by flow cytometry." Journal of neuroscience research 86(9): 1944-1958. Srivastava, M. P., et al. (2012). "Efficacy of minocycline in acute ischemic stroke: a single-blinded, placebo-controlled trial." Neurology India 60(1): 23. Literatur und Quellenverzeichnis 85 Su, D. and N. Van Rooijen (1989). "The role of macrophages in the immunoadjuvant action of liposomes: effects of elimination of splenic macrophages on the immune response against intravenously injected liposomeassociated albumin antigen." Immunology 66(3): 466-470. Sun, M., et al. (2015). "Isoflurane preconditioning provides neuroprotection against stroke by regulating the expression of the TLR4 signalling pathway to alleviate microglial activation." Scientific Reports 5: 11445. Tataurov, A. V., et al. (2008). "Predicting ultraviolet spectrum of single stranded and double stranded deoxyribonucleic acids." Biophys Chem 133(1-3): 66-70. Tator, C. H. and I. Koyanagi (1997). "Vascular mechanisms in the pathophysiology of human spinal cord injury." Journal of neurosurgery 86(3): 483- 492. Taylor, R. A., et al. (2017). "TGF-beta1 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage." J Clin Invest 127(1): 280- 292. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group,1995 "Tissue plasminogen activator for acute ischemic stroke." New England Journal of Medicine 333(24): 1581-1588. Tobinick, E., et al. (2014). "Immediate neurological recovery following perispinal etanercept years after brain injury." Clinical drug investigation 34(5): 361-366. Trapnell, C., et al. (2009). "TopHat: discovering splice junctions with RNA-Seq." Bioinformatics 25. Trapnell, C., et al. (2013). "Differential analysis of gene regulation at transcript resolution with RNA-seq." Nat Biotechnol 31. Tunstall-Pedoe, H. (1988). "The World Health Organization MONICA Project (monitoring trends and determinants in cardiovascular disease): a major international collaboration. WHO MONICA Project Principal Investigators." J Clin Epidemiol 41(2): 105-114. van Amerongen, M. J., et al. (2007). "Macrophage depletion impairs wound healing and increases left ventricular remodeling after myocardial injury in mice." Am J Pathol 170(3): 818-829. Van Rooijen, N. (1989). "The liposome-mediated macrophage 'suicide' technique." J Immunol Methods 124(1): 1-6.. Van Rooijen, N. and A. Sanders (1994). "Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications." J Immunol Methods 174(1-2): 83-93. Literatur und Quellenverzeichnis 86 van Rooijen, N. and R. van Nieuwmegen (1980). "Liposomes in immunology: evidence that their adjuvant effect results from surface exposition of the antigens." Cell Immunol 49(2): 402-407. Veltkamp, R. and D. Gill (2016). "Clinical Trials of Immunomodulation in Ischemic Stroke." Neurotherapeutics 13(4): 791-800. Vuong, S. M., et al. (2016). "Vascular Diseases of the Spinal Cord: Infarction, Hemorrhage, and Venous Congestive Myelopathy." Semin Ultrasound CT MR 37(5): 466-481. Watson, B. D., et al. (1985). "Induction of reproducible brain infarction by photochemically initiated thrombosis." Ann Neurol 17(5): 497-504. Weidauer, S., et al. (2002). "Spinal cord infarction: MR imaging and clinical features in 16 cases." Neuroradiology 44(10): 851-857. Wiessner, C., et al. (1993). "Expression of transforming growth factor-β1 and interleukin-1β mRNA in rat brain following transient forebrain ischemia." Acta neuropathologica 86(5): 439-446. Wolf, S. A., et al. (2017). "Microglia in physiology and disease." Annu Rev Physiol 79. Xie, Q. W., et al. (1992). "Cloning and characterization of inducible nitric oxide synthase from mouse macrophages." Science 256(5054): 225-228. Xiong, X. Y., et al. (2016). "Functions and mechanisms of microglia/macrophages in neuroinflammation and neurogenesis after stroke." Prog Neurobiol 142: 23-44. Xue, J., et al. (2014). "Transcriptome-based network analysis reveals a spectrum model of human macrophage activation." Immunity 40(2): 274-288. Yahn, S. L., et al. (2020). "Fibrotic scar after experimental autoimmune encephalomyelitis inhibits oligodendrocyte differentiation." Neurobiology of Disease 134: 104674. Yona, S., et al. (2013). "Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis." Immunity 38. Zhang, D., et al. (2010). "Astrogliosis in CNS Pathologies: Is There A Role for Microglia?" Molecular Neurobiology 41(2 %@ 1559-1182): 232-241. Zhang, J., et al. (2007). "Expression of CCR2 in both resident and bone marrowderived microglia plays a critical role in neuropathic pain." J Neurosci 27. Zhang, Y., et al. (2014). "An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex." J Neurosci 34. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Bezug: | 2016-2021 | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 14.12.2021 | |||||||
| Dateien geändert am: | 14.12.2021 | |||||||
| Promotionsantrag am: | 08.04.2021 | |||||||
| Datum der Promotion: | 09.12.2021 |
