title: The Effect of Stereotactic Injections on Demyelination and Remyelination: a Study in the Cuprizone Model.
abstract: Remyelination is the natural repair mechanism in demyelinating disorders of the central nervous system (CNS) such as multiple sclerosis. Several animal models have been used to study demyelination and remyelination. Among toxic animal models, oral administration of the toxin cuprizone leads to white and gray matter demyelination. In contrast, focal demyelination models include the stereotactic application of a toxin such as lysolecithin or ethidium bromide. The injection procedure generates a local disruption of the blood-brain barrier (BBB) and might thus trigger a local inflammatory reaction and consequently may influence demyelination and remyelination. In order to study such consequences, we applied stereotactic injections in the cuprizone model where demyelination and remyelination are mediated independent of this procedure. Immunohistochemistry was performed to detect the presence of lymphocytes and activated glial cells in the injection area. Blood protein stainings were used to assess the integrity of the BBB and myelin staining to evaluate demyelination and remyelination processes. Stereotactic injection led to a local disruption of the BBB as shown by local extravasation of blood proteins. Along the injection canal, T and B lymphocytes could be detected and there was a tendency of a higher microgliosis and astrocytosis. However, these changes did not influence demyelination and remyelination processes at the site of injection, in the corpus callosum, or in the cerebral cortex. Our results suggest that a local stereotactic injection has no major impact on CNS demyelination and remyelination.
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str-1, 30625, Hannover, Germany.|Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Laura Salinas
authors.initials: LS
authors.lastname: Tejedor
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str-1, 30625, Hannover, Germany.|Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Wostradowski
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str-1, 30625, Hannover, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Gingele
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str-1, 30625, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Skripuletz
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str-1, 30625, Hannover, Germany. gudi.viktoria@mh-hannover.de.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Gudi
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str-1, 30625, Hannover, Germany.|Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Stangel
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D003337:Corpus Callosum / Q000187:drug effects / Q000473:pathology; D003471:Cuprizone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D005911:Gliosis / Q000209:etiology; D066128:Gray Matter / Q000187:drug effects / Q000473:pathology; D007276:Injections, Intraventricular; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D009186:Myelin Sheath / Q000187:drug effects* / Q000473:pathology; D013238:Stereotaxic Techniques
chemical_list: D008996:Monoamine Oxidase Inhibitors; D003471:Cuprizone
keywords: Corpus callosum; IgG; Immunohistochemistry; Intraventricular; cannula’s track