Laquinimod ameliorates secondary brain inflammation
| Autor: | Joel Kaye, Julia Nedelcu, Zhan Jiangshan, Christoph Schmitz, Axel Rominger, Philipp Riedler, Christin Reinbach, Matthias Brendel, Markus Kipp, Newshan Behrangi |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty T cell Inflammation Neural degeneration 610 Medicine & health Quinolones Myelin oligodendrocyte glycoprotein lcsh:RC321-571 Multiple sclerosis 03 medical and health sciences chemistry.chemical_compound Cuprizone 0302 clinical medicine Immune system medicine Animals Gliosis lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Laquinimod biology business.industry Brain medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Neurology chemistry Forebrain biology.protein Encephalitis Female medicine.symptom Demyelination business 030217 neurology & neurosurgery |
| Zdroj: | Neurobiology of Disease, Vol 134, Iss, Pp-(2020) Nedelcu, Julia; Reinbach, Christin; Riedler, Philipp; Brendel, Matthias; Rominger, Axel; Kaye, Joel; Behrangi, Newshan; Jiangshan, Zhan; Schmitz, Christoph; Kipp, Markus (2020). Laquinimod ameliorates secondary brain inflammation. Neurobiology of disease, 134, p. 104675. Elsevier 10.1016/j.nbd.2019.104675 |
| DOI: | 10.7892/boris.136856 |
| Popis: | Accumulating evidence suggests that a degenerative processes within the brain can trigger the formation of new, focal inflammatory lesions in Multiple Sclerosis (MS). Here, we used a novel pre-clinical MS animal model to test whether the amelioration of degenerative brain events reduces the secondary recruitment of peripheral immune cells and, in consequence, inflammatory lesion development. Neural degeneration was induced by a 3 weeks cuprizone intoxication period. To mitigate the cuprizone-induced pathology, animals were treated with Laquinimod (25 mg/kg) during the cuprizone-intoxication period. At the beginning of week 6, encephalitogenic T cell development in peripheral lymphoid organs was induced by the immunization with myelin oligodendrocyte glycoprotein 35–55 peptide (i.e., Cup/EAE). Demyelination, axonal injury and reactive gliosis were determined by immunohistochemistry. Positron emission tomography (PET) imaging was performed to analyze glia activation in vivo. Vehicle-treated cuprizone mice displayed extensive callosal demyelination, glia activation and enhanced TSPO-ligand binding. This cuprizone-induced pathology was profoundly ameliorated in mice treated with Laquinimod. In vehicle-treated Cup/EAE mice, the cuprizone-induced pathology triggered massive peripheral immune cell recruitment into the forebrain, evidenced by multifocal perivascular inflammation, glia activation and neuro-axonal injury. While anti myelin oligodendrocyte glycoprotein 35–55 peptide immune responses were comparable in vehicle- and Laquinimod-treated Cup/EAE mice, the cuprizone-triggered immune cell recruitment was ameliorated by the Laquinimod treatment. This study clearly illustrates that amelioration of a primary brain-intrinsic degenerative process secondary halts peripheral immune cell recruitment and, in consequence, inflammatory lesion development. These findings have important consequences for the interpretation of the results of clinical studies. |
| Databáze: | OpenAIRE |
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