Influencia del sistema inmune innato sobre la neuroinflamación crónica cortical : un nuevo modelo experimental para las formas progresivas de la Esclerosis Múltiple
Multiple sclerosis (MS) is a demyelinating, inflammatory and degenerative disease of the central nervous system (CNS) of unknown etiology, which causes irreversible neurological disability in young adults. MS shows different clinical patterns: relapsing-remitting MS (RRMS) and the progressive forms...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2018
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_3142 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_3142.dir/3142.PDF |
| Aporte de: |
| Sumario: | Multiple sclerosis (MS) is a demyelinating, inflammatory and degenerative disease of the central nervous system (CNS) of unknown etiology, which causes irreversible neurological disability in young adults. MS shows different clinical patterns: relapsing-remitting MS (RRMS) and the progressive forms (primary and secondary, PPMS and SPMS respectively) that are characterized by the presence of cortical lesions, which strongly correlates with cognitive impairment and disability. Nowadays, many treatments are available for RRMS, only one for PPMS and none for the SPMS. This situation is mainly due to the fact that the pathogenic mechanisms of the progressive forms are still unknown. In the present work, we developed an animal model of cortical involvement of MS, that reflects the main characteristics of SPMS and PPMS, generated through the chronic expression of interleukin 1B (IL-1B) in the cerebral cortex. The animals showed neuroinflammation, demyelination, glial activation and cortical neurodegeneration, associated with short-term memory impairment and anxiety. We also demonstrated the presence of meningeal inflammation adjacent to the cortical lesions, with similar characteristics to those described in patients with the progressive forms of MS. A peripheral pro-inflammatory stimulation with IL-1B exacerbated these features, which affect the progression of the disease. |
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