Influence of the innate immune system in a model of cortical inflammation as an approach to the progressive forms of multiple sclerosis

International Congress on Neuroimmunology and Therapeutics

DoubleTree by Hilton Hotel San Francisco Airport, San Francisco, CA, USA

Carina Cintia Ferrari

Posters-Accepted Abstracts: J Neurol Disord

Abstract :

Multiple Sclerosis (MS) is a neurodegenerative disease characterized by repeated inflammatory events, demyelination and axonal damage, along with loss of function. MS exhibited different forms: relapsing remitting (RRMS), primary and secondary progressive (PPMS, SPMS). Even though neuroinflammation is hallmark in every form of the disease, immunomoduladory treatments are beneficial in the early stages of MS, but ineffective in PPMS and SPMS. Recently, cortical lesions were described in PPMS and SPMS patients, which contribute to physical disability and cognitive impairment that characterize the progressive forms. The pathogenesis of cortical lesions is still unknown. Therefore, the cortical microenvironment could influence the degree of inflammation, tissue damage and the repair of the lesions. We developed a model of chronic and focal inflammatory triggered by the long term expression of one inflammatory cytokine, interleukin-1beta (IL-1b). Additionally, regional differences to the long term expression of IL-1b, were found between striatum and Substantia nigra. The aim of this work is to study the effect of the chronic expression of IL-1 in the cortex of adult rats and the effect of peripheral pro-inflammatory stimulus on these lesions. We used an adenovector expressing humanIL-1b (AdIL-1b) or beta-galactosidase (Adbgal) to induce chronic expression in the cortex. We performed behavioral, histological, immunohistochemical and molecular analysis. The long term expression of IL-1 in the cortex induces inflammation characterized by neutrophil recruitment and edema, neurodegeneration, and astro and microglia activation. The inflammation peaked at 15-21 days post injection and the lesion is restored by 30 days after injection. These results are correlated with a worse performance in the behavioral test of novel object recognition of IL-1 injected animals at the peak of inflammation (15-21 days), which is improved as far as the lesion is recovered (30 days). Additionally, systemic peripheral stimulation exacerbates the cortical lesion, with an increased inflammatory and glial response. In conclusion, we developed an experimental model of cortical inflammation and cognitive deterioration. The details of the pathophysiology of the progressive MS need to be better understood. A simple animal model allows the analysis of individual components of MS pathology, which could be use as targets for designing specific progressive MS treatments.