Meningeal inflammation correlates with neurodegeneration and glial activation in a chronic cortical focal animal model of Multiple Sclerosis

BERENICE ANABEL SILVA; LEAL, MARÍA CELESTE; MARIA ISABEL FARIAS; FERNANDO J PITOSSI; CARINA C FERRARI

Paris

Congreso; ECTRIMS 2017; 2017

European Committee for Treatment and Research In Multiple Sclerosis

Background: Thepresence of meningeal inflammation was described mainly in progressive forms ofmultiple sclerosis (MS) mostly associate with cortical pathology in animalmodels and patients. Meningeal inflammation isassociated with increased cortical demyelination, neurodegeneration, glialactivation and a more severe disease outcome in MS patients. The aim ofthis work is to characterize the meningeal inflammation associated with focalcortical demyelination and neurodegeneration in chronic cortical focal animalmodel. Methods: Chronic cortical lesions were induced by injecting anadenovector expressing either human IL-1b (AdIL-1) or betagalactosidase (AdBgal) as control in the prefrontal cortex ofadult rats. Systemic inflammation was induced by peripheral injection of eitherAd-IL1b or Adbgal.  The analysis were performed 7 and 30 dayspost peripheral injection (dpi). We performed behavioural, histological,immunohistochemical and electronic microscope. Systemic stimulation was checkedby peripheral blood cells counting.  Results: Peripherally stimulated IL-1binduced cortical lesions exhibited meningeal inflammation characterized byinflammatory infiltrate mostly composed of macrophages, lymphocytes,neutrophils and follicular dendritic cells: CD4 +, CD8+, CD45+RC+, CD20+ cellswere found. Follicular dendritic cells we also observed as CD23+ and CD39+cells in the follicular like structures in the meninges. The number offollicle-like structures positively correlates with microglia and astrogliaactivation and neurodegeneration at both time point studied, 7 and 30 dpi. Conclusions:Meningeal inflammation correlates with cortical damage. We demonstrated thatcortical injury induces meningeal inflammation, but the relationship and theresponsibility of both events on the chronicity of  cortical damage remained stillcontroversial.