Pharmacologic or genetic inhibition of EphB3 receptor kinase impacts CNS pathology during progressive EAE

We evaluated the role of EphB3 on the regulation of astrocyte and microglial responses and its potential as a therapeutic target during progressive EAE. We induced EAE in NOD mice that will develop a progressive form of the disease. Starting at the beginning of the progressive phase, A38 was administered and alternatively EphB3 was KD in astrocytes. Both treatments ameliorated the EAE. The transcriptional analysis of astrocytes and microglia revealed the decreased expression of genes associated to inflammation and neurodegeneration in both conditions. Astrocytes and microglia were isolated from CNS of mice undergoing progressive model of EAE and which have been intrathecally injected with lentviral vectors either ctrl, or shEphB3 astrocyte specific. shCtrl were additionally treated with A38 or the vehicle as control.