The effect of anti-CD20 on inflammation and histopathological alternations in rat photothrombotic ischemic stroke model.

Abstract

Ischemic stroke (IS) has remained the main cause of mortality and neurological disabilities worldwide. Anti-CD20 treatments have a potent anti-inflammatory effect. Here, we investigated the effect of anti-CD20 on IS-induced inflammation and histopathologic changes in the rat model. Male Sprague-Dawley rats were divided into three groups: control, sham, and stroke. Rats in the stroke groups underwent photothrombosis-induced IS in the sensorimotor cortex area. They were divided into the following subgroups: treated with anti-CD20 after ischemia and killed after 5 and/or 10 days of IS. Histological changes were assessed by hematoxylin and eosin staining. mRNA levels of inflammation markers (VIM, ANXA3, SLC22 A4, and ADM), and also levels of transcription factors for Th1, Th2, and Th17 subsets (Tbet, GATA3, and ROR-γ, respectively), and also Foxp3 were detected in the peripheral blood mononuclear cells by quantitative real-time PCR. The levels of ADM and SLC22 A4 increased following IS on the 5th and 10th days, while treatment with anti-CD20 reversed their levels. Anti-CD20 therapy attenuated inflammation through down-regulation of VIM and ANXA3 after 10 days. This therapeutic effect was mainly mediated by the downregulation of Th1-Th17-driven inflammatory responses (Tbet and RORγt) and the upregulation of Th2 activities (GATA- 3). In addition, anti-CD20 increased the expression of Foxp3. Anti-CD20 treatment can also reduce brain tissue damage after 10 days. Our data showed that inflammation and histopathological alterations are associated with the photothrombotic model of IS, while treatment with anti-CD20 could reduce inflammation and alleviate histopathological changes.