Hosseini Leila, Soltani-Zangbar Mohammad Sadegh, Abolhasanpour Nasrin, Hosseini Maryam, Delkhosh Aref, Dolati Sanam, Mehdizadeh Amir, Athari Seyed Zanyar, Rikhtegar Reza, Alikhaniha Hossein, Babaei Fatemeh, Pirouzpanah Mohammad Bagher, Yousefi Mehdi
Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Immunol Res. 2025 Apr 23;73(1):75. doi: 10.1007/s12026-025-09630-9.
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.
缺血性中风（IS）仍是全球范围内导致死亡和神经功能残疾的主要原因。抗CD20治疗具有强大的抗炎作用。在此，我们研究了抗CD20对大鼠模型中IS诱导的炎症和组织病理学变化的影响。雄性Sprague-Dawley大鼠分为三组：对照组、假手术组和中风组。中风组大鼠在感觉运动皮层区域接受光血栓形成诱导的IS。它们又被分为以下亚组：缺血后用抗CD20治疗，并在IS发生5天和/或10天后处死。通过苏木精和伊红染色评估组织学变化。通过定量实时PCR检测外周血单核细胞中炎症标志物（VIM、ANXA3、SLC22 A4和ADM）的mRNA水平，以及Th1、Th2和Th17亚群的转录因子水平（分别为Tbet、GATA3和ROR-γ），还有Foxp3的水平。IS发生后第5天和第10天，ADM和SLC22 A4的水平升高，而抗CD20治疗使其水平逆转。抗CD20治疗在10天后通过下调VIM和ANXA3减轻了炎症。这种治疗效果主要是由Th1-Th17驱动的炎症反应（Tbet和RORγt）下调以及Th2活性（GATA-3）上调介导的。此外，抗CD20增加了Foxp3的表达。抗CD20治疗在10天后还可减少脑组织损伤。我们的数据表明，炎症和组织病理学改变与IS的光血栓形成模型相关，而抗CD20治疗可减轻炎症并缓解组织病理学变化。
