Chronic colitis induces meninges traffic of gut-derived T cells, unbalances M1 and M2 microglia/macrophage and increases ischemic brain injury in mice

Ischemic stroke is one of the most common diseases leading to death and is the primary cause of physical handicap. Recent studies have reported that chronic colitis increases the risk of ischemic stroke, but it is unknown whether chronic colitis participates in ischemic brain injury directly. A combined mouse model of chronic colitis induced by dextran sodium sulfate (DSS) and ischemic stroke induced by photochemical infarction was used in this study. We demonstrated that chronic colitis significantly increased the infarction volume, activated microglia/macrophage numbers, proliferation of M1 microglia/macrophage, non-gut-derived CD4 + T lymphocyte penetration and decreased neuron numbers in the peri-infarction at 7 d after stroke. Furthermore, gut derived CD4 + T cell accumulation on the meninges was observed at 7 d after stroke. In addition, selective depletion of meningeal macrophages resulted in a reduction of infarction volume and the non-gut-derived CD4 + T lymphocyte penetration. We concluded that chronic colitis exacerbated ischemic stroke by promoting CD4 + T cell migration from the gut to the meninges and disequilibrium of M1 and M2 microglia/macrophages. We speculated that the gut-derived CD4 + T cells may interact with meningeal macrophages and result in non-gut derived CD4 + T lymphocyte infiltration that aggravated brain injury in ischemic stroke.

缺血性脑卒中是导致死亡的最常见疾病之一，也是身体残疾的主要原因。近期研究报道慢性结肠炎会增加缺血性脑卒中的风险，但慢性结肠炎是否直接参与缺血性脑损伤尚不清楚。本研究采用葡聚糖硫酸钠（DSS）诱导的慢性结肠炎和光化学梗死诱导的缺血性脑卒中联合小鼠模型。我们发现，在脑卒中后7天，慢性结肠炎显著增加了梗死体积，激活的小胶质细胞/巨噬细胞数量、M1型小胶质细胞/巨噬细胞的增殖、非肠道来源的CD4 + T淋巴细胞浸润增加，梗死周围神经元数量减少。此外，在脑卒中后7天观察到肠道来源的CD4 + T细胞在脑膜上聚集。另外，选择性清除脑膜巨噬细胞导致梗死体积减小以及非肠道来源的CD4 + T淋巴细胞浸润减少。我们得出结论，慢性结肠炎通过促进CD4 + T细胞从肠道向脑膜迁移以及M1和M2型小胶质细胞/巨噬细胞的失衡，加剧了缺血性脑卒中。我们推测肠道来源的CD4 + T细胞可能与脑膜巨噬细胞相互作用，导致非肠道来源的CD4 + T淋巴细胞浸润，从而加重缺血性脑卒中的脑损伤。