Globally, stroke is a leading cause of death and disability. Traditional risk factors like hypertension, diabetes, and obesity do not fully account for all stroke cases. Recent infection is regarded as changes in systemic immune signaling, which can increase thrombosis formation and other stroke risk factors. We have previously shown that administration of lipopolysaccharide (LPS) 30-minutes prior to stroke increases in infarct volume. In the current study, we found that animals intermittently exposed to LPS have larger cortical infarcts when compared to saline controls. To elucidate the mechanism behind this phenomenon, several avenues were investigated. We observed significant upregulation of tumor necrosis factor-alpha (TNF-α) mRNA, especially in the ipsilateral hemisphere of both saline and LPS exposed groups compared to sham surgery animals. We also observed significant reductions in expression of genes involved in autophagy in the ipsilateral hemisphere of LPS stroke animals. In addition, we assessed DNA methylation of autophagy genes and observed a significant increase in the ipsilateral hemisphere of LPS stroke animals. Intermittent exposure to LPS increases cortical infarct volume, downregulates autophagy genes, and induces hypermethylation of the corresponding CpG islands. These data suggest that intermittent immune activation may deregulate epigenetic mechanisms and promote neuropathological outcomes after stroke.

在全球范围内，中风是导致死亡和残疾的主要原因。高血压、糖尿病和肥胖等传统危险因素并不能完全解释所有中风病例。最近的感染被认为是全身免疫信号的变化，这会增加血栓形成和其他中风危险因素。我们之前已经表明，在中风前 30 分钟给予脂多糖 (LPS) 会增加梗塞体积。在目前的研究中，我们发现与生理盐水对照组相比，间歇性暴露于 LPS 的动物具有更大的皮质梗塞。为了阐明这种现象背后的机制，研究了几种途径。与假手术动物相比，我们观察到肿瘤坏死因子-α (TNF-α) mRNA 显着上调，特别是在盐水和 LPS 暴露组的同侧半球。我们还观察到 LPS 中风动物同侧半球中参与自噬的基因表达显着降低。此外，我们评估了自噬基因的 DNA 甲基化，并观察到 ​​LPS 中风动物同侧半球的显着增加。间歇性暴露于 LPS 会增加皮质梗死体积，下调自噬基因，并诱导相应 CpG 岛的高甲基化。这些数据表明，间歇性免疫激活可能会放松表观遗传机制并促进中风后的神经病理学结果。我们评估了自噬基因的 DNA 甲基化，并观察到 ​​LPS 中风动物的同侧半球显着增加。间歇性暴露于 LPS 会增加皮质梗死体积，下调自噬基因，并诱导相应 CpG 岛的高甲基化。这些数据表明，间歇性免疫激活可能会放松表观遗传机制并促进中风后的神经病理学结果。我们评估了自噬基因的 DNA 甲基化，并观察到 ​​LPS 中风动物的同侧半球显着增加。间歇性暴露于 LPS 会增加皮质梗死体积，下调自噬基因，并诱导相应 CpG 岛的高甲基化。这些数据表明，间歇性免疫激活可能会放松表观遗传机制并促进中风后的神经病理学结果。