The effects of bone marrow derived macrophages on ischemic brain damage

脑缺血会引发急性炎症，从而加剧原发性脑损伤。先天免疫系统的激活是这种炎症反应的重要组成部分。炎症是通过促炎细胞因子的作用发生的。这些细胞因子的产生是通过toll样受体（TLRs）的信号传导启动的。其中，TLR4主要识别脂多糖（LPS），越来越多的证据表明TLR4在脑缺血的协调机制中起着至关重要的作用。在本研究中，我们研究了靶向破坏TLR4对缺血性脑损伤严重程度的影响。TLR4消融在再灌注后1天显著降低梗死面积。在缺乏TLR4的情况下，组织损伤的改善强调了先天免疫在缺血性脑损伤表现中的重要性。此外，TLR4消融骨髓源性巨噬细胞可显著降低梗死面积。这些结果表明，骨源性巨噬细胞是缺血性脑损伤的重要调节剂。

Cerebral ischemia triggers acute inflammation, which exacerbates primary brain damage. Activation of the innate immune system is an important component of this inflammatory response. Inflammation occurs through the action of proinflammatory cytokines. Production of these cytokines is initiated by signaling through Toll-like receptors (TLRs). Among them, TLR4 recognizes primarily lipopolysaccharide (LPS) and an increasing evidence points that TLR4 plays a crucial role in the concert mechanism of the cerebra ischemia. In this study, we investigated the effect of targeted disruption of TLR4 on the severity of ischemic brain injury. TLR4 ablation significantly decreased infarct size at 1 day after reperfusion. The amelioration of tissue damage in the absence of TLR4 underscores the importance of innate immunity for the manifestation of ischemic brain injury. Furthermore, TLR4 ablation in the bone marrow derived macrophage significantly decreased infarct size. These results indicate that bone barrow derived macrophages are an important modulator of ischemic brain injury.