Taylor Roslyn A, Hammond Matthew D, Ai Youxi, Sansing Lauren H
Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut, United States of America; Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, United States of America; Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut, United States of America.
PLoS One. 2014 Dec 3;9(12):e114472. doi: 10.1371/journal.pone.0114472. eCollection 2014.
Intracerebral hemorrhage is a subset of stroke for which there is no specific treatment. The Ly6Chi CCR2+ monocytes have been shown to contribute to acute injury after intracerebral hemorrhage. The other murine monocyte subset expresses CX3CR1 and lower Ly6C levels, and contributes to repair in other disease models. We hypothesized that the Ly6Clo CX3CR1+ monocytes would contribute to recovery after intracerebral hemorrhage. Intracerebral hemorrhage was modeled by blood injection in WT and CX3CR1-null bone marrow chimeras. Neurological outcomes and leukocyte recruitment were quantified at various time points. Functional outcomes were equal at 1, 3, 7, and 14 days after intracerebral hemorrhage in both genotypes. No differences were observed in leukocyte recruitment between genotypes on either 3 or 7 days after intracerebral hemorrhage. A few hundred Ly6Clo monocytes were found in the ipsilateral hemisphere in each genotype and they did not change over time. Peripherally derived CX3CR1+ monocytes were observed in the perihematomal brain 7 and 14 days after intracerebral hemorrhage. Our data suggests CX3CR1 signaling on monocytes does not play an influential role in acute injury or functional recovery after intracerebral hemorrhage and therefore CX3CR1 is not a therapeutic target to improve outcome after intracerebral hemorrhage.
脑出血是中风的一种类型，目前尚无特效治疗方法。已证实Ly6Chi CCR2+单核细胞会导致脑出血后的急性损伤。另一种小鼠单核细胞亚群表达CX3CR1且Ly6C水平较低，在其他疾病模型中有助于修复。我们推测Ly6Clo CX3CR1+单核细胞会有助于脑出血后的恢复。通过向野生型和CX3CR1基因敲除的骨髓嵌合体小鼠注射血液来模拟脑出血。在不同时间点对神经功能结局和白细胞募集情况进行量化。两种基因型小鼠在脑出血后1天、3天、7天和14天的功能结局相同。脑出血后3天和7天，两种基因型小鼠在白细胞募集方面未观察到差异。在每种基因型小鼠的同侧半球均发现了数百个Ly6Clo单核细胞，且其数量未随时间变化。脑出血后7天和14天，在血肿周围脑组织中观察到外周来源的CX3CR1+单核细胞。我们的数据表明，单核细胞上的CX3CR1信号在脑出血后的急性损伤或功能恢复中不起重要作用，因此CX3CR1不是改善脑出血后结局的治疗靶点。
