Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA.
University of Connecticut Health Science Center, Farmington, Connecticut, USA.
Neurobiol Aging. 2018 Jan;61:102-111. doi: 10.1016/j.neurobiolaging.2017.09.022. Epub 2017 Sep 28.
Elderly stroke patients and aged animals subjected to experimental stroke have significantly worse functional recovery and higher mortality compared to younger subjects. Activation of the peripheral immune system is known to influence stroke outcome. Prior studies have shown that splenectomy reduces ischemic brain injury in young mice. As immune function changes with aging, it is unclear whether splenectomy will confer similar benefits in aged animals. We investigated the contribution of spleen to brain injury after cerebral ischemia in aged male mice. Splenic architecture and immune cell composition were altered in aged mice. Splenectomy 2 weeks before stroke resulted in improved neurobehavioral and infarct outcomes in aged male mice. In addition, there was a reduction in peripheral immune cell infiltration into the brain and decreased levels of peripheral inflammatory cytokines after stroke in aged splenectomized mice. Splenectomy immediately after reperfusion also improved behavioral and infarct outcomes. This study suggests that inhibition of the splenic immune response is a translationally relevant target to pursue for stroke treatment in aged individuals.
与年轻受试者相比，老年中风患者和接受实验性中风的老年动物的功能恢复明显较差，死亡率更高。外周免疫系统的激活已知会影响中风的结果。先前的研究表明，脾切除术可减少年轻小鼠的缺血性脑损伤。由于免疫功能随年龄而变化，尚不清楚脾切除术是否会为老年动物带来类似的益处。我们研究了脾脏对年老雄性小鼠脑缺血后脑损伤的贡献。年老小鼠的脾脏结构和免疫细胞组成发生改变。中风前 2 周行脾切除术可改善年老雄性小鼠的神经行为学和梗死结局。此外，在老年脾切除小鼠中风后，外周免疫细胞浸润大脑减少，外周炎性细胞因子水平降低。再灌注后立即行脾切除术也可改善行为学和梗死结局。本研究表明，抑制脾脏免疫反应是针对老年个体中风治疗的一个有转化意义的靶点。
