Corticosterone-Mediated Body Weight Loss Is an Important Catabolic Process for Poststroke Immunity and Survival.
Corticosterone-Mediated Body Weight Loss Is an Important Catabolic Process for Poststroke Immunity and Survival.
复制标题
DOI：
10.1161/strokeaha.119.026053
复制
发表时间：
2019-07
期刊：
影响因子：
8.3
通讯作者：
Jiwon Yang;Eunhee Kim;Cesar D Beltran;Sunghee Cho
中科院分区：
文献类型：
--
作者：
Jiwon Yang;Eunhee Kim;Cesar D Beltran;Sunghee Cho
背景和目的：卒中后急性重度体重减轻与卒中后关键时期的高死亡率相关。然而，一些减少体重减轻的干预措施并不成功。目前，这种非凡的分解代谢过程的生物学意义还没有得到很好的理解。脾源性单核细胞/巨噬细胞（脾源性单核细胞/巨噬细胞）是募集至受损脑的主要免疫细胞。已经证明，运输的脂肪酸是重要的组织修复和恢复。本研究的目的是研究BW减少是否是MM介导的免疫应答对小鼠生存所必需的，以及皮质酮介导的分解代谢事件是否是该过程的基础。方法-C57 BL/6雄性小鼠（12周龄）进行短暂的大脑中动脉闭塞。在中风后小鼠的脾脏、血液和脑中测定BW、总胆红素及其Ly-6Chigh和Ly-6Clow亚群。在肾上腺切除、假肾上腺切除和肾上腺切除补充皮质酮的小鼠中测定卒中后存活率和MM亚群。结果：脑卒中使体重下降，最大降幅出现在卒中后第3天（17.2±5.2%）.在第3天的减少与脾脏中的损伤严重程度和选择性消耗CD 4+细胞呈正相关，但与其他类型的免疫细胞无关。值得注意的是，重度BW降低（第3天≥18%）的小鼠脾脏MM耗竭显著更大。在中度和重度BW损失的动物中，中风在血液中消耗了相似程度的循环脂肪。Ly-6C+单核细胞在中风后脑中的浸润在体重严重损失的小鼠中更大。阻断分解代谢过程肾上腺切除显着增加中风后死亡率，但死亡率部分抢救肾上腺切除小鼠补充皮质酮。结论：脑卒中引起的体重下降促进MM介导的免疫反应，肾上腺皮质酮介导的分解代谢过程是脑卒中后生存所必需的。
Background and Purpose- Stroke-induced acute severe body weight (BW) loss is associated with a high rate of mortality during a critical poststroke period. Several interventions to reduce weight loss, however, have not been successful. Currently, the biological significance of this extraordinary catabolic process is not well understood. Spleen-derived monocytes/macrophages (MMs) are the major immune cells recruited to the injured brain. The trafficking of MMs has been shown to be important for tissue repair and recovery. The purpose of the study is to investigate whether the BW reduction is essential for MM-mediated immune response for mice to survive and whether a corticosterone-mediated catabolic event underlies the processes. Methods- C57BL/6 male mice (12-week-old) were subjected to transient middle cerebral artery occlusion. BW, total MMs, and their Ly-6Chigh and Ly-6Clow subsets were determined in the spleen, blood, and the brain in poststroke mice. Poststroke survival rate and MM subsets were determined in mice with adrenalectomy, sham-adrenalectomy, and adrenalectomy mice supplemented with corticosterone. Results- Stroke reduced BW with a maximum reduction at day 3 poststroke (17.2±5.2%). The reduction at day 3 was positively linked to injury severity and selective depletion of MMs, but no other types of immune cells, in the spleen. Notably, the splenic MM depletion was significantly greater in mice with severe BW reduction (≥18% at day 3). In the blood, stroke depleted circulating MMs to a similar degree in animals with moderate and severe BW loss. Ly-6C+ monocyte infiltration in the poststroke brain was greater in mice with severe BW loss. Blocking the catabolic process by adrenalectomy significantly increased poststroke mortality, but the mortality was partially rescued by corticosterone supplement in adrenalectomy mice. Conclusions- Stroke-induced BW loss facilitates MM-mediated immune response, and the adrenal corticosterone-mediated catabolic process is necessary for poststroke survival.