期刊
FRONTIERS IN NEUROLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fneur.2019.00871
关键词
sickle cell disease; stroke; silent cerebral infarction; cerebral hemodynamics; vascular instability; anemia; oxygen extraction fraction; cerebrovascular reserve
资金
- Action Medical Research [GN2509]
- Great Ormond Street Children's Charity [V4615]
- Children with Cancer UK [CwCUK-15-203]
- National Institute for Health Research (UK) [PB-PG1112-29099]
- National Heart, Lung, and Blood Institute (USA) [R01HL079937]
- NIHR Great Ormond Street Hospital Biomedical Research Center
It is well-established that patients with sickle cell disease (SOD) are at substantial risk of neurological complications, including overt and silent stroke, microstructural injury, and cognitive difficulties. Yet the underlying mechanisms remain poorly understood, partly because findings have largely been considered in isolation. Here, we review mechanistic pathways for which there is accumulating evidence and propose an integrative systems-biology framework for understanding neurological risk. Drawing upon work from other vascular beds in SOD, as well as the wider stroke literature, we propose that macro-circulatory hyper-perfusion, regions of relative micro-circulatory hypo-perfusion, and an exhaustion of cerebral reserve mechanisms, together lead to a state of cerebral vascular instability. We suggest that in this state, tissue oxygen supply is fragile and easily perturbed by changes in clinical condition, with the potential for stroke and/or microstructural injury if metabolic demand exceeds tissue oxygenation. This framework brings together recent developments in the field, highlights outstanding questions, and offers a first step toward a linking pathophysiological explanation of neurological risk that may help inform future screening and treatment strategies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据