Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
J Thromb Haemost. 2014 Dec;12(12):2120-30. doi: 10.1111/jth.12738. Epub 2014 Oct 29.
Essential thrombocythemia (ET) and polycythemia vera (PV) are myeloproliferative neoplasms (MPNs) that share the JAK2(V617F) mutation in hematopoietic stem cells, leading to excessive production of predominantly platelets in ET, and predominantly red blood cells (RBCs) in PV. The major cause of morbidity and mortality in PV and ET is thrombosis, including cerebrovascular occlusive disease.
To identify the effect of excessive blood cells on cerebral microcirculation in ET and PV.
We used two-photon excited fluorescence microscopy to examine cerebral blood flow in transgenic mouse models that mimic MPNs.
We found that flow was 'stalled' in an elevated fraction of brain capillaries in ET (18%), PV (27%), mixed MPN (14%) and secondary (non-MPN) erythrocytosis (27%) mice, as compared with controls (3%). The fraction of capillaries with stalled flow increased when the hematocrit value exceeded 55% in PV mice, and the majority of stalled vessels contained only stationary RBCs. In contrast, the majority of stalls in ET mice were caused by platelet aggregates. Stalls had a median persistence time of 0.5 and 1 h in ET and PV mice, respectively. Our findings shed new light on potential mechanisms of neurological problems in patients with MPNs.
原发性血小板增多症（ET）和真性红细胞增多症（PV）是骨髓增殖性肿瘤（MPN），它们在造血干细胞中共享 JAK2（V617F）突变，导致 ET 中主要是血小板过度产生，而 PV 中主要是红细胞（RBC）过度产生。PV 和 ET 发病和死亡的主要原因是血栓形成，包括脑血管阻塞性疾病。
确定过多的血细胞对 ET 和 PV 脑微循环的影响。
我们使用双光子激发荧光显微镜检查模拟 MPN 的转基因小鼠模型的脑血流。
我们发现，与对照组（3%）相比，在 ET（18%）、PV（27%）、混合 MPN（14%）和继发性（非-MPN）红细胞增多症（27%）小鼠中，有一部分脑毛细血管的血流“停滞”。当 PV 小鼠的血细胞比容值超过 55%时，停滞血流的毛细血管比例增加，并且大多数停滞的血管中只含有静止的 RBC。相比之下，ET 小鼠中的大多数停滞是由血小板聚集引起的。停滞的中位持续时间分别为 ET 小鼠 0.5 小时和 PV 小鼠 1 小时。我们的发现为 MPN 患者的神经系统问题的潜在机制提供了新的见解。
