Stalled cerebral capillary blood flow in mouse models of essential thrombocythemia and polycythemia vera revealed by in vivo two-photon imaging. Academic Article uri icon

Overview

abstract

  • BACKGROUND: 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. OBJECTIVES: To identify the effect of excessive blood cells on cerebral microcirculation in ET and PV. METHODS: We used two-photon excited fluorescence microscopy to examine cerebral blood flow in transgenic mouse models that mimic MPNs. RESULTS AND CONCLUSIONS: 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.

publication date

  • October 29, 2014

Research

keywords

  • Cerebrovascular Circulation
  • Polycythemia Vera
  • Thrombocythemia, Essential

Identity

Scopus Document Identifier

  • 84916631996

Digital Object Identifier (DOI)

  • 10.1111/jth.12738

PubMed ID

  • 25263265

Additional Document Info

volume

  • 12

issue

  • 12