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Stalled cerebral capillary blood flow in mouse models of essential thrombocythemia and polycythemia vera revealed by in vivo two‐photon imaging
Author(s) -
Santisakultarm T. P.,
Paduano C. Q.,
Stokol T.,
Southard T. L.,
Nishimura N.,
Skoda R. C.,
Olbricht W. L.,
Schafer A. I.,
Silver R. T.,
Schaffer C. B.
Publication year - 2014
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12738
Subject(s) - polycythemia vera , essential thrombocythemia , microcirculation , medicine , platelet , hematocrit , flow cytometry , pathology , haematopoiesis , thrombosis , ex vivo , cerebral blood flow , stem cell , immunology , in vivo , biology , microbiology and biotechnology
Summary Background Essential thrombocythemia ( ET ) and polycythemia vera ( PV ) are myeloproliferative neoplasms ( MPN s) that share the JAK 2 V617F mutation in hematopoietic stem cells, leading to excessive production of predominantly platelets in ET , and predominantly red blood cells ( RBC s) 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 MPN s. 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 RBC s. 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 MPN s.