title: Stalled cerebral capillary blood flow in mouse models of essential thrombocythemia and polycythemia vera revealed by in vivo two-photon imaging.
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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
authors.forename: T P
authors.initials: TP
authors.lastname: Santisakultarm
authors.forename: C Q
authors.initials: CQ
authors.lastname: Paduano
authors.forename: T
authors.initials: T
authors.lastname: Stokol
authors.forename: T L
authors.initials: TL
authors.lastname: Southard
authors.forename: N
authors.initials: N
authors.lastname: Nishimura
authors.forename: R C
authors.initials: RC
authors.lastname: Skoda
authors.forename: W L
authors.initials: WL
authors.lastname: Olbricht
authors.forename: A I
authors.initials: AI
authors.lastname: Schafer
authors.forename: R T
authors.initials: RT
authors.lastname: Silver
authors.forename: C B
authors.initials: CB
authors.lastname: Schaffer
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D001792:Blood Platelets / Q000166:cytology; D016026:Bone Marrow Transplantation; D002196:Capillaries / Q000378:metabolism; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000166:cytology; D005260:Female; D053614:Janus Kinase 2 / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D009196:Myeloproliferative Disorders; D055095:Optics and Photonics; D017785:Photons; D011086:Polycythemia / Q000097:blood; D011087:Polycythemia Vera / Q000097:blood*; D013920:Thrombocythemia, Essential / Q000097:blood*; D013927:Thrombosis / Q000209:etiology
chemical_list: C507926:Jak2 protein, mouse; D053614:Janus Kinase 2
keywords: animal models; cerebrovascular circulation; microcirculation; myeloproliferative disorders; optical imaging