Variations and morphometric analysis of the proximal segment of the superior cerebellar artery

Introduction The superior cerebral artery is a clinically significant vessel, but little is known about its radiological anatomy. The aim of this study was to describe the anatomical variations of the proximal segment of the superior cerebellar artery using Computed Tomography Angiography. Materials and methods The study group consisted of 200 subjects (54.5% female, mean age±SD 56.2±17.2 years) that had undergone head Computed Tomography Angiography. Subjects with any intracranial pathologies were excluded. Images in Maximum Intensity Projections were used to study the anatomical anomalies of the superior cerebellar artery. Results In 200 subject 388 superior cerebellar arteries were found. Twelve (3.09%) SCAs were duplicated in 11 patients and all originated from the basilar artery. In 8 (4.00%) patients the superior cerebellar artery was absent. The origin of the SCA was most often bilateral, mainly from the basilar artery (76.29%). The superior cerebellar artery diameter, measured at the site of the origin, was statistically significantly different depending on the place of the origin: wider when originating from the basilar artery as a single vessel (1.48±0.42mm vs. 1.34±0.52mm; p=0.03) and narrower when originating as duplicated one (1.38±0.48mm vs. 1.46±0.44mm; p=0.55). Conclusion Superior cerebellar artery usually originates bilaterally from the basilar artery as a single trunk. Its diameter is significantly wider in that type in comparison to other anatomical variations

Trisomy 21 enhances human fetal erythro-megakaryocytic development

Children with Down syndrome exhibit 2 related hematopoietic diseases: transient myeloproliferative disorder (TMD) and acute megakaryoblastic leukemia (AMKL). Both exhibit clonal expansion of blasts with biphenotypic erythroid and megakaryocytic features and contain somatic GATA1 mutations. While altered GATA1 inhibits erythro-megakaryocytic development, less is known about how trisomy 21 impacts blood formation, particularly in the human fetus where TMD and AMKL originate. We used in vitro and mouse transplantation assays to study hematopoiesis in trisomy 21 fetal livers with normal GATA1 alleles. Remarkably, trisomy 21 progenitors exhibited enhanced production of erythroid and megakaryocytic cells that proliferated excessively. Our findings indicate that trisomy 21 itself is associated with cell-autonomous expansion of erythro-megakaryocytic progenitors. This may predispose to TMD and AMKL by increasing the pool of cells susceptible to malignant transformation through acquired mutations in GATA1 and other cooperating genes

Platelet factor 4 regulates megakaryopoiesis through low-density lipoprotein receptor–related protein 1 (LRP1) on megakaryocytes

Platelet factor 4 (PF4) is a negative regulator of megakaryopoiesis, but its mechanism of action had not been addressed. Low-density lipoprotein (LDL) receptor–related protein-1 (LRP1) has been shown to mediate endothelial cell responses to PF4 and so we tested this receptor's importance in PF4's role in megakaryopoiesis. We found that LRP1 is absent from megakaryocyte-erythrocyte progenitor cells, is maximally present on large, polyploidy megakaryocytes, and near absent on platelets. Blocking LRP1 with either receptor-associated protein (RAP), an antagonist of LDL family member receptors, or specific anti-LRP1 antibodies reversed the inhibition of megakaryocyte colony growth by PF4. In addition, using shRNA to reduce LRP1 expression was able to restore megakaryocyte colony formation in bone marrow isolated from human PF4-overexpressing mice (hPF4High). Further, shRNA knockdown of LRP1 expression was able to limit the effects of PF4 on megakaryopoiesis. Finally, infusion of RAP into hPF4High mice was able to increase baseline platelet counts without affecting other lineages, suggesting that this mechanism is important in vivo. These studies extend our understanding of PF4's negative paracrine effect in megakaryopoiesis and its potential clinical implications as well as provide insights into the biology of LRP1, which is transiently expressed during megakaryopoiesis