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Cerebral Vasculature (cerebral + vasculature)
Selected AbstractsProinflammatory phenotype with imbalance of KLF2 and RelA: Risk of childhood stroke with sickle cell anemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2010Judy Enenstein Altered inflammation signaling within the cerebral vasculature may be an important risk factor for stroke in children with sickle cell anemia (SCA). This study examines how differential expression of NF,B/p65 (RelA), KLF2, and other transcription factors may act as switches in inflammation signaling leading to observed differences between non-SCA (NS) African Americans and African Americans with SCA who are either at risk (AR) or not at risk (NAR) of childhood stroke based on occurrence of Circle of Willis disease. Clover/Transfac analysis was used to identify overrepresented transcription factor binding motifs on genes associated with inflammation. Transcription factor binding motifs for the NF,B family and RFX1 were overrepresented on inflammation signaling gene set analysis. Variations in protein expression were determined by flow cytometry of blood outgrowth endothelial cells (BOECs) from NS, AR, and NAR donors and Western blots of protein extracts from both unstimulated and TNF,/IL1,-stimulated BOECs. BOECs from patients with SCA had more cytoplasmic-derived RelA compared with NS BOECs. Sickle BOECs also had heightened responses to inflammatory stimuli compared with NS BOECs, as shown by increased nuclear RelA, and intracellular adhesion molecule (ICAM) response to TNF,/IL1, stimulation. Multiple control points in RelA signaling were associated with risk of childhood stroke. The ratio of proinflammatory factor RelA to anti-inflammatory factor KLF2 was greater in BOECs from AR donors than NS donors. Group risk of childhood stroke with SCA was greatest among individuals who exhibited increased expression of proinflammatory transcription factors and decreased expression of transcription factors that suppress inflammation. Am. J. Hematol. 2010. © 2009 Wiley-Liss, Inc. [source] Cerebral developmental venous anomalies: Current concepts,ANNALS OF NEUROLOGY, Issue 3 2009Diego San Millán Ruíz MD Cerebral developmental venous anomalies are the most frequently encountered cerebral vascular malformation, and as such, are frequently reported as fortuitous findings in computed tomography (CT) and magnetic resonance imaging (MRI) studies. Developmental venous anomalies (DVAs) are generally considered extreme anatomical variations of the cerebral vasculature, and follow a benign clinical course in the vast majority of cases. Here we review current concepts on DVAs with the aim of helping clinicians understand this complex entity. Morphological characteristics that are necessary to conceptualize DVAs are discussed in depth. Images modalities used in diagnosing DVAs are reviewed, including new MRI or CT techniques. Clinical presentation, association with other vascular malformations and cerebral parenchymal abnormalities, and possible physiopathological processes leading to associated imaging or clinical findings are discussed. Atypical forms of DVAs are also reviewed and their clinical significance discussed. Finally, recommendations as to how to manage asymptomatic or symptomatic patients with a DVA are advanced. Ann Neurol 2009;66:271,283 [source] Cerebrospinal fluid amyloid ,40 is decreased in cerebral amyloid angiopathy,ANNALS OF NEUROLOGY, Issue 2 2009Marcel M. Verbeek MSc Cerebral amyloid angiopathy is caused by deposition of the amyloid , protein in the cerebral vasculature. In analogy to previous observations in Alzheimer disease, we hypothesized that analysis of amyloid ,40 and ,42 proteins in the cerebrospinal fluid might serve as a molecular biomarker. We observed strongly decreased cerebrospinal fluid amyloid ,40 (p < 0.01 vs controls or Alzheimer disease) and amyloid ,42 concentrations (p < 0.001 vs controls and p < 0.05 vs Alzheimer disease) in cerebral amyloid angiopathy patients. The combination of amyloid ,42 and total tau discriminated cerebral amyloid angiopathy from controls, with an area under the receiver operator curve of 0.98. Our data are consistent with neuropathological evidence that amyloid ,40 as well as amyloid ,42 protein are selectively trapped in the cerebral vasculature from interstitial fluid drainage pathways that otherwise transport amyloid , proteins toward the cerebrospinal fluid. Ann Neurol 2009;66:245,249 [source] SYMPOSIUM: Clearance of A, from the Brain in Alzheimer's Disease: A,-Degrading Enzymes in Alzheimer's DiseaseBRAIN PATHOLOGY, Issue 2 2008James Scott Miners Abstract In Alzheimer's disease (AD) A, accumulates because of imbalance between the production of A, and its removal from the brain. There is increasing evidence that in most sporadic forms of AD, the accumulation of A, is partly, if not in some cases solely, because of defects in its removal,mediated through a combination of diffusion along perivascular extracellular matrix, transport across vessel walls into the blood stream and enzymatic degradation. Multiple enzymes within the central nervous system (CNS) are capable of degrading A,. Most are produced by neurons or glia, but some are expressed in the cerebral vasculature, where reduced A,-degrading activity may contribute to the development of cerebral amyloid angiopathy (CAA). Neprilysin and insulin-degrading enzyme (IDE), which have been most extensively studied, are expressed both neuronally and within the vasculature. The levels of both of these enzymes are reduced in AD although the correlation with enzyme activity is still not entirely clear. Other enzymes shown capable of degrading A,in vitro or in animal studies include plasmin; endothelin-converting enzymes ECE-1 and -2; matrix metalloproteinases MMP-2, -3 and -9; and angiotensin-converting enzyme (ACE). The levels of plasmin and plasminogen activators (uPA and tPA) and ECE-2 are reported to be reduced in AD. Reductions in neprilysin, IDE and plasmin in AD have been associated with possession of APOE,4. We found no change in the level or activity of MMP-2, -3 or -9 in AD. The level and activity of ACE are increased, the level being directly related to A, plaque load. Up-regulation of some A,-degrading enzymes may initially compensate for declining activity of others, but as age, genetic factors and diseases such as hypertension and diabetes diminish the effectiveness of other A,-clearance pathways, reductions in the activity of particular A,-degrading enzymes may become critical, leading to the development of AD and CAA. [source] The Role of Cystatin C in Cerebral Amyloid Angiopathy and Stroke: Cell Biology and Animal ModelsBRAIN PATHOLOGY, Issue 1 2006Efrat Levy A variant of the cysteine protease inhibitor, cystatin c, forms amyloid deposited in the cerebral vasculature of patients with hereditary cerebral hemorrhage with amyloidosis, icelandic type (hchwa-i), leading to cerebral hemorrhages early in life. however, cystatin c is also implicated in neuronal degenerative diseases in which it does not form the amyloid protein, such as alzheimer disease (ad). accumulating data suggest involvement of cystatin c in the pathogenic processes leading to amyloid deposition in cerebral vasculature and most significantly to cerebral hemorrhage in patients with cerebral amyloid angiopathy (caa). This review focuses on cell culture and animal models used to study the role of cystatin c in these processes. [source] | ||||||||||