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Chronic hemolysis in SCD causes decreased nitric oxide availability, which may lead to oxidative http://www.selleck.cn/products/Erlotinib-Hydrochloride.html damage of vessels. Chronic inflammation in SCD causes increased leukocyte activation, which may also lead to endothelial damage. Finally, damage to arterial walls from high blood flow velocity due to anemia may cause noninflammatory intimal hyperplasia of intracranial arteries, leading to progressive vascular stenosis, establishing a focus for thrombosis, infarction, and overt stroke [5, 6]. The role of cerebral vasculopathy in the development of SI is still unclear. One hypothesis is that stenosis of medium to large cerebral vessels may set up hemodynamic conditions in which perfusion to distal microvascular beds is impaired, leading to neuronal death around affected microvasculature. This theory may be supported by the finding that http://www.selleckchem.com/products/MK-2206.html those with elevated transcranial Doppler ultrasound (TCD) velocities (representing stenosis of medium to large cerebral vessels) and previous SI have a high risk of developing new or progressive SI [1]. Prophylaxis with regular, chronic erythrocyte transfusions (CTX) for cerebral vascular accident (CVA) prevention is currently recommended for children found to have abnormally high mean blood flow velocities in either the proximal middle cerebral artery or distal internal carotid artery as measured by TCD (termed primary CVA prophylaxis) [7] and in patients who have suffered from an overt CVA (termed secondary CVA prophylaxis). Overall, CTX for primary and secondary CVA prophylaxis reduces the relative risk of stroke in both groups by 85% [8]. Few studies have evaluated the longitudinal effects of primary and secondary CVA prophylaxis on SI or vasculopathy in SCD. There is a paucity of data on the effect of CTX on SI incidence, though a multi-center trial is currently being conducted [15]. Older studies have reported inconsistent findings on the effects of CTX on vasculopathy [3, 5, 9�C12], while more recent work seems to suggest that CTX does not prevent progressive cerebrovascular disease [13, 14]. Thus, we retrospectively examined the prevalence and incidence of SI and changes in radiological cerebral vasculopathies in a cohort of SCD patients on primary or http://www.selleckchem.com/products/ABT-263.html secondary stroke prophylaxis who had serial surveillance MRI and magnetic resonance angiography (MRA) of the brain. Seventeen patients met inclusion criteria, with eight patients on primary stroke prophylaxis and nine patients on secondary stroke prophylaxis. There were nine males and eight females, with a mean patient age of 15 years (range: 6�C23 years). The median follow-up for each patient was 1,184 days (3.2 years), with a mean of 1,580 days (4.3 years �� 3.9), and a range of 275 to 5,819 days. A total of 73.83 patient-years were available for analysis, with an average of 2.7 MRI/MRA studies per patient (range 2�C6). The average time interval between the first and last MRI/MRA was 4.3 years. Table I outlines the MRI and MRA findings of the 17 patients.