Several hundred microRNAs (miRNAs) have recently been cloned from a wide range of organisms across phylogeny. Despite the high degree of conservation of miRNAs, their functions in general, and in mammals particularly, are just beginning to be defined. Here we show that an oligonucleotide DNA array can be successfully used for the simultaneous analysis of miRNA expression profiles from tissues or cells. From a subset of miRNAs expressed in the brain we designed an oligonucleotide array spotted with probes specific for 44 mature miRNAs. These arrays demonstrated precise regulation of miRNA expression at mammalian brain developmental epochs. About 20% of the probed miRNAs changed significantly in their expression during normal brain development, and two of them, miR-9 and miR-131, were dysregulated in presenilin-1 null mice exhibiting severe brain developmental defects. Transcripts with regulated expression patterns on the arrays were validated by Northern blots. Additionally, a bioinformatic analysis of developmentally regulated miRNAs suggested potential mRNA targets. The arrays also revealed miRNAs distributed to translating polyribosomes in primary neurons where they are likely to modulate translation. Therefore, oligonucleotide arrays provide a new tool for studying miRNA expression in a variety of biological and pathobiological settings. Creating clusters of coexpressed miRNAs will contribute to understanding their regulation, functions, and discovery of mRNA targets.

The no-reflow phenomenon refers to the observation that when an organ is made ischemic by occlusion of a large artery supplying it, restoration of patency in that artery does not restore perfusion to the microvasculature supplying the parenchyma of that organ. This has been observed after prolonged arterial occlusions in the heart (30–90 min), brain, skin, and kidney. In experimental models, zones of no reflow in the heart are characterized by ultrastructural microvascular damage, including focal endothelial swelling obstructing the lumen of small vessels. Blood elements such as neutrophil plugs, platelets, and stacking of erythrocytes have also been implicated. No reflow is associated with poor healing of the myocardial infarction. In patients, no reflow is associated with a poor clinical outcome independent of infarct size, suggesting that therapy for no reflow may be an important approach to improving outcome for ST elevation myocardial infarction. No reflow occurs after reperfusion of experimental cerebral ischemia and may be observed after only 5-min episodes of ischemia. Aggregation of blood elements may play a greater role than in cardiac no reflow. No reflow in the brain may involve cortical spreading depression with disturbed local vascular control and high, vasculotonic levels of extracellular K⁺ concentration, postischemic swelling in endothelial cells and abutting end feet of pericytes, pericyte contraction and death, interstitial edema with collapse of cerebral capillaries, and inflammatory reaction. New guidelines suggesting that reperfusion for stroke may be considered as late as 24 h after the onset of symptoms suggest that clinicians may be seeing more no reflow in the future.

Introduction: T1‐ and T2‐weighted sequences from MRI often provide useful complementary information about tissue properties. Leukoaraiosis results in signal abnormalities on T1‐weighted images, which are automatically quantified by FreeSurfer, but this marker is poorly characterized and is rarely used. We evaluated associations between white matter hyperintensity (WM‐hyper) volume from FLAIR and white matter hypointensity (WM‐hypo) volume from T1‐weighted images and compared their associations with age and cerebrospinal fluid (CSF) β‐amyloid and tau.Methods: A total of 56 nondemented participants (68–94 years) were recruited and gave informed consent. All participants went through MR imaging on a GE 1.5T scanner and of these 47 underwent lumbar puncture for CSF analysis. WM‐hypo was calculated using FreeSurfer analysis of T1 FSPGR 3D, and WM‐hyper was calculated with the Lesion Segmentation Toolbox in the SPM software package using T2‐FLAIR.Results: WM‐hyper and WM‐hypo were strongly correlated (r = .81; parameter estimate (p.e.): 1.53 ± 0.15; p < .0001). Age was significantly associated with both WM‐hyper (r = .31, p.e. 0.078 ± 0.030, p = .013) and WM‐hypo (r = .42, p.e. 0.055 ± 0.015, p < .001). CSF β‐amyloid levels were predicted by WM‐hyper (r = .33, p.e. −0.11 ± 0.044, p = .013) and WM‐hypo (r = .42, p.e. −0.24 ± 0.073, p = .002). CSF tau levels were not correlated with either WM‐hyper (p = .9) or WM‐hypo (p = .99).Conclusions: Strong correlations between WM‐hyper and WM‐hypo, and similar associations with age, abnormal β‐amyloid, and tau suggest a general equivalence between these two imaging markers. Our work supports the equivalence of white matter hypointensity volumes derived from FreeSurfer for evaluating leukoaraiosis. This may have particular utility when T2‐FLAIR is low in quality or absent, enabling analysis of older imaging data sets.

Brain atrophy remains an ominous and incompletely understood consequence of aging. Magnetic resonance (MR) imaging of the brain in cross-sectional and longitudinal cohort investigations has demonstrated that brain atrophy is a sensitive indicator of mild cognitive impairment and dementia. Whole-brain atrophy, and hippocampus atrophy in particular, is greater in individuals with Alzheimer disease compared with healthy aged control subjects.^1-3 Findings from studies^4-6 of individuals at risk for familial Alzheimer disease suggest that atrophy of certain brain regions may precede the generalized cerebral atrophy seen at the time of diagnosis. The mechanisms that underlie accelerated global and regional brain atrophy are incompletely understood.

Cardiovascular magnetic resonance (CMR) has been validated for the noninvasive assessment of total arterial compliance and aortic stiffness, but their associations with cardiovascular outcomes is unknown. The purpose of this study was to evaluate associations of CMR measures of total arterial compliance and two CMR measures of aortic stiffness with respect to future cardiovascular events.