No abstract

One hundred and six saccular MCA aneurysms (43, ruptured; 63, unruptured) diagnosed with 3-dimensional rotational angiography were analyzed. The patient-specific geometries were reconstructed from 3-dimensional rotational angiography images. Computational fluid dynamics simulations were performed under pulsatile flow conditions driven from typical blood-flow waveforms of the common carotid artery in normal humans, 3 and the following hemodynamic parameters were calculated: wall shear stress (WSS), normalized WSS (NWSS), 2 oscillatory shear index (OSI), 4 WSS gradient (WSSG), 5 gradient oscillatory number, 6 and aneurysm-formation indicator (AFI). 7Morphological (aneurysm size and aspect ratio) and hemodynamic parameters were compared between ruptured and unruptured aneurysms (see expanded methods in the online only data supplement). Results Univariate AnalysisAs not all morphological and hemodynamic parameters were normally distributed, they were analyzed with the Wilcoxon rank-sum test (Table 1). The median of the size of the aneurysmal dome and the aspect ratio were 5.36 mm and 1.43, respectively, for ruptured aneurysms, and 5.30 mm and 1.33, respectively, for unruptured aneurysms. There was no significant difference in the size of the aneurysmal dome (P=0.122), whereas the aspect ratio was significantly different (P=0.0298).Distributions of WSS, OSI, WSSG, gradient oscillatory number, and AFI for ruptured and unruptured aneurysms are shown in Figure. Ruptured aneurysms had significantly lower WSS, lower NWSS, higher OSI, lower WSSG, and lower AFI than unruptured aneurysms (7.19 Pa versus 9.55 Pa, P=0.00010; 0.490 versus 0.618, P=0.0129; 0.0165 versus 0.0125, P=0.00891; 7.15 Pa/mm versus 10.40 Pa/mm, P=0.00020; and 0.971 versus 0.978, P=0.00631, respectively).Background and Purpose-We determined which hemodynamic parameter independently characterizes the rupture status of middle cerebral artery (MCA) aneurysms using computational fluid dynamics analysis.Methods-In 106 patient-specific geometries of MCA aneurysms (43 ruptured, 63 unruptured), morphological and hemodynamic parameters were compared between the ruptured and unruptured groups. Multivariate logistic regression analysis was performed to determine parameters that independently characterized the rupture status of MCA aneurysms.Results-Univariate analyses showed that the aspect ratio, wall shear stress (WSS), normalized WSS, oscillatory shear index, WSS gradient, and aneurysm-formation index were significant parameters. The size of the aneurysmal dome and the gradient oscillatory number were not significantly different between the 2 groups. With multivariate analyses, only lower WSS was significantly associated with the rupture status of MCA aneurysms. Conclusions-WSS Intercorrelations Among ParametersIntercorrelations between significant parameters with univariate analyses were examined using Multivariate AnalysesBecause WSS had the lowest P value in the Wilcoxon ranksum test among WSS, NWSS, and WSSG, which were significantly correlated, only...

MicroRNAs (miRNAs) are short, noncoding RNAs that function as posttranscriptional regulators of gene expression by controlling translation of mRNAs. A subset of miRNAs may be critical for the control of cell death, including the p53-regulated miRNA, miR-34a. Because seizures activate p53, and p53-deficient mice are reportedly resistant to damage caused by prolonged seizures, we investigated the role of miR-34a in seizure-induced neuronal death in vivo. Status epilepticus was induced by intra-amygdala microinjection of kainic acid in mice. This led to an early (2 h) multifold upregulation of miR-34a in the CA3 and CA1 hippocampal subfields and lower protein levels of mitogen-activated kinase kinase kinase 9, a validated miR-34a target. Immunoprecipitation of the RNA-induced silencing complex component, Argonaute-2, eluted significantly higher levels of miR-34a after seizures. Injection of mice with pifithrin-α, a putative p53 inhibitor, prevented miR-34a upregulation after seizures. Intracerebroventricular injection of antagomirs targeting miR-34a reduced hippocampal miR-34a levels and had a small modulatory effect on apoptosis-associated signaling, but did not prevent hippocampal neuronal death in models of either severe or moderate severity status epilepticus. Thus, prolonged seizures cause subfield-specific, temporally restricted upregulation of miR-34a, which may be p53 dependent, but miR-34a is probably not important for seizure-induced neuronal death in this model.