Ferritin immunoreactivity, and the ferritin heavy chain (FTH) and light chain (FTL) protein levels in cortex at day 3 after sham or subarachnoid hemorrhage induction with deferoxamine (DFX) treatment or vehicle, scale bar = 20μm.

<p>Values are mean ± SD; n = 3 for each group, #p<0.01 vs. SAH+vehicle group at day 3.</p

Effects of deferoxamine on blood-brain barrier disruption after subarachnoid hemorrhage - Fig 3

<p><b>(A</b>) Occludin immunoreactivity and protein levels in cortex after sham or subarachnoid hemorrhage induction with deferoxamine (DFX) treatment or vehicle at day 3, scale bar = 20μm. Values are mean ± SD; n = 3 for each group, #p<0.01, *p<0.05 vs. SAH+vehicle group at day 3. <b>(B)</b> ZO-1 immunoreactivity and protein levels in cortex after sham or subarachnoid hemorrhage induction with deferoxamine (DFX) treatment or vehicle at day 3, scale bar = 20μm. Values are mean ± SD; n = 3 for each group, #p<0.01 vs. SAH+vehicle group at day 3. <b>(C)</b> Claudin-5 immunoreactivity and protein levels in cortex after sham or subarachnoid hemorrhage induction with deferoxamine (DFX) treatment or vehicle at day 3, scale bar = 20μm. Values are mean ± SD; n = 3 for each group, *p<0.05 vs. SAH+vehicle group at day 3.</p

Behavior and activity scores.

<p>Behavior and activity scores.</p

CT perfusion images before and after surgery.

<p>Images show cerebral hemodynamics changes of pre- and post-operation of a left-sided superficial temporal artery-to-middle cerebral artery anastomosis in Moyamoya disease. Axial perfusion CT images show reduced (<b>A</b>) cerebral blood flow (CBF), increased (<b>B</b>) cerebral blood volume (CBV), delayed (<b>C</b>) mean transit time (MTT), and (<b>D</b>) time to peak (TTP) in the region of left middle cerebral artery before surgery. The postoperative whole-brain perfusion CT images show increased (<b>E</b>) CBF, reduced (<b>F</b>) CBV, (<b>G</b>) MTT and (<b>H</b>) TTP in the region of left middle cerebral artery.</p

Comparison of Preoperative Perfusion CT Values of Potential Surgical Side in the Region of Middle Cerebral Artery and Those of Contralateral Side [mean±SD; median (P₂₅–P₇₅)].

<p>CBF = cerebral blood flow, CBV = cerebral blood volume, MTT = mean transit time TTP = time to peak. <i>P</i><0.05 was considered statistically significant. Normal distribution data were expressed as mean±SD while skew distribution of measurement data were expressed as median (P₂₅–P₇₅).* <i>z</i> value was derived by matched-pairs signed-ranks test, and ** <i>t</i> value was derived using paired <i>t</i> test.</p

Comparison of Perfusion CT Values of Surgical Side in the Region of Middle Cerebral Artery Pre- and Post-operation [mean±SD; median (P₂₅–P₇₅)].

<p>CBF = cerebral blood flow, CBV = cerebral blood volume, MTT = mean transit time TTP = time to peak, rCBF = relative cerebral blood flow, rCBV = relative cerebral blood volume, rMTT = relative mean transit time, rTTP = relative time to peak. <i>P</i><0.05 was considered statistically significant. Normal distribution data were expressed as mean±SD while skew distribution of measurement data were expressed as median (P₂₅–P₇₅).</p

Regions of interest (ROIs) were placed on cortical regions in the middle cerebral artery territory.

<p>ROIs were drew in (<b>A</b>) the reference CT image, and (<b>B</b>) vessel-removed mean transit time (MTT) map.</p

CT Angiography (CTA) images in frontal projection before and after bypass in Moyamoya disease.

<p>(<b>A</b>) The preoperative volumetric CTA acquired in the arterial phase of whole-brain CT perfusion (CTP) shows the left internal carotid artery (ICA) is occluded in the supraclinoid portion, and “Moyamoya vessels”(arrow) can be seen in the cerebral base. The right supraclinoid ICA and the proximal anterior cerebral artery (ACA) and middle cerebral artery (MCA) are markedly stenosed. (<b>B</b>) The arrows indicate the left-side direct graft patency with collateral vessels from the left external carotid artery to the MCA territory on the postoperative volumetric CTA acquired in the arterial phase of whole-brain CTP.</p

Molecular Analysis of <em>RNF213</em> Gene for Moyamoya Disease in the Chinese Han Population

<div><h3>Background</h3><p>Moyamoya disease (MMD) is an uncommon cerebrovascular disorder characterized by progressive occlusion of the internal carotid artery causing cerebral ischemia and hemorrhage. Genetic factors in the etiology and pathogenesis of MMD are being increasingly recognized. Previous studies have shown that the <em>RNF213</em> gene was related to MMD susceptibility in the Japanese population. However, there is no large scale study of the association between this gene and MMD in the Chinese Han population. Thus we designed this case-control study to validate the R4810K mutation and to define the further spectrum of <em>RNF213</em> mutations in Han Chinese.</p> <h3>Methodology/Principal Findings</h3><p>Genotyping of the R4810K mutation in the <em>RNF213</em> gene was performed in 170 MMD cases and 507 controls from a Chinese Han population. The R4810K mutation was identified in 22 of 170 MMD cases (13%), including 21 heterozygotes and a single familial homozygote. Two of the 507 controls (0.4%) were heterozygous R4810K carriers. The R4810K mutation greatly increased the risk for MMD (OR = 36.7, 95% CI: 8.6∼156.6, <em>P</em> = 6.1 E-15). The allele frequency of R4810K was significantly different between patients with ischemia and hemorrhage (OR = 5.4, 95% CI: 1.8∼16.1, <em>P</em> = 0.001). Genomic sequencing covering <em>RNF213</em> exon 40 to exon 68 also identified eight other non-R4810K variants; P4007R, Q4367L, A4399T, T4586P, L4631V, E4950D, A5021V and M5136I. Among them A4399T polymorphism was found in 28/170 cases (16.5%) and 45/507 controls (8.9%) and was associated with MMD (OR = 2.0, 95% CI: 1.2∼3.3, <em>P</em> = 0.004), especially with hemorrhage (OR = 2.8, 95% CI: 1.2∼6.5, <em>P</em> = 0.014).</p> <h3>Conclusions</h3><p><em>RNF213</em> mutations are associated with MMD susceptibility in Han Chinese. The ischemic type MMD is particularly related to the R4810K mutation. However, A4399T is also a susceptible variant for MMD, primarily associated with hemorrhage. Identification of novel variants in the <em>RNF213</em> gene further highlights the genetic heterogeneity of MMD.</p> </div

Genetic background of the five familial cases.

<p>(a) Family 1, two brothers both harboring a heterozygous R4810K mutation. (b) Family 2, mother and aunt are whole sisters with A4399T heterozygote and R4810K homozygote respectively. The daughter has both the heterozygous A4399T and R4810K variants. All the patients were diagnosed with the ischemia subtype.</p