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Xin-Yi Gao, Qiao Li, Jing-Run Li, Qian Zhou, Jian-Xun Qu and Zhen-Wei Yao

OBJECTIVE

The authors conducted a study to noninvasively and nonradioactively reveal moyamoya disease (MMD) intracerebral perfusion and perfusion territory supplied by the unilateral internal carotid artery (ICA) and external carotid artery (ECA) and bilateral vertebral arteries (VAs) before surgery and to further identify risk factors for preoperative hemorrhage in adult MMD.

METHODS

Forty-three consecutive adult patients with bilateral MMD underwent unenhanced T1-weighted MRI, territorial arterial spin labeling (t-ASL), and unenhanced 3D time-of-flight MRA (3D-TOF-MRA). Clinical factors, including age, sex, hypertension, diabetes mellitus, hyperlipidemia, current smoking status, and history of taking aspirin, were gathered and stratified. Univariate logistic regression analyses were used to examine the relationship between various risk factors and the occurrence of preoperative hemorrhage. Stepwise multivariate logistic regression analyses were used to determine independent risk factors of preoperative hemorrhage in MMD.

RESULTS

Among the 86 MMD hemispheres, t-ASL revealed 137 perfusion territory shifts in 79 hemispheres. Five distinct categories of perfusion territory shifts were observed on t-ASL maps. The subtypes of perfusion territory shift on t-ASL maps were further subdivided into 2 different categories, group A and group B, in combination with findings on 3D-TOF-MRA. A perfusion territory shift attributable solely to the secondary collaterals was a potential independent risk factor for preoperative hemorrhage (p = 0.026; 95% CI 1.201–18.615; OR 4.729). After eliminating the influence of the secondary collaterals, the primary collaterals had no significant effect on the risk of preoperative hemorrhage (p = 0.182).

CONCLUSIONS

t-ASL could reveal comprehensive MMD cerebral blood perfusion and the vivid perfusion territory shifts fed by the unilateral ICA and ECA and bilateral VAs in a noninvasive, straightforward, nonradioactive, and nonenhanced manner. 3D-TOF-MRA could subdivide t-ASL perfusion territory shifts according to their shunt arteries. A perfusion territory shift attributable to the secondary collaterals is a potential independent risk factor for preoperative hemorrhage in MMD patients. A perfusion territory shift fed by the primary collaterals may not have a strong effect on preoperative hemorrhage in MMD patients. These findings make the combined modalities of t-ASL and 3D-TOF-MRA a feasible tool for MMD disease assessment, management, and surgical strategy planning.

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Xin-Yi Gao, Qiao Li, Jing-Run Li, Qian Zhou, Jian-Xun Qu and Zhen-Wei Yao

OBJECTIVE

The authors conducted a study to noninvasively and nonradioactively reveal moyamoya disease (MMD) intracerebral perfusion and perfusion territory supplied by the unilateral internal carotid artery (ICA) and external carotid artery (ECA) and bilateral vertebral arteries (VAs) before surgery and to further identify risk factors for preoperative hemorrhage in adult MMD.

METHODS

Forty-three consecutive adult patients with bilateral MMD underwent unenhanced T1-weighted MRI, territorial arterial spin labeling (t-ASL), and unenhanced 3D time-of-flight MRA (3D-TOF-MRA). Clinical factors, including age, sex, hypertension, diabetes mellitus, hyperlipidemia, current smoking status, and history of taking aspirin, were gathered and stratified. Univariate logistic regression analyses were used to examine the relationship between various risk factors and the occurrence of preoperative hemorrhage. Stepwise multivariate logistic regression analyses were used to determine independent risk factors of preoperative hemorrhage in MMD.

RESULTS

Among the 86 MMD hemispheres, t-ASL revealed 137 perfusion territory shifts in 79 hemispheres. Five distinct categories of perfusion territory shifts were observed on t-ASL maps. The subtypes of perfusion territory shift on t-ASL maps were further subdivided into 2 different categories, group A and group B, in combination with findings on 3D-TOF-MRA. A perfusion territory shift attributable solely to the secondary collaterals was a potential independent risk factor for preoperative hemorrhage (p = 0.026; 95% CI 1.201–18.615; OR 4.729). After eliminating the influence of the secondary collaterals, the primary collaterals had no significant effect on the risk of preoperative hemorrhage (p = 0.182).

CONCLUSIONS

t-ASL could reveal comprehensive MMD cerebral blood perfusion and the vivid perfusion territory shifts fed by the unilateral ICA and ECA and bilateral VAs in a noninvasive, straightforward, nonradioactive, and nonenhanced manner. 3D-TOF-MRA could subdivide t-ASL perfusion territory shifts according to their shunt arteries. A perfusion territory shift attributable to the secondary collaterals is a potential independent risk factor for preoperative hemorrhage in MMD patients. A perfusion territory shift fed by the primary collaterals may not have a strong effect on preoperative hemorrhage in MMD patients. These findings make the combined modalities of t-ASL and 3D-TOF-MRA a feasible tool for MMD disease assessment, management, and surgical strategy planning.

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Guang Yang, Zhendong Liu, Lu Wang, Xin Chen, Xiaoxiong Wang, Qi Dong, Daming Zhang, Zhao Yang, Qi Zhou, Jingxian Sun, Linmeng Xue, Xinzhuang Wang, Ming Gao, Lili Li, Ran Yi, Gareev Ilgiz, Jing Ai and Shiguang Zhao

OBJECTIVE

It has been reported that microRNA-195 (miR-195) protects against chronic brain injury induced by chronic brain hypoperfusion. However, neither the expression profile of miR-195 nor its potential role during acute ischemic stroke has been investigated. In this study, the authors’ aim was to verify the mechanism of miR-195 in acute ischemic stroke.

METHODS

The plasma levels of miR-195 expression were assessed using real-time PCR in 96 patients with acute ischemic stroke, and the correlation with the National Institutes of Health Stroke Scale score was evaluated. In addition, cerebral infarct volume, neurological score, and levels of miR-195 and CX3CL1/CX3CR1 mRNA and protein expression were assessed in mice subjected to middle cerebral artery occlusion (MCAO) with or without intra-cerebroventricular infusion of lentiviral vector. The inflammatory cytokines tumor necrosis factor–α (TNFα), interleukin (IL)–1β, and IL-6 of mouse brains after MCAO and BV2 cells treated with oxygen-glucose deprivation were measured using enzyme-linked immunosorbent assay, and apoptotic proteins were examined by Western blotting. Direct targeting of CX3CL1/CX3CR1 by miR-195 was determined by immunoblotting and dual luciferase assay.

RESULTS

In ischemic stroke patients, miR-195 was significantly downregulated and expression levels of miR-195 in these patients negatively correlated with the National Institutes of Health Stroke Scale score. In mice after MCAO, miR-195 overexpression decreased infarct volume, alleviated neurological deficits, and most importantly, suppressed an inflammatory response. Meanwhile, miR-195 suppressed the expression of the inflammatory cytokines TNFα, IL-1β, and IL-6 in vitro and in vivo. The authors further discovered that both CX3CL1 and CX3CR1 are direct targets of miR-195, but miR-195 exerts neuroprotective roles mainly through inhibiting CX3CR1-mediated neuroinflammation and subsequent neuronal cell apoptosis.

CONCLUSIONS

Taken together, these findings suggest that miR-195 promotes neuronal cell survival against chronic cerebral ischemic damage by inhibiting CX3CR1-mediated neuroinflammation. This indicates that miR-195 may represent a novel target that regulates neuroinflammation and brain injury, thus offering a new treatment strategy for cerebral ischemic disorders.

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Dong Wang, Chuang Gao, Xin Xu, Tao Chen, Ye Tian, Huijie Wei, Shu Zhang, Wei Quan, Yi Wang, Shuyuan Yue, Zengguang Wang, Ping Lei, Craig Anderson, Jingfei Dong, Jianning Zhang and Rongcai Jiang

OBJECTIVE

The authors sought to test the hypothesis that adding dexamethasone (DXM) to atorvastatin (ATO) potentiates the effects of ATO on chronic subdural hematoma (CSDH).

METHODS

Sixty patients with CSDH underwent 5 weeks of treatment with an additional 7-week follow-up. Patients were randomized to receive a 5-week regimen of ATO 20 mg daily or ATO 20 mg daily plus a DXM regimen (ATO+DXM). The 5-week DXM regimen was 2.25 mg daily for 2 consecutive weeks, followed by 0.75 mg twice daily for 2 weeks and 0.75 mg once daily for 1 week. The primary endpoint was hematoma reduction assessed by neuroimaging at baseline and at 5 weeks of follow-up. Secondary outcomes included neurological improvement assessed by using the Markwalder’s Grading Scale and Glasgow Coma Scale (MGS-GCS).

RESULTS

The mean patient age was 66.6 years, and 25% of patients were women. The patients who were treated with ATO+DXM had more obvious hematoma reduction at the 5th week (between-groups difference 18.37 ml; 95% CI 8.17–28.57; p = 0.0005). This reduction started from the 2nd week (14.51 ml; 95% CI 4.31–24.71; p = 0.0056) of treatment and persisted until the 12th week (17.50 ml; 95% CI 7.30–27.70; p = 0.0009). Complete recovery of neurological function (MGS-GCS grade 0) at 5 weeks was achieved in 83.33% and 32.14% of patients in the ATO+DXM and ATO groups, respectively. At the 5th week, patients receiving ATO+DXM had significantly lower levels of T cells and higher levels of regulatory T cells and endothelial progenitor cells in their peripheral blood.

CONCLUSIONS

ATO+DXM was more effective than ATO alone in reducing hematoma and improving neurological function in patients with CSDH. These results require further confirmation in a randomized placebo-controlled trial.

Clinical trial registration no.: ChiCTR-IPR-14005573 (http://www.chictr.org.cn/index.aspx)