Serum phosphorus concentration and its association with the degree and pattern of intracranial arterial calcification.

BACKGROUND AND AIM: The aim of this study was to determine whether the serum phosphorus concentrations (SPC) are associated with the degree and pattern of intracranial arterial calcification (IAC) in patients with normal renal function or mild-moderate renal impairment. METHODS AND RESULTS: A total of 513 patients were enrolled in this study. The degree of IAC measured by IAC scores was evaluated on non-contrast head computed tomography (CT) images and IAC was classified as intimal or medial calcification. Study participants were classified according to IAC degrees (mild, moderate and severe) and patterns (intimal and medial calcification). A multivariate regression model was used to assess the independent relationship of SPC with IAC scores and patterns. Of 513 study participants (mean [SD] age, 68.3 [10.3] years; 246 females [48%]), the mean SPC was 1.07 ± 0.17 mmol/L and IAC scores was 4.0 (3.0-5.0). Multivariate analysis showed that higher serum phosphorus was a significant risk factor for moderate/severe IAC in both patients with eGFR ≥60 ml/min/1.73 m2 (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.01-1.59; P < 0.05) and eGFR <60 ml/min/1.73 m2 (OR, 1.92; 95% CI, 1.04-3.57; P < 0.05), when those with mild IAC were considered as the reference group. However, higher SPC was associated with an increased odds of medial calcification only in patients with eGFR <60 ml/min/1.73 m2 (OR, 1.67; 95% CI, 1.08 to 2.61). CONCLUSIONS: High levels of serum phosphorus were positively correlated with the degree of IAC, and this significant effect on medial IAC was only present in patients with impaired renal function (eGFR <60 ml/min/1.73 m2).

Sympathetic skin response for early detection of type 2 diabetic peripheral neuropathy and nephropathy.

BACKGROUND: Diabetic peripheral neuropathy (DPN) and diabetic nephropathy (DN) are common complications of type 2 diabetes mellitus (T2DM). Although nerve conduction studies (NCS) and sympathetic skin response (SSR) can detect DPN, the more sensitive method for early diagnosis remains unclear. Furthermore, whether DPN can be used as a predictor for diabetic nephropathy needs clarification. METHODS: We evaluated nerve conduction studies, sympathetic skin response, and the diabetic nephropathy indicator microalbuminuria (MAU) in 192 patients with type 2 diabetes mellitus and 50 healthy controls. RESULTS: Patients with type 2 diabetes mellitus showed a lower sensory nerve conduction velocity (SCV), sensory active nerve potential (SNAP), motor nerve conduction velocity (MCV), and compound motor action potential (CMAP) than the controls on NCS. Abnormal rates for nerve conduction studies and sympathetic skin response were 75.0% and 83.3%, respectively, in patients with type 2 diabetes mellitus. Interestingly, 54.2% of patients with normal nerve conduction studies had an abnormal sympathetic skin response. Moreover, we found a positive correlation between sympathetic skin response and microalbuminuria for the first time. The abnormal rate of microalbuminuria was 53.8%, lower than that of abnormal nerve conduction studies or sympathetic skin response patients. CONCLUSION: Sympathetic skin response is a more sensitive method than nerve conduction studies for the early diagnosis of diabetic peripheral neuropathy. Abnormal sympathetic skin response might serve as an indicator for early diabetic nephropathy. Additionally, diabetic peripheral neuropathy may occur earlier than diabetic nephropathy in the development of type 2 diabetes mellitus.

Higher critical closing pressure is independently associated with enlarged basal ganglia perivascular spaces.

Objective: This study aimed to explore the association between cerebral hemodynamic parameters focused on the critical closing pressure (CCP) and enlarged perivascular spaces (EPVS). Methods: Cerebral blood velocity in the middle cerebral artery (MCAv) and non-invasive continuous blood pressure (NIBP) were measured using a transcranial Doppler (TCD) and Finometer, followed by the calculation of cerebral hemodynamic parameters including CCP, resistance area product (RAP), pulsatility index (PI), and pulse pressure (PP). EPVS were graded separately in the basal ganglia (BG) and centrum semiovale (CSO), using a visual semiquantitative ordinal scale. Patients with EPVS >10 were classified into the severe BG-EPVS group and severe CSO-EPVS group, and the remainder into the mild BG-EPVS group and the mild CSO-EPVS group. Spearman's correlation and binary logistic regression analysis were performed to analyze the relationship between hemodynamic parameters and BG-EPVS and CSO-EPVS, respectively. Results: Overall, 107 patients were enrolled. The severe BG-EPVS group had higher CCP, mean arterial blood pressure (MABP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) than that in the mild BG-EPVS group (p < 0.05). There was no statistical difference in hemodynamic parameters between the severe CSO-EPVS group and the mild CSO-EPVS group. Spearman's correlation analysis showed that CCP was positively associated with BG-EPVS (rho = 0.331, p < 0.001) and CSO-EPVS (rho = 0.154, p = 0.044). The binary logistic regression analysis showed that CCP was independently associated with severe BG-EPVS (p < 0.05) and not with CSO-EPVS (p > 0.05) after adjusting for confounders. Conclusion: CCP representing cerebrovascular tension was independently associated with BG-EPVS.

Brachial-ankle pulse wave velocity is associated with intracranial artery calcification in acute stroke patients.

BACKGROUND: Intracranial artery calcification (IAC) is closely associated with cerebrovascular disease. Brachial-ankle pulse wave velocity (baPWV) is a noninvasive method for estimating arterial stiffness, which reflects the stiffness of peripheral arteries. This study aimed to examine the association of baPWV with the presence and degree of IAC in patients with acute ischemic stroke. METHODS: A total of 143 ischemic stroke subjects were recruited. A head computed tomography (CT) scan was used to assess the presence and severity of IAC. The oscillometric method was used to simultaneously measure bilateral brachial and posterior tibial arterial pulse waveforms and arterial BP. Multiple logistic regression analysis was used to identify the independent relationship between baPWV and IAC. RESULTS: 143 subjects were included in this study. The demographic and clinical characteristics of the study population were classified according to the baPWV quartile. A higher prevalence of IAC was noted across increasing baPWV quartiles (Q1: 53 %, Q2: 69 %, Q3: 86 %, Q4: 94 %, P < 0.001). IAC scores were also increased with elevated ccPWV values (1.60 ± 1.71; 2.56 ± 1.99; 3.44 ± 1.91; 4.64 ± 1.58. P < 0.001). After an additional adjustment for age and hypertension, the odds ratio (95 % confidence interval) for the IAC scores was 1.61 (1.06-2.45; P = 0.025) in the top quartile of baPWV compared with those in the lowest quartile. CONCLUSIONS: Arterial stiffness as defined by baPWV was positively associated with the degree of IAC in patients with acute ischemic stroke, suggesting the severity of IAC may also be a marker of peripheral or systemic arterial stiffness.

Critical closing pressure as a new hemodynamic marker of cerebral small vessel diseases burden.

Purpose: To investigate cerebrovascular hemodynamics, including critical closing pressure (CrCP) and pulsatility index (PI), and their independent relationship with cerebral small vessel disease (CSVD) burden in patients with small-vessel occlusion (SVO). Methods: We recruited consecutive patients with SVO of acute cerebral infarction who underwent brain magnetic resonance imaging (MRI), transcranial Doppler (TCD) and CrCP during admission. Cerebrovascular hemodynamics were assessed using TCD. We used the CSVD score to rate the total MRI burden of CSVD. Multiple regression analysis was used to determine parameters related to CSVD burden or CrCP. Results: Ninety-seven of 120 patients (mean age, 64.51 ± 9.99 years; 76% male) completed the full evaluations in this study. We observed that CrCP was an independent determinant of CSVD burden in four models [odds ratio, 1.41; 95% confidence interval (CI), 1.17-1.71; P < 0.001] and correlated with CSVD burden [ß (95% CI): 0.05 (0.04-0.06); P < 0.001]. In ROC analysis, CrCP was considered as a predictor of CSVD burden, and AUC was 86.2% (95% CI, 78.6-93.9%; P < 0.001). Multiple linear regression analysis showed that CrCP was significantly correlated with age [ß (95% CI): 0.27 (0.06 to 0.47); P = 0.012], BMI [ß (95% CI): 0.61 (0.00-1.22)] and systolic BP [ß (95% CI): 0.16 (0.09-0.23); P < 0.001]. Conclusions: CrCP representing cerebrovascular tension is an independent determinant and predictor of CSVD burden. It was significantly correlated with age, BMI and systolic blood pressure. These results provide new insights in the mechanism of CSVD development.

Cerebral Arterial Stiffness as Measured Based on the Pulse Wave Velocity is Associated With Intracranial Artery Calcification in Patients With Acute Stroke.

BACKGROUND AND PURPOSE: By measuring a newly defined parameter, the carotid-cerebral pulse wave velocity (ccPWV), this study aimed to determine the association of intracranial artery calcification (IAC) with arterial stiffness as reflected by the pulse wave velocity between the carotid and middle cerebral arteries using transcranial Doppler sonography in patients with acute stroke. METHODS: We recruited 146 patients with ischemic stroke from our stroke center. Computed tomography of the head was used to assess the presence and severity of IAC. Arterial stiffness was evaluated using ccPWV. Data are presented as quartiles of ccPWV. A multivariable logistic regression model was used to assess the independent relationship between ccPWV and IAC. RESULTS: The IAC prevalence increased with the ccPWV quartile, being 54%, 76%, 83%, and 89% for quartiles 1, 2, 3, and 4, respectively (p<0.001) as did IAC scores, with median [interquartile range] values of 0 [0-2], 3 [2-4], 4 [2-5], and 5 [4-6], respectively (p<0.001). After additionally adjusting for age and hypertension, a significant correlation was only found between quartiles 3 and 4 of ccPWV and IAC scores. The odds ratio (95% confidence interval) for the IAC scores was 1.78 (1.28-2.50) (p=0.001) in quartile 4 of ccPWV and 1.45 (1.07-1.95) (p=0.015) in quartile 3 compared with quartile 1. CONCLUSIONS: We found that in patients with acute ischemic stroke, ccPWV was positively related to the degree of IAC. Future longitudinal cohort studies may help to identify the potential role of IAC in the progression of cerebral arterial stiffness.

Estimation of critical closing pressure using intravascular blood pressure of the common carotid artery.

PURPOSE: Radial artery, femoral artery, and aortic arterial blood pressures (ABPs) can be used to estimate cerebral critical closing pressure (CrCP) and resistance-area product (RAP). However, the use of the common carotid artery (CCA) intravascular blood pressure to estimate CrCP is unclear. Thus, using continuous ABP monitoring, we compared the CrCP and RAP estimated from CCA measurements with the corresponding values acquired from the radial artery. METHODS: In this retrospective cross-sectional study, we analyzed CrCP and RAP estimations from 21 patients with normal cerebral blood vessels between July 23, 2010, and February 9, 2011, using linear regression of the cerebral blood flow velocity-ABP relationship. RESULTS: Bland-Altman analysis showed that the average differences (95% limits of agreement) between the radial artery and the left CCA were -6.3 (-53.1 - 40.6) mmHg and -0.08 (-0.41 - 0.25) mmHg s cm-1 for CrCP and RAP, respectively. CONCLUSIONS: The CrCP and RAP estimated from the CCA measurements are consistent with the corresponding values obtained from the radial artery.

Current Status of Endovascular Treatment for Acute Large Vessel Occlusion in China: A Real-World Nationwide Registry.

BACKGROUND AND PURPOSE: The benefit of endovascular treatment (EVT) for large vessel occlusion in clinical practice in developing countries like China needs to be confirmed. The aim of the study was to determine whether the benefit of EVT for acute ischemic stroke in randomized trials could be generalized to clinical practice in Chinese population. METHODS: We conducted a prospective registry of EVT at 111 centers in China. Patients with acute ischemic stroke caused by imaging-confirmed intracranial large vessel occlusion and receiving EVT were included. The primary outcome was functional independence at 90 days defined as a modified Rankin Scale score of 0 to 2. Outcomes of specific subgroups in the anterior circulation were reported and logistic regression was performed to predict the primary outcome. RESULTS: Among the 1793 enrolled patients, 1396 (77.9%) had anterior circulation large vessel occlusion (median age, 66 [56-73] years) and 397 (22.1%) had posterior circulation large vessel occlusion (median age, 64 [55-72] years). Functional independence at 90 days was reached in 45% and 44% in anterior and posterior circulation groups, respectively. For anterior circulation population, underlying intracranial atherosclerotic disease was identified in 29% of patients, with higher functional independence at 90 days (52% versus 44%; P=0.0122) than patients without intracranial atherosclerotic disease. In the anterior circulation population, after adjusting for baseline characteristics, procedure details, and early outcomes, the independent predictors for functional independence at 90 days were age <66 years (odds ratio [OR], 1.733 [95% CI, 1.213-2.476]), time from onset to puncture >6 hours (OR, 1.536 [95% CI, 1.065-2.216]), local anesthesia (OR, 2.194 [95% CI, 1.325-3.633]), final modified Thrombolysis in Cerebral Infarction 2b/3 (OR, 2.052 [95% CI, 1.085-3.878]), puncture-to-reperfusion time ≤1.5 hours (OR, 1.628 [95% CI, 1.098-2.413]), and National Institutes of Health Stroke Scale score 24 hours after the procedure <11 (OR, 9.126 [95% CI, 6.222-13.385]). CONCLUSIONS: Despite distinct characteristics in the Chinese population, favorable outcome of EVT can be achieved in clinical practice in China. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03370939.

Hyperhomocysteinemia Independently Associated with Adult Moyamoya Disease: Hospital Based Study of 237 Patients.

AIM: To clarify the risk factors for adult moyamoya disease (MMD) in patients from South China. MATERIAL AND METHODS: We prospectively studied adult patients who were diagnosed angiographically with MMD. The demographic profiles, medical history and clinical characteristics were compared between adult MMD and non-MMD stroke patients. Logistic regression analysis was used to determine the risk factors associated with adult MMD. RESULTS: A total of 35 adult MMD patients and 202 adults patients with non-MMD stroke were included. Of the 35 MMD patients, bilateral MMD occurred in 48.6% and bypass surgery was performed in 28.6%; these figures were significantly lower than those reported in patients from Korea and the United States (p < 0.05). After adjusting for baseline demographics and potential confounders, multivariate logistic regression analysis was conducted, which showed that the plasma homocysteine level (odds ratio [OR]: 1.10; 95% confidence interval [CI]: 1.06?1.14) and occupation as a technological worker (OR: 4.23; 95% CI: 1.65?10.89) were independently associated with adult MMD. CONCLUSION: Hyperhomocysteinemia and type of occupation were found to be independent risk factors for adult MMD in patients from South China. However, there is still a need for further research to clarify the pathogenesis of MMD. Given the lack of understanding about the risk factors and prevention measures for MMD, we suggest bypass surgery be used for MMD treatment in clinical practice in China to achieve more desirable effects in the management of the disease.

L-3-n-Butylphthalide Effectively Improves the Glymphatic Clearance and Reduce Amyloid-ß Deposition in Alzheimer's Transgenic Mice.

Amyloid-ß (Aß) deposit in the parenchyma is a major characteristic in Alzheimer's disease (AD), and the impaired glymphatic clearance contributes to the Aß accumulation. It was reported that L-3-n-butylphthalide (NBP) showed the potential neuroprotective effect in the rodent models of AD. The effects of NBP on the glymphatic system were explored in this study. In the wild-type mice, both CSF tracer influx and perivascular drainage increased after NBP treatment compared with vehicle treatment. Moreover, NBP promoted the perivascular drainage of Aß via increased cerebral pulsation, which could be inhibited by propranolol. Then, we studied the potential of 3-month NBP treatment on Aß deposits in 8-month-old APP/PS1 transgenic mice. NBP daily treatments remarkably improved cognitive behavior in Morris water maze. Furthermore, NBP could reduce Aß deposition and decrease parenchymal Aß levels. In addition, NBP markedly improved the perivascular AQP4 localization. Our results indicated that NBP could enhance the glymphatic clearance and reduce parenchymal Aß deposit in the APP/PS1 mice, suggesting that it may have potential in the treatment of AD.

Cerebral arterial stiffness for predicting functional outcome in acute ischemic stroke.

To assess the association between cerebral arterial stiffness measured using the carotid-cerebral pulse wave velocity (ccPWV) and the functional outcome after acute ischemic stroke (AIS). We prospectively studied 336 consecutive patients (mean age, 60.58 ± 9.89 years; 73.81% male) with first-ever AIS who underwent examination by multimodal brain magnetic resonance, ccPWV, echocardiography, and carotid ultrasonography during the admission period. Ischemic stroke subtypes were classified using the Trial of Org 10172 in Acute Stroke Treatment classification system. A poor functional outcome was defined as a modified Rankin Scale score >2 at 3 months after stroke onset. We observed that 110 (32.74%) patients had a poor functional outcome. Multivariate logistic regression analysis revealed that ccPWV ≥ 6.66 m/s, calculated from the receiver operating characteristic (ROC) curve, was an independent predictor of a poor functional outcome [adjusted odds ratio, 6.27; 95% confidence interval (CI), 2.07-18.99]. ROC curve analysis showed that the area under the curve of ccPWV for predicting the 3-month functional outcome after AIS was 85.27% (95% CI, 80.95-89.58; P < 0.001). The optimal ccPWV cutoff point was 6.66 m/s, with a sensitivity of 82.73% and specificity of 77.88%. Furthermore, the addition of ccPWV to the predictive model significantly improved the discrimination ability for a poor functional outcome. Cerebral arterial stiffness, measured using the ccPWV on admission, has value as an independent prognostic factor for predicting the long-term functional outcome in patients with AIS.

Association Between Carotid-Cerebral Pulse Wave Velocity and Acute Ischemic Stroke: Clinical Trial Protocol.

BACKGROUND: Pulse wave velocity is commonly regarded as the most effective and noninvasive indicator for evaluating arterial stiffness, while increased arterial stiffness is known to be related to atherosclerosis, which has been proved to play a significant role on the onset of acute ischemic stroke. However, it is still only used in the assessment of central and peripheral arteries. Our previous studies have found that carotid-cerebral pulse wave velocity measured using transcranial Doppler may be a promising method for the assessment of human cerebral arterial stiffness. This trial was designed to examine the association between carotid-cerebral pulse wave velocity and acute ischemic stroke. METHODS: In a single-center, single-arm, prospective clinical trial, patients with acute ischemic stroke who had anterior circulation infarcts confirmed by magnetic resonance imaging are eligible to receive measurement of carotid-cerebral pulse wave velocity, which is measured in the supine position with transcranial Doppler that using 2-MHz and 4-MHz ultrasound probes by 2 experienced operators. Subjects will be received follow-up for 1 year. Vascular and nonvascular death at follow-up will be assessed as primary outcomes. Secondary outcomes include intracerebral hemorrhage, subarachnoid hemorrhage, transient ischemic attack, recurrence or aggravation of ischemic stroke. CONCLUSION: This trial will be the first to evaluate carotid-cerebral pulse wave velocity in patients with acute ischemic stroke using transcranial Doppler. The results may provide more valuable theoretical basis for the prevention, treatment, and prognosis of acute ischemic stroke.

miR-15b-5p targeting amyloid precursor protein is involved in the anti-amyloid eflect of curcumin in swAPP695-HEK293 cells.

Curcumin exerts a neuroprotective effect on Alzheimer's disease; however, it is not known whether microRNAs are involved in this protective effect. This study was conducted using swAPP695-HEK293 cells as an Alzheimer's disease cell model. swAPP695-HEK293 cells were treated with 0, 0.5, 1, 2, 5, and 10 µM curcumin for 24 hours. The changes in miR-15b-5p, miR-19a-3p, miR-195-5p, miR-101-3p, miR-216b-5p, miR-16-5p and miR-185-5p expression were assessed by real-time quantitative polymerase chain reaction. The mRNA and protein levels of amyloid precursor protein, amyloid-ß40 and amyloid-ß42 were evaluated by quantitative real-time polymerase chain reaction, western blot assays and enzyme-linked immunosorbent assays. swAPP695-HEK293 cells were transfected with miR-15b-5p mimic, or treated with 1 µM curcumin 24 hours before miR-15b-5p inhibitor transfection. The effects of curcumin on amyloid precursor protein, amyloid-ß40 and amyloid-ß42 levels were evaluated by western blot assays and enzyme-linked immunosorbent assay. Luciferase assays were used to analyze the interaction between miR-15b-5p and the 3'-untranslated region of amyloid precursor protein. The results show that amyloid precursor protein and amyloid-ß expression were enhanced in swAPP695-HEK293 cells compared with HEK293 parental cells. Curcumin suppressed the expression of amyloid precursor protein and amyloid-ß and up-regulated the expression of miR-15b-5p in swAPP695-HEK293 cells. In addition, we found a negative association of miR-15b-5p expression with amyloid precursor protein and amyloid-ß levels in the curcumin-treated cells. Luciferase assays revealed that miR-15b-5p impaired the luciferase activity of the plasmid harboring the 3'-untranslated region of amyloid precursor protein. These findings indicate that curcumin down-regulates the expression of amyloid precursor protein and amyloid-ß in swAPP695-HEK293 cells, which was partially mediated by miR-15b-5p via targeting of the 3'-untranslated region of amyloid precursor protein.

Association of Cerebral Arterial Stiffness with Initial Severity in Acute Ischemic Stroke.

AIM: To evaluate the association between cerebral arterial stiffness, measured using carotid-cerebral pulse wave velocity (ccPWV), and the initial severity estimated by the National Institutes of Health Stroke Scale (NIHSS) after acute ischemic stroke (AIS). METHODS: We prospectively studied 402 consecutive patients with first-ever acute cerebral infarction who underwent brain multimodal magnetic resonance, ccPWV, echocardiography, and carotid ultrasonography during the admission period. Their stroke subtypes were classified using the Trial of Org 10172 in Acute Stroke Treatment classification. Severe initial stroke severity was defined as an NIHSS score ＞6 on admission. RESULTS: We observed that 168 (41.79%) patients had severe initial stroke severity. A multivariate logistic regression analysis revealed that ccPWV [as a continuous variable; odds ratios (OR) (95% confidence intervals (CI)): 1.36 (1.08-1.72); P=0.010] and ccPWV ＞6.87 m/s [OR (95% CI): 8.13 (3.06-21.58); P＜0.001], calculated from the receiver-operating characteristic curve, remained independent determinants of severe initial stroke severity in three models. Furthermore, we observed that ccPWV significantly correlated with the NIHSS score, and the value of ccPWV was most strongly correlated with the NIHSS score (r=0.82, P＜0.001) in subjects with small vessel occlusion (SVO) among all stroke subtypes. CONCLUSIONS: Cerebral arterial stiffness was independently associated with initial severity in AIS patients, and may be more strongly correlated with the initial SVO severity than those of other subtypes.

Cerebral Arterial Stiffness as A New Marker of Early Stage Atherosclerosis of The Cerebral Large Artery in Acute Stroke.

AIM: Carotid-cerebral pulse wave velocity (ccPWV) reflects the segment (C-M segment) stiffness between the common carotid artery and ipsilateral middle cerebral artery. C-M segment atherosclerosis (CMSA) is regarded the most frequent cause of anterior circulation ischemic stroke. We aimed to evaluate the association of ccPWV with early stage CMSA in this study. METHODS: Eighty-one acute ischemic stroke (AIS) patients with 154 C-M segments who were successfully evaluated with digital subtraction angiography, ccPWV, carotid intima-media thickness (cIMT), and brachial-ankle pulse wave velocity were enrolled into this study. Patient demographics and clinical data were retrieved from our AIS databases. RESULTS: Multivariate analyses showed that CMSA was independently associated with higher systolic BP, ccPWV, and cIMT. ccPWV and cIMT presented good diagnostic values for evaluating early stage CMSA in the receiver operating characteristic curve analyses. The areas under the curve (AUCs) of ccPWV were significantly higher than that of cIMT (Z=2.204, P=0.007). The AUC, sensitivity, specificity, Youden index, and cutoff of ccPWV for detecting early stage CMSA were 0.815 (P＜0.001), 86%, 70.7%, 0.567, and 5.4 m/s, respectively. Furthermore, ccPWV was significantly correlated with the stenosis of CMSA at the early stage in Spearman's correlation analyses (r=0.877, P＜0.001) and fractional polynomial plot with 95% confidence intervals. CONCLUSIONS: Cerebral arterial stiffness has the potential to be a new marker of early stage atherosclerosis of the cerebral large artery. This finding may help us prevent the occurrence of stroke and decrease the burden of society from stroke patients.

Liberating carotid arteries: measuring arterial pressure through femoral artery in mice.

Researches involving arterial pressure measurements in mice have primarily relied on carotid arterial catheterization. However, in some circumstances, measuring arterial pressure through the carotid arterial impairs accuracy. This study was aimed to evaluate whether femoral artery could displace carotid artery for the blood pressure (BP) measurements in mice. Fifty-six Swiss mice (n = 14 in each group) were randomized into four groups: control, left femoral artery, right femoral artery, and union group, in which BP was measured through left carotid, left femoral, right femoral artery, and simultaneously from right femoral artery and left carotid artery, respectively. Arterial pressure was recorded for 5 min after catheterization. There was no significant difference of the success rate and mortality rate among four groups (P > 0.05), and no obvious difference (P > 0.05) of catheterization time among the first three groups. For intergroup comparison of arterial pressure, there was no significant difference (P > 0.05) of the systolic blood pressure (SBP), diastolic BP, mean arterial pressure, and pulse pressure among the first three groups. For intragroup comparison, SBP, diastolic blood pressure (DBP), mean arterial pressure (MAP) monitored from right femoral artery were similar (P > 0.05) with those from left carotid artery, with significantly positive correlation. The mean values of difference of SBP, DBP, and MAP were -1.3, 1.2, and 0.5 mmHg, respectively. Our results indicated that femoral artery catheterization could be a safe, feasible, reliable, and accuracy alternative for the direct measurement of arterial pressure in anesthesia mice.

Association between Cerebral Arterial Stiffness and Large Artery Atherosclerosis in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Carotid-cerebral pulse wave velocity (ccPWV) reflects the segment (C-M segment) stiffness between common carotid artery and ipsilateral middle cerebral artery. The C-M segment atherosclerosis (CMSA) is regarded as a most frequent cause of anterior circulation ischemic stroke. We therefore, attempted to investigate the relationship between cerebral arterial stiffness and CMSA, and provide reliable data for the early diagnosis of CMSA. METHODS: Between June 2012 and August 2016, 81 acute ischemic stroke (AIS) patients with 154 C-M segments successfully evaluated with digital subtraction angiography and ccPWV were enrolled into this study. Patient demographics and clinical data were retrieved from our AIS databases. RESULTS: Multivariate analyses showed that ccPWV was independently associated with CMSA (ß = 39.6, P = .009) and Systolic blood pressure (ß = 7.1, P < .001) in AIS patients. The values of ccPWV had a trend to be higher in the groups with more lesions (F = 45.9, P < .01) and severer stenosis (F = 102.6, P = .000), and was positively correlated with the number of lesions (r = .662, P = .000), and degree of stenosis (r = .858, P = .000) of CMSA. The fractional polynomial plots with 95% CIs also describe the close relationship between ccPWV and the number of lesions and degree of stenosis in CMSA. CONCLUSIONS: Cerebral arterial stiffness is independently associated with the presence of CMSA, closely related to the vascular damage of C-M segment and reflects the vascular structure change of C-M segment in AIS patients. It may have the potential for assessment of CMSA in its initial stage.

Vascular endothelial growth factor aggravates cerebral ischemia and reperfusion-induced blood-brain-barrier disruption through regulating LOC102640519/HOXC13/ZO-1 signaling.

BACKGROUND/OBJECTIVE: Vascular endothelial growth factor (VEGF) has been recognized to be a potential pharmaceutical target for treating ischemic stroke, but its severe side effects hinder its widely application. Here, the present study was designed to investigate the effects of VEGF on blood-brain-barrier (BBB) disruption and the underlying mechanisms. METHODS: A mouse model of middle cerebral artery occlusion (MCAO) was constructed and treated with or without VEGF. Meanwhile, mice brain microvascular endothelial cells in co-culture with astrocytes were subjected to 1, 2 and 4 h oxygen-glucose deprivation followed by 24 h of reperfusion (OGD/R) in the absence or presence of VEGF. The mRNA and protein expression were assessed by real-time PCR and Western blotting. Fluorescence in situ hybridization (FISH) was utilized to validate LOC102640519 expression in OGD/R cell models. Chromatin Immunoprecipitation (ChIP) assay was used to confirm the regulatory mechanism of LOC102640519 to HOXC13. Interactions between HOXC13 and ZO-1 were measured by a luciferase reporter assay and RNA pull down assay. RESULTS: Our results showed that administration of VEGF significantly aggravated BBB by upregulating LOC102640519 and HOXC13 expression in vitro and vitro model of cerebral ischemia. Furthermore, LOC102640519 positively regulated the expression of HOXC13, thus negatively regulated the expression of ZO-1, Occludin and Claudin-5 in OGD/R model in the absence or presence of VEGF. CONCLUSIONS: VEGF aggravated BBB disruption after cerebral I/R-induced injury probably by increasing LOC102640519 and HOXC13 through inhibition of ZO-1, Occludin and Claudin-5.

Is Metabolic Syndrome Associated with the Risk of Recurrent Stroke: A Meta-Analysis of Cohort Studies.

BACKGROUND: The association between metabolic syndrome (MetS) and recurrence of stroke remains unknown. We summarized the evidence by a meta-analysis of prospective cohort studies. METHODS: We searched the PubMed, EMBASE, and Google Scholar databases from their inception until July 2016 for cohort studies investigating this research question; relevant information was extracted by 2 independent investigators, and then aggregated using the random-effects meta-analysis approach. RESULTS: We identified 5 studies, including 7752 stroke patients who had a history of stroke or transient ischemic attack. Compared with persons without MetS, persons with MetS have a significantly higher risk of recurrent stroke, and the pooled relative risk (RR) was 1.52 (95% confidence interval (CI): 1.17-1.97). The strength of this association is greater than individual MetS components such as elevated blood pressure (RR = 1.05, 95% CI: .72-1.52), elevated triglycerides (RR = 1.04, 95% CI: .84-1.29), low high-density lipoprotein cholesterol (RR = 1.16, 95% CI: .91-1.48), or obesity (RR = 1.12, 95% CI: .89-1.41). The risk of recurrent stroke was highest in the group with elevated glycemia (RR = 1.70, 95% CI: 1.12-2.56). CONCLUSIONS: This meta-analysis suggests that MetS might be an important predictor of recurrent stroke. Among the 5 components of MetS, elevated glycemia was a stronger predictor for recurrent stroke.

Metabolic syndrome and stroke: A meta-analysis of prospective cohort studies.

BACKGROUND AND AIM: The relationships between metabolic syndrome (MetS) and risk of incident stroke are inconsistent. We summarized the evidence by a meta-analysis of prospective cohort studies. METHODS AND RESULTS: We searched the PubMed, EMBASE, and Google Scholar databases from their inception until June 2016 for prospective cohort studies investigating this research question, relevant information was extracted by two independent investigators, and then aggregated using the fixed-effects models. We identified 16 studies, including 116,496 participants who were initially free of cardiovascular diseases. Comparing the persons without MetS, those with MetS have a significantly higher risk of incident stroke, and the pooled relative risk (RR) was 1.70 (95% confidence interval (CI): 1.49-1.95). Subgroup analyses suggested that women were more sensitive to this effect (with an RR of 1.83, 95% CI: 1.31-2.56) than men (RR=1.47 (95% CI: 1.22-1.78). And those with MetS have a significantly higher risk of ischemic stroke (RR=2.12, 95% CI: 1.46-3.08) than hemorrhagic stroke (RR=1.48, 95% CI: 0.98-2.24). CONCLUSIONS: This meta-analysis suggests that metabolic syndrome might be an important risk factor of stroke, particularly among women and those with ischemic stroke.