Serum Uric Acid Levels Are Associated With Macula Microvasculature Changes In Hypertensive White Matter Hyperintensity Patients.

PURPOSE: To characterize the macula microvasculature using fractal dimension (FD) in hypertensive white matter hyperintensity (WMH) participants and explore the association between the microvascular changes and serum uric acid levels. METHODS: Thirty-eight WMH participants were dementia and stroke-free, and 37 healthy controls were enrolled. Optical coherence tomographic angiography (OCTA) was used to image the superficial vascular complex (SVC), deep vascular complex (DVC), and inner vascular complex (IVC) in a 2.5-mm diameter concentric circle (excluding the foveal avascular zone FAZ). A commercial algorithm was used to quantify the complexity and density of the three capillary layers by fractal analysis. RESULTS: WMH participants showed significantly lower FD value in the SVC (P = 0.002), DVC (P < 0.001) and IVC (P = 0.012) macula microvasculature compared with control group. After adjusting for risk factors (hypertension, diabetes, age and gender) SVC (P = 0.035) and IVC (P = 0.030) significantly correlated with serum uric acid. CONCLUSION: Serum uric acid levels are associated with microvascular changes in WMH. Fractal dimension based on OCTA imaging could help quantitatively characterize the macula microvasculature changes in WMH and may be a potential screening tool to detect serum uric acid level changes.

Irregular degree centrality in neuromyelitis optica spectrum disorder patients with optic neuritis: A resting-state functional magnetic resonance imaging study.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disorder that causes significant changes in brain connectivity and visual impairment. Degree centrality (DC), a graph-based assessment of network organization was performed to explore the connectivity changes in NMOSD patients and their correlation with clinical consequences. METHODS: Twenty-two NMOSD patients and 22 healthy controls (HC) were included. Participants underwent visual acuity examination and resting-state functional magnetic resonance imaging (fMRI) of the brain. We first performed DC analysis to identify voxels that showed changes in whole-brain functional connectivity (FC) with other voxels. DC was calculated by the fMRI graph method and comparison between the two groups was done by two-sample t-test. GraphPad Prism was used to assess the association between DC changes and clinical consequences. RESULTS: Out of the 22 NMOSD patients, 7 (31.82%) had ON once while 15 (68.18%) had ON twice or more. Decreased DC value (P < 0.001) in the left frontal superior orbital gyrus (ORBsup), left angular gyrus (ANG) and right parietal superior gyrus (SPG) was found in NMOSD patients when compared with healthy controls respectively. Reduced visual acuity significantly correlated (R2 = 0.212, P = 0.040) with DC values in SPG while the frequency of ON significantly correlated (R2 = 0.04, P = 0.040) with DC values in the ANG in NMOSD patients. CONCLUSIONS: NMOSD patients experience neural network dysfunction which may be associated with their clinical implications.

Superficial Macula Capillary Complexity Changes Are Associated With Disability in Neuromyelitis Optica Spectrum Disorders.

Purpose: We examined the macular microvascular changes of the macula in neuromyelitis optica spectrum disorder (NMOSD) patients and its association with their disability and other clinical variables. Methods: Thirty-four NMOSD (13 patients without optic neuritis, NMOSD-NON, and 21 patients with a history of optic neuritis, NMOSD-ON) and 44 healthy controls (HCs) were included in the study. Optical coherence tomographic angiography (OCTA) was used to image the superficial (SCP), deep (DCP), and whole capillary plexus (WCP) in a 2.5-mm-diameter concentric circle [excluding the foveal avascular zone (FAZ)]. An algorithm (Dbox) was used to quantify the complexity of the three capillary layers by fractal analysis. We also evaluated the expanded disability scale status (EDSS). Results: Dbox values were significantly reduced in SCP (p < 0.001), DCP (p < 0.001), and WCP (p = 0.003) of NMOSD when compared with HCs. Dbox values were significantly reduced in NMOSD eyes with optic neuritis when compared with healthy controls (p < 0.001) and eyes without optic neuritis (p = 0.004) in the SCP. In the DCP, eyes with optic neuritis showed significantly reduced Dbox values when compared with eyes without optic neuritis (p = 0.016) and healthy controls (p < 0.001); eyes without optic neuritis showed significantly reduced Dbox values (p = 0.007) in the DCP when compared with healthy controls. A significant negative correlation (Rho = -0.475, p = 0.005) was shown between the superficial macula Dbox values and the EDSS in NMOSD patients. Additionally, a negative correlation (Rho = -0.715, p = 0.006) was seen in the superficial Dbox values in [e]eyes without optic neuritis and EDSS. Conclusions: Macular microvascular damage in the superficial plexus is associated with disability in NMOSD. Macular microvascular alterations arise independently of the occurrence of ON in NMOSD.

Pannexin1 Channel Inhibitor (10panx) Protects Against Transient Focal Cerebral Ischemic Injury by Inhibiting RIP3 Expression and Inflammatory Response in Rats.

BACKGROUND: Recent studies have demonstrated that programmed necrosis (necroptosis) is a delayed component of ischemic neuronal injury and our previous study has shown that pannexin 1 channel is involved in cerebral ischemic injury and cellular inflammatory response. Here, we examined whether the pannexin 1 channel inhibitor, 10panx, could reduce focal ischemic brain injury in rats by inhibiting cellular necroptosis and the associated inflammation. Male Sprague-Dawley rats were randomly divided into sham-operated, MCAO (transient middle cerebral artery occlusion) group, and 10panx-treated groups. We investigated the effect of 10panx by assessing infarct volume and neurological deficit. Further, we determined the potential mechanism using immunofluorescent staining, Western blotting, enzyme-linked immunosorbent assay (ELISA) and TUNEL assay. We demonstrated that 10panx reduced infarct volume and alleviated neurological deficit in the MCAO injury model. 10panx ameliorated post-ischemic neuronal death, but it did not reduce the TUNEL positive neurons and expression of cleaved-caspase3. In contrast, expression of necroptosis related protein receptor-interacting protein 3 (RIP3) was significantly decreased. Furthermore, 10panx reduced the release of high mobility group box 1 (HMGB1) from neurons and inhibited microglial activation and secretion of pro-inflammatory factors. Immunent co-labeling of RIP3 with HMGB1 showed that RIP3 protein was closely related with the release of HMGB1 from nucleus to cytoplasm. Our data suggested that 10panx treatment may ameliorate MCAO injury by reducing RIP3-mediated necroptosis, HMGB1 release and associated inflammatory response. RIP3 may play an important role in the release of HMGB1 and inflammation after stroke.

Prediction of poor outcome after hypoxic-ischemic brain injury by diffusion-weighted imaging: A systematic review and meta-analysis.

Accurate prediction of the neurological outcome following hypoxic-ischemic brain injury (HIBI) remains difficult. Diffusion-weighted imaging (DWI) can detect acute and subacute brain abnormalities following global cerebral hypoxia. Therefore, DWI can be used to predict the outcomes of HIBI. To this end, we searched the PubMed, EMBASE, and Cochrane Library databases for studies that examine the diagnostic accuracy of DWI in predicting HIBI outcomes in adult patients between January1995 and September 2019. Next, we conducted a comprehensive meta-analysis using the Meta-DiSc and several complementary techniques. Following the application of inclusion and exclusion criteria, a total of 28 studies were included with 98 data subsets. The overall sensitivity and specificity, with 95% confidence interval, were 0.613(0.599-0.628) and 0.958(0.947-0.967), respectively, and the area under the curve was 0.9090. Significant heterogeneity among the included studies and a threshold effect were observed (p<0.001). Different positive indices were the major sources for the heterogeneity, followed by the anatomical region examined, both of which significantly affected the prognostic accuracy. In conclusion, we demonstrated that DWI can be an instrumental modality in predicting the outcome of HIBI with good prognostic accuracy. However, the lack of clear and generally accepted positive indices limits its clinical application. Therefore, using more reliable positive indices and combining DWI with other clinical predictors may improve the diagnostic accuracy of HIBI.