Gait disturbance is a manifestation of cerebral small vessel disease (CSVD). The posterolateral thalamus (PL), whose blood is mainly supplied by the P2 segment of posterior cerebral artery (P2-PCA), ...plays pivotal roles in gait regulation. We investigated the influence of the distance between P2-PCA and PL on gait with varying CSVD burden. 71 participants were divided into low and high CSVD burden groups. The distance from P2-PCA to PL was measured using 7 T TOF-MRA and categorized into an immediate or distant PCA-to-thalamus pattern. Functional connectivity (FC) and voxel-based morphometry were assessed to evaluate functional and structural alterations. In the low CSVD burden group, immediate PCA-to-thalamus supply strongly correlates with longer step length and higher wave phase time percent, and exhibited enhanced FCs in left supplementary motor area, right precentral cortex (PreCG.R). While in the high CSVD burden group, no association between PCA-to-thalamus pattern and gait was found, and we observed reduced FC in PreCG.R with immediate PCA-to-thalamus pattern. Higher CSVD burden was associated with decreased gray matter density in bilateral thalamus. However, no significant structural thalamic change was observed between the two types of PCA-to-thalamus patterns in all patients. Our study demonstrated patients with immediate PCA-to-thalamus supply exhibited better gait performance in low CSVD burden populations, which also correlated with enhanced FCs in motor-related cortex, indicating the beneficial effects of the immediate PCA-to-thalamus supply pattern. In the higher burden CSVD populations, the effects of PCA-to-thalamus pattern on gait are void, attributable to the CSVD-related thalamic destruction and impairment of thalamus-related FC.
BackgroundThe association between perivascular space (PVS) and white matter hyperintensity (WMH) has been unclear. Normal-appearing white matter (NAWM) around WMH is also found correlated with the ...development of focal WMH. This study aims to investigate the topological connections among PVS, deep WMH (dWMH) and NAWM around WMH using 7 Tesla (7T) MRI.MethodsThirty-two patients with non-confluent WMHs and 16 subjects without WMHs were recruited from our department and clinic. We compared the PVS burden between patients with and without WMHs using a 5-point scale. Then, the dilatation and the number of PVS within a radius of 1 cm around each dWMH were compared with those of a reference site (without WMH) in the contralateral hemisphere. In this study, we define NAWM as an area within the radius of 1 cm around each dWMH. Furthermore, we assessed the spatial relationship between dWMH and PVS.ResultsHigher PVS scores in the centrum semiovale were found in patients with >5 dWMHs (median 3) than subjects without dWMH (median 2, p = 0.014). We found there was a greater dilatation and a higher number of PVS in NAWM around dWMH than at the reference sites (p<0.001, p<0.001). In addition, 79.59% of the dWMHs were spatially connected with PVS.ConclusiondWMH, NAWM surrounding WMH and MRI-visible PVS are spatially correlated in the early stage of cerebral small vessel disease. Future study of WMH and NAWM should not overlook MRI-visible PVS.
Hyperhomocysteinemia, a risk factor for vascular disease, is associated with metabolic syndrome. Our study was aimed at exploring the effect of long-term hyperhomocysteinemia with metabolic ...disturbances on vascular remodeling. We also studied oxidative stress and expression of PPARγ in the coronary arteriole as a possible mechanism underlying vascular remodeling. Rats were treated with standard rodent chow (Control) or diet enriched in methionine (Met) for 48 weeks. Plasma homocysteine, blood glucose, serum lipids, malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) levels were measured. Coronary arteriolar and carotid arterial remodeling was assessed by histomorphometric techniques and the expression of PPARγ in vessel wall was investigated. In Met group, an increase in the level of fasting blood glucose, serum triglyceride, total cholesterol, MDA, and NO, a decline in the serum SOD level, and increased collagen deposition in coronary and carotid arteries were found. Moreover, we detected decreased expression of PPARγ in the coronary arterioles in Met group. In summary, our study revealed metabolic disturbances in this model of long-term hyperhomocysteinemia together with vascular remodeling and suggested that impaired oxidative stress, endothelium dysfunction, and decreased PPARγ expression in the vessel wall could be underlying mechanisms.
The involvement of land users, such as farmers and herders, is crucial in protecting ecosystems, and the Payment for Ecosystem Services (PES) is often regarded as a suitable measure to achieve this. ...Simultaneously, PES programs have sometimes failed to deliver on their stated aims. This article moots that livelihood capitals and policy credibility are important to consider in the implementation of PES programs. Livelihood capitals affect land users’ perceptions towards ecological protection, which in turn, affect policy credibility. To assess the relation between policy credibility and livelihood capitals, we developed a theoretical framework predicated upon the credibility thesis and the sustainable livelihoods approach. We constructed quantitative models for the measurement of credibility, and for the assessment of the relation between credibility and livelihood capitals. The models were applied to a Payment for Grassland Ecosystem Services (PGES) scheme implemented in Inner Mongolia, China. We thus were able to pinpoint the mechanisms that explain how policy credibility affects herders’ livelihood capitals and livelihoods. This study contributes to the research on PGES and pastoralism by: 1) delineating a new approach for studying the endogenous mechanisms of credibility in relation to livelihood capitals; 2) providing a theoretical and methodological basis that enables differentiating ecological conservation policies for various target groups (i.e. full-time, part-time, and non-agricultural herders); 3) presenting a selection of operational measures that may be used following the implementation of the Credibility Scales and Intervention (CSI) policy tool.
•Paper posits credibility and livelihood capitals are vital for PES programs.•Develops theoretical framework based on credibility thesis and SLA approach.•Puts forward method to measure credibility in relation to livelihood capitals.•Applied to Payment for Grassland Ecosystem Services in Inner Mongolia, China.•New methodological basis to differentiate PES policies for varying target groups.
•Mild hypothermia alleviates diabetes aggravated cerebral ischemic injury.•Mild hypothermia activates autophagy and inhibites pyroptosis in neuroprotection.•Mild hypothermia inhibites pyroptosis ...possibly via increasing autophagosomes.
Diabetic patients manifest with more severe neurological deficits than non-diabetes after ischemic stroke. It has been shown that hypothermia has neuroprotective effects on cerebral ischemia, but whether it is effective for cerebral ischemia in diabetic patients remains unknown. The aim of this study was to investigate whether hypothermia can alleviate cerebral ischemic injury in diabetic rats and the regulation of autophagy and pyroptosis of the treatment. We introduced permanent middle cerebral artery occlusion (pMCAO) in a model of type 2 diabetic rats prepared by high-fat diet combined with intraperitoneal injection of STZ in vivo and mimicked cerebral ischemia with diabetes by employing high glucose stimulation and oxygen–glucose deprivation/reoxygenation (OGD/R) in vitro. Moreover, 3-methyladenine and bafilomycin A1 were used to evaluate the association between autophagy and pyroptosis in vitro. Our results showed that diabetes aggravated neurological deficits, increased the volume of cerebral infarction and brain edema as well as the blood brain barrier permeability after cerebral ischemia, which were alleviated by mild hypothermia. Compared with the pMCAO model in non-diabetic rats and OGD/R model without high glucose stimulation in vitro, the expression of P62, NOD-like receptor protein 3 (NLRP3), cleaved caspase-1 and Gasdermin-N increased and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ decreased in the pMCAO model in diabetic rats and OGD/R model with high glucose stimulation, which could be reversed by mild hypothermia. In conclusion, mild hypothermia alleviated diabetes aggravated cerebral ischemic injury via activating autophagy and inhibiting pyroptosis.
This study was designed to evaluate antiplatelet effect and therapeutic effect of ginkgo diterpene lactone meglumine injection (GDLI) in acute ischemic stroke (AIS) patients. In this randomized, ...double‐blind, placebo‐controlled trial, we randomly assigned 70 inpatients within 48 hr after the onset of AIS to combination therapy with GDLI and aspirin (GDLI at a dose of 25 mg/d for 14 days plus aspirin at a dose of 100 mg/d for 90 days) or to placebo plus aspirin in a ratio of 1:1. Platelet function, the National Institute of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) were evaluated. A good outcome was defined as NIHSS scores decrease ≥5 or mRS scores decrease ≥2. Results showed that arachidonic acid induced maximum platelet aggregation rate (AA‐MAR) and mean platelet volume (MPV) of the GDLI‐aspirin group were much lower than that of the aspirin group (p = 0.013 and p = 0.034, respectively) after the 14‐day therapy. The combination of GDLI and aspirin was superior to aspirin alone, and had significant impact on the good outcome at day 90 (ORadj 7.21 95%CI, 1.03–50.68, p = 0.047). In summary, GDLI has antiplatelet effect and can improve the prognosis of AIS patients.
•ICH injury induces endoplasmic reticulum (ER) stress response.•Mild hypothermia could attenuate intracerebral hemorrhage (ICH) caused neuron injury by decreasing neuron apoptosis.•Mild hypothermia ...decreased ER response after ICH.
Mild hypothermia has been proved to reduce global and focal cerebral ischemic injury in rodents by preventing cellular apoptosis through several pathways. However, whether hypothermia will be beneficial for intracerebral hemorrhage (ICH) and its underlying mechanisms haven’t reached a consensus. It has been implicated that endoplasmic reticulum (ER) stress plays a role in the secondary injury after ICH in rats. In this study, we aimed to investigate whether mild hypothermia would attenuate ICH induced neuronal injury via regulating ER stress.
The model of ICH was induced by injecting autologous blood (120μl) into the rat striatum. Rats were divided into sham, normothermic (NT) and hypothermic (HT) groups. HT group were subjected to mild hypothermia (33°C–35°C) for 2days starting from 6h after ICH. Neurological deficits were evaluated. The ER stress related proteins (GRP78, CHOP and p-eIF2α) and the apoptosis associated indicators (cleaved caspase3, Bcl-2 and Bim) around hematoma were assessed by western blot, qRT-PCR (quantificational real-time polymerase chain reaction), immunofluorescence and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling) assay.
Neurological deficits following ICH were reduced in HT group compared to NT group. Protein levels of GRP78, CHOP and p-eIF2α significantly increased after ICH in both NT and HT group compared to sham group, which was consistent with the trend of cleaved-caspase3 at protein level, and Bim, Bcl-2 at gene level. In comparison to NT group, GRP78, CHOP, p-eIF2α, cleaved caspase-3 and Bim all decreased, while Bcl-2 increased in HT group. Additionally, apoptotic cells detected by TUNEL staining significantly decreased in the HT group.
Mild hypothermia could attenuate ICH caused neuron injury by decreasing ER response-induced neuron apoptosis.
Hyperhomocysteinemia, a risk factor for vascular disease, is associated with metabolic syndrome. Our study was aimed at exploring the effect of long-term hyperhomocysteinemia with metabolic ...disturbances on vascular remodeling. We also studied oxidative stress and expression of PPARgamma in the coronary arteriole as a possible mechanism underlying vascular remodeling. Rats were treated with standard rodent chow (Control) or diet enriched in methionine (Met) for 48 weeks. Plasma homocysteine, blood glucose, serum lipids, malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) levels were measured. Coronary arteriolar and carotid arterial remodeling was assessed by histomorphometric techniques and the expression of PPARgamma in vessel wall was investigated. In Met group, an increase in the level of fasting blood glucose, serum triglyceride, total cholesterol, MDA, and NO, a decline in the serum SOD level, and increased collagen deposition in coronary and carotid arteries were found. Moreover, we detected decreased expression of PPARgamma in the coronary arterioles in Met group. In summary, our study revealed metabolic disturbances in this model of long-term hyperhomocysteinemia together with vascular remodeling and suggested that impaired oxidative stress, endothelium dysfunction, and decreased PPARgamma expression in the vessel wall could be underlying mechanisms.
The widespread Early Cretaceous plutons intruding along the southern Great Xing'an Range (SGXR) provide evidence for tectonic evolution of the region. Petrological, geochemical, zircon U-Pb ...geochronology, and zircon Hf isotopic studies are conducted on intrusions from Bianjiadayuan and Hongling areas. These suites classify as A2-type granites and monzodiorites, respectively. The 138-133 Ma A2-type granites originated from partial melting of continental crustal materials at high temperatures and shallow depths with significant addition of juvenile mafic lower crust sourced from a metasomatized mantle. The 136-134 Ma monzodiorites originated from the partial melting of an enriched mantle that was modified by melts of a previously subducted slab coupled with crustal contamination. The Early Cretaceous magmatism in the SGXR occurred in two periods: ∼145-136 Ma (peak at ∼139 Ma; εHf (t) = 5 to 10) and ∼136-130 Ma (peak at ∼131 Ma; εHf (t) = -10 to 15). The Early Cretaceous granite-monzodiorite suite in the SGXR suggests a bimodal magmatism in an extensional setting. The ∼145-130 Ma magmatism may have been triggered by asthenospheric upwelling induced by the Mongol-Okhotsk oceanic slab breakoff and large-scale lithospheric delamination resulting from post-orogenic extension. The variation of subduction direction of the Paleo-Pacific Ocean likely triggered a change in stress regime at ca. 136 Ma and likely promoted the lithospheric delamination beneath the SGXR resulting in intense magmatism originating from various sources. As such, the Paleo-Pacific Oceanic subduction likely played an important role in the Early Cretaceous magmatism in the SGXR.
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