Intra-arterial verapamil improves functional outcomes of thrombectomy in a preclinical model of extended hyperglycemic stroke

The abrupt hyperglycemic reperfusion following thrombectomy has been shown to harm the efficacy of the intervention in stroke patients with large vessel occlusion. Studies of ours and others have shown thioredoxin-interacting protein (TXNIP) is critically involved in hyperglycemic stroke injury. We recently found verapamil ameliorates cerebrovascular toxicity of tissue plasminogen activators in hyperglycemic stroke. The present study aims to answer if verapamil exerts direct neuroprotective effects and alleviates glucose toxicity following thrombectomy in a preclinical model of hyperglycemic stroke. Primary cortical neural (PCN) cultures were exposed to hyperglycemic reperfusion following oxygen-glucose deprivation (OGD), with or without verapamil treatment. In a mouse model of intraluminal stroke, animals were subjected to 4 h middle cerebral artery occlusion (MCAO) and intravenous glucose infusion. Glucose infusion lasted one more hour at reperfusion, along with intra-arterial (i.a.) verapamil infusion. Animals were subjected to sensorimotor function tests and histological analysis of microglial phenotype at 72 h post-stroke. According to our findings, glucose concentrations (2.5–20 mM) directly correlated with TXNIP expression in OGD-exposed PCN cultures. Verapamil (100 nM) effectively improved PCN cell neurite growth and reduced TXNIP expression as well as interaction with NOD-like receptor pyrin domain-containing-3 (NLRP3) inflammasome, as determined by immunoblotting and immunoprecipitation. In our mouse model of extended hyperglycemic MCAO, i.a. verapamil (0.5 mg/kg) could attenuate neurological deficits induced by hyperglycemic stroke. This was associated with reduced microglial pro-inflammatory transition. This finding encourages pertinent studies in hyperglycemic patients undergoing thrombectomy where the robust reperfusion may exacerbate glucose toxicity

Experimental investigation on the effect of wear flat inclination on the cutting response of a blunt tool in rock cutting

A vast majority of experimental researches focuses on the cutting action of a sharp cutter, while there has been limited experimental work devoted to the study of the contact process at the wear flat-rock interface. The specific objective of this study is to determine the effect of the wear flat inclination angle ( β ) with respect to the cutter velocity vector ( vv ) on both the contact stress ( σ ) and friction coefficient ( μ ) mobilized at the wear flat-rock interface. An extensive and comprehensive set of cutting experiments was carried out on thirteen different sedimentary quarry rock samples using a state-of-the-art rock cutting equipment. A unique cutter holder was purposely designed and manufactured along with a precise experimental protocol implemented in order to change the back rake angle and therefore the inclination β by steps of 0.10∘ . The experimental observations confirm the existence of three regimes of frictional contact (identified as elastic, elasto-plastic and plastic) for all rock samples. Further, the results suggest that the scaled contact stress is predominantly controlled by a dimensionless number η=E∗tanβq with E∗ the plane strain elastic modulus and q the rock strength

An application of linearised dimensional analysis to rock cutting

Three linearized predictive models are presented: one from the sandstone and marble data; one from the sandstone data; and one from the marble data. These three models allow modifications as the experimental program progresses. Further, these models are shown to be useful for predicting the machine reaction forces under a variety of test conditions

Influence of surface roughness on the scatter in hardness measurements - A numerical study

Indentation hardness is usefully applied in the field of rock comminution, where high contact stresses are commonly encountered. Hardness measurements pro- vide a means for estimating the discontinuity wall strength which is required to understand the shear strength of the discontinuity. The hardness value is also used to estimate compressive strength of rocks with known density

Endocan as a marker of endothelial dysfunction in hypertension: a systematic review and meta-analysis

Hypertension is one of the foremost risk factors for cardiovascular disease and a significant cause of death worldwide. Importantly, endothelial dysfunction (ED) is one of the primary manifestations that may precede the development of hypertension. Endocan is a novel endothelial dysfunction and inflammation biomarker secreted from endothelial cells. Whether endocan may serve as a biomarker of hypertension is currently debated. This systematic review and meta-analysis aimed at linking endocan to ED in hypertensive patients. International databases, including PubMed, Scopus, Embase, and Web of Science, were systematically searched for studies investigating Endocan serum or plasma levels in hypertensive patients and healthy controls. Random effect meta-analysis was performed to calculate the standardized mean difference (SMD) and 95% confidence interval (CI). A total of 20 studies assessing the association between endocan levels and hypertension were included in which 3130 individuals with a mean age of 50.48 ± 8.45 years were assessed. Hypertensive patients presented with higher circulating endocan levels (SMD 0.91, 95% CI 0.44-1.38, p-value < 0.01) compared with healthy controls. Interestingly, our data demonstrated that removing three studies assessing endocan levels in hypertensive patients with different comorbidities or special populations resulted in the same statistically higher endocan levels (SMD 1.16, 95% CI 0.66-1.65, p-value < 0.01). Overall, this systematic review and meta-analysis indicated that in hypertensive patients circulating endocan levels are significantly elevated. Thus, suggesting endocan as an easy-to-use biomarker to detect ED in hypertension. Despite this, more research is warranted to address this potential ability specifically

Image1_Intra-arterial verapamil improves functional outcomes of thrombectomy in a preclinical model of extended hyperglycemic stroke.PDF

The abrupt hyperglycemic reperfusion following thrombectomy has been shown to harm the efficacy of the intervention in stroke patients with large vessel occlusion. Studies of ours and others have shown thioredoxin-interacting protein (TXNIP) is critically involved in hyperglycemic stroke injury. We recently found verapamil ameliorates cerebrovascular toxicity of tissue plasminogen activators in hyperglycemic stroke. The present study aims to answer if verapamil exerts direct neuroprotective effects and alleviates glucose toxicity following thrombectomy in a preclinical model of hyperglycemic stroke. Primary cortical neural (PCN) cultures were exposed to hyperglycemic reperfusion following oxygen-glucose deprivation (OGD), with or without verapamil treatment. In a mouse model of intraluminal stroke, animals were subjected to 4 h middle cerebral artery occlusion (MCAO) and intravenous glucose infusion. Glucose infusion lasted one more hour at reperfusion, along with intra-arterial (i.a.) verapamil infusion. Animals were subjected to sensorimotor function tests and histological analysis of microglial phenotype at 72 h post-stroke. According to our findings, glucose concentrations (2.5–20 mM) directly correlated with TXNIP expression in OGD-exposed PCN cultures. Verapamil (100 nM) effectively improved PCN cell neurite growth and reduced TXNIP expression as well as interaction with NOD-like receptor pyrin domain-containing-3 (NLRP3) inflammasome, as determined by immunoblotting and immunoprecipitation. In our mouse model of extended hyperglycemic MCAO, i.a. verapamil (0.5 mg/kg) could attenuate neurological deficits induced by hyperglycemic stroke. This was associated with reduced microglial pro-inflammatory transition. This finding encourages pertinent studies in hyperglycemic patients undergoing thrombectomy where the robust reperfusion may exacerbate glucose toxicity.</p