Mechanisms of Flow-Mediated Dilation of Pial Collaterals and the Effect of Hypertension

Hypertension ◽  
2021 ◽  
Author(s):  
Zhaojin Li ◽  
Marilyn J. Cipolla
Keyword(s):  
Shear Stress ◽  
Ischemic Stroke ◽  
Transient Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Chronic Hypertension ◽  
Collateral Flow ◽  
Hypertensive Rats ◽  
Vessel Occlusion ◽  
Stroke Treatment ◽  
Luminal Flow

Leptomeningeal anastomoses are small distal anastomotic vessels also known as pial collaterals in the brain. These vessels redirect blood flow during an occlusion and are important for stroke treatment and outcome. Pial collaterals have unique hemodynamic forces and experience significantly increased luminal flow and shear stress after the onset of ischemic stroke. However, there is limited knowledge of how pial collaterals respond to flow and shear stress, and whether this response is altered in chronic hypertension. Using an in vitro system, pial collaterals from normotensive and hypertensive rats (n=6–8/group) were isolated and luminal flow was induced with intravascular pressure maintained at 40 mm Hg. Collateral lumen diameter was measured following each flow rate in the absence or presence of pharmacological inhibitors and activators. Collaterals from male and female Wistar rats dilated similarly to increased flow (2 µL/minute: 58.4±18.7% versus 67.9±7.4%; P =0.275), and this response was prevented by inhibition of the transient receptor potential vanilloid type 4 channel, as well as inhibitors of nitric oxide and intermediate-conductance calcium-activated potassium channels, suggesting shear stress-induced activation of this pathway was involved. However, the vasodilation was significantly impaired in hypertensive rats (2 µL/minute: 17.7±7.7%), which was restored by inhibitors of reactive oxygen species and mimicked by angiotensin II. Thus, flow- and shear stress-induced vasodilation of pial collaterals appears to be an important stimulus for increasing collateral flow during large vessel occlusion. Impairment of this response during chronic hypertension may be related to poorly engaged pial collaterals during ischemic stroke in hypertensive subjects.

scholarly journals Evodiamine Induces Transient Receptor Potential Vanilloid-1-Mediated Protective Autophagy in U87-MG Astrocytes

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Ann-Jeng Liu ◽  
Sheng-Hao Wang ◽  
Sz-Ying Hou ◽  
Chien-Ju Lin ◽  
Wen-Ta Chiu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Extracellular Calcium ◽  
Motor Dysfunction ◽  
Transient Receptor Potential Vanilloid ◽  
Jnk Pathway ◽  
Mortality And Morbidity ◽  
Stroke Treatment ◽  
Transient Receptor

Cerebral ischemia is a leading cause of mortality and morbidity worldwide, which results in cognitive and motor dysfunction, neurodegenerative diseases, and death. Evodiamine (Evo) is extracted fromEvodia rutaecarpaBentham, a plant widely used in Chinese herbal medicine, which possesses variable biological abilities, such as anticancer, anti-inflammation, antiobesity, anti-Alzheimer’s disease, antimetastatic, antianoxic, and antinociceptive functions. But the effect of Evo on ischemic stroke is unclear. Increasing data suggest that activation of autophagy, an adaptive response to environmental stresses, could protect neurons from ischemia-induced cell death. In this study, we found that Evo induced autophagy in U87-MG astrocytes. A scavenger of extracellular calcium and an antagonist of transient receptor potential vanilloid-1 (TRPV-1) decreased the percentage of autophagy accompanied by an increase in apoptosis, suggesting that Evo may induce calcium-mediated protective autophagy resulting from an influx of extracellular calcium. The same phenomena were also confirmed by a small interfering RNA technique to knock down the expression of TRPV1. Finally, Evo-induced c-Jun N-terminal kinases (JNK) activation was reduced by a TRPV1 antagonist, indicating that Evo-induced autophagy may occur through a calcium/c-Jun N-terminal kinase (JNK) pathway. Collectively, Evo induced an influx of extracellular calcium, which led to JNK-mediated protective autophagy, and this provides a new option for ischemic stroke treatment.

scholarly journals The Synergistic Effect of TRPV1 on Oxidative Stress-Induced Autophagy and Apoptosis in Microglia

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Tingting Huang ◽  
Yao Lin ◽  
Qiongyi Pang ◽  
Weimin Shen ◽  
Xiang Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Glucose Deprivation ◽  
Transient Receptor Potential Vanilloid ◽  
Stress Injury ◽  
Stroke Treatment ◽  
Transmission Electron ◽  
Transient Receptor

Stroke mostly including ischemic stroke is the second leading mortality and disability worldwide. Oxidative stress injury occurred during ischemic stroke treatment generally. A high amount of reactive oxygen species (ROS) is involved in oxidative stress induction. Transient receptor potential vanilloid 1 (TRPV1) has been shown to regulate oxidative stress and apoptosis in microglia; however, the detailed mechanisms remain unclear. We aimed to explore whether autophagy-regulated oxidative stress and apoptosis are associated with TRPV1. The model of oxygen and glucose deprivation (OGD/R) in microglia was established. The siRNA of Atg5 and inhibitors and agonists of both autophagy and TRPV1 were involved in our study. Autophagy-related markers Atg5, LC3II/LC3I, and Beclin-1 were measured, and the autophagosome was observed under a transmission electron microscope (TEM). Caspase 3 was detected using ELISA. ROS and JC-1 were detected using flow cytometry. Apoptosis was observed by TUNEL. The results indicated that oxidative stress-induced injury and apoptosis may be impeded by the increasing autophagy, and TRPV1 inhibition could suppress the OGD/R-induced autophagy of microglia. However, the effect of TRPV1’s inhibitor on oxidative stress and apoptosis was not obvious when the autophagy was blocked. These findings suggested that TRPV1 may exhibit antioxidative and antiapoptosis effect on OGD/R-induced microglia. However, the experimental results do not fully demonstrate that the TRPV1-mediated antioxidative and antiapoptosis effect is through the affecting autophagy entirely.

scholarly journals Cerebral endothelial cell-derived small extracellular vesicles enhance neurovascular function and neurological recovery in rat acute ischemic stroke models of mechanical thrombectomy and embolic stroke treatment with tPA

2021 ◽  
pp. 0271678X2199298
Author(s):  
Chao Li ◽  
Chunyang Wang ◽  
Yi Zhang ◽  
Owais K Alsrouji ◽  
Alex B Chebl ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Extracellular Vesicles ◽  
Mechanical Thrombectomy ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Therapeutic Effects ◽  
Vessel Occlusion ◽  
Healthy Human ◽  
Stroke Treatment

Treatment of patients with cerebral large vessel occlusion with thrombectomy and tissue plasminogen activator (tPA) leads to incomplete reperfusion. Using rat models of embolic and transient middle cerebral artery occlusion (eMCAO and tMCAO), we investigated the effect on stroke outcomes of small extracellular vesicles (sEVs) derived from rat cerebral endothelial cells (CEC-sEVs) in combination with tPA (CEC-sEVs/tPA) as a treatment of eMCAO and tMCAO in rat. The effect of sEVs derived from clots acquired from patients who had undergone mechanical thrombectomy on healthy human CEC permeability was also evaluated. CEC-sEVs/tPA administered 4 h after eMCAO reduced infarct volume by ∼36%, increased recanalization of the occluded MCA, enhanced cerebral blood flow (CBF), and reduced blood-brain barrier (BBB) leakage. Treatment with CEC-sEVs given upon reperfusion after 2 h tMCAO significantly reduced infarct volume by ∼43%, and neurological outcomes were improved in both CEC-sEVs treated models. CEC-sEVs/tPA reduced a network of microRNAs (miRs) and proteins that mediate thrombosis, coagulation, and inflammation. Patient-clot derived sEVs increased CEC permeability, which was reduced by CEC-sEVs. CEC-sEV mediated suppression of a network of pro-thrombotic, -coagulant, and -inflammatory miRs and proteins likely contribute to therapeutic effects. Thus, CEC-sEVs have a therapeutic effect on acute ischemic stroke by reducing neurovascular damage.

Transient receptor potential vanilloid 2‐mediated shear‐stress responses in C2C12 myoblasts are regulated by serum and extracellular matrix

2015 ◽  
Vol 29 (11) ◽  
pp. 4726-4737 ◽  
Author(s):  
Felix Kurth ◽  
Alfredo Franco‐Obregón ◽  
Marco Casarosa ◽  
Simon K. Küster ◽  
Karin Wuertz‐Kozak ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Shear Stress ◽  
Stress Responses ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
C2c12 Myoblasts ◽  
Transient Receptor

scholarly journals Racial Differences in Mechanical Thrombectomy Utilization for Ischemic Stroke in the United States

2020 ◽  
Vol 30 (1) ◽  
pp. 91-96 ◽  
Author(s):  
Charles Esenwa ◽  
Alain Lekoubou ◽  
Kinfe G. Bishu ◽  
Kemar Small ◽  
Ava Liberman ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Racial Differences ◽  
Population Sample ◽  
Standard Of Care ◽  
Stroke Care ◽  
The United States ◽  
Vessel Occlusion ◽  
Stroke Treatment ◽  
Nationally Representative ◽  
Adjusted Model

Background: Compared with non-Hispanic Whites (NHW), racial-ethnic minorities bear a disproportionate burden of stroke and receive fewer evidence-based stroke care processes and treatments. Since 2015, me­chanical thrombectomy (MT) has become standard of care for acute ischemic stroke (AIS) patients with proximal anterior circula­tion large vessel occlusion (LVO).Objectives: Our objectives were to: assess recent trends in nationwide MT utilization among patients with AIS; determine if there were racial differences; and identify what factors were associated with such differ­ences.Methods: We performed a retrospective cohort study using nationally representative data of a non-institutionalized population sample from 2006 to 2014 obtained from the Nationwide Inpatient Sample (NIS). We identified a total of 889,309 observations of AIS, of which there were 5,256 MT observa­tions.Results: In the fully adjusted model, rate of thrombectomy utilization was significantly lower in African Americans (AA) (OR .67, CI .58-.76, P<.001) compared with NHW and Hispanics (OR .94, CI .78-1.13, P=.5).Conclusion: We found a significant dispar­ity in MT utilization for AA compared with NHW and Hispanics. More work is needed to understand the drivers of this racial disparity in stroke treatment. Ethn Dis. 2020;30(1):91-96; doi:10.18865/ed.30.1.91

‘Stroke Room': Diagnosis and Treatment at a Single Location for Rapid Intraarterial Stroke Treatment

2015 ◽  
Vol 40 (5-6) ◽  
pp. 251-257 ◽  
Author(s):  
Andreas Ragoschke-Schumm ◽  
Umut Yilmaz ◽  
Panagiotis Kostopoulos ◽  
Martin Lesmeister ◽  
Matthias Manitz ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Treatment Time ◽  
Diagnosis And Treatment ◽  
Vessel Occlusion ◽  
Stroke Treatment ◽  
Single Location ◽  
Before And After ◽  
Therapeutic Procedures ◽  
Therapeutic Measures

Background: For patients with acute ischemic stroke, intra-arterial treatment (IAT) is considered to be an effective strategy for removing the obstructing clot. Because outcome crucially depends on time to treatment (‘time-is-brain' concept), we assessed the effects of an intervention based on performing all the time-sensitive diagnostic and therapeutic procedures at a single location on the delay before intra-arterial stroke treatment. Methods: Consecutive acute stroke patients with large vessel occlusion who obtained IAT were evaluated before and after implementation (April 26, 2010) of an intervention focused on performing all the diagnostic and therapeutic measures at a single site (‘stroke room'). Result: After implementation of the intervention, the median intervals between admission and first angiography series were significantly shorter for 174 intervention patients (102 min, interquartile range (IQR) 85-120 min) than for 81 control patients (117 min, IQR 89-150 min; p < 0.05), as were the intervals between admission and clot removal or end of angiography (152 min, IQR 123-185 min vs. 190 min, IQR 163-227 min; p < 0.001). However, no significant differences in clinical outcome were observed. Conclusion: This study shows for the, to our knowledge, first time that for patients with acute ischemic stroke, stroke diagnosis and treatment at a single location (‘stroke room') saves crucial time until IAT.

scholarly journals ADAPT technique with ACE68 and ACE64 reperfusion catheters in ischemic stroke treatment: results from the PROMISE study

2018 ◽  
Vol 11 (3) ◽  
pp. 226-231 ◽  
Author(s):  
Peter Schramm ◽  
Pedro Navia ◽  
Rosario Papa ◽  
Joaquin Zamarro ◽  
Alejandro Tomasello ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Randomized Trials ◽  
Similar Efficacy ◽  
Anterior Circulation ◽  
Vessel Occlusion ◽  
Serious Adverse Events ◽  
Clinical Trial Registration ◽  
Aspiration Thrombectomy ◽  
Stroke Treatment ◽  
Post Procedure

Background and purposeThe recent randomized trials demonstrated the benefit of mechanical thrombectomy in stroke therapy. However, treatment using different strategies is an ongoing area of investigation. The PROMISE study analyzed the safety and effectiveness of the Penumbra System with the ACE68 and ACE64 reperfusion catheters in aspiration thrombectomy of stroke, using A Direct Aspiration First Pass Technique (ADAPT).MethodsPROMISE was a prospective study which enrolled 204 patients with intracranial anterior circulation large vessel occlusion (LVO) ischemic stroke in 20 centers from February 2016 to May 2017. Initial treatment was with the ACE68/ACE64 catheters within 6 hours of symptom onset. Imaging and safety review was performed by an independent Core Laboratory and a Clinical Events Committee. The primary angiographic outcome was revascularization to mTICI 2b-3 at immediate post-procedure and the primary clinical outcome was 90-day modified Rankin Scale (mRS) score ≤2. Safety assessment included device- and procedure-related serious adverse events (SAEs), symptomatic intracranial hemorrhage (sICH), mortality, and embolization of new territory (ENT).ResultsEnrolled patients had a median age of 74 (IQR 65–80) years and a median admission NIHSS of 16 (IQR 11–20). The post-procedure mTICI 2b-3 revascularization rate was 93.1% and the 90-day mRS 0–2 rate was 61%. Device- and procedure-related SAEs at 24 hours occurred in 1.5% and 3.4%, respectively, 90-day mortality was 7.5%, sICH occurred in 2.9% while ENT occurred in 1.5%.ConclusionsFor frontline therapy of LVO stroke, the ACE68/ACE64 catheters for aspiration thrombectomy were found to be safe and showed similar efficacy to randomized trials using other revascularization techniques.Clinical Trial RegistrationNCT02678169; Pre-results.

scholarly journals Downregulation of endothelial transient receptor potential vanilloid type 4 channel underlines impaired endothelial nitric oxide-mediated relaxation in the mesenteric arteries of hypertensive rats

2019 ◽  
pp. 219-231 ◽  
Author(s):  
A. Boudaka ◽  
M. Al-Suleimani ◽  
I. Al-Lawati ◽  
H. Baomar ◽  
S. Al-Siyabi
Keyword(s):  
Nitric Oxide ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Mesenteric Arteries ◽  
Transient Receptor Potential Vanilloid ◽  
Positive Staining ◽  
Hypertensive Rats ◽  
Transient Receptor ◽  
Endothelial Nitric Oxide ◽  
Trpv4 Channel

The endothelium contributes to the maintenance of vasodilator tone by releasing endothelium-derived relaxing factors, including nitric oxide (NO). In hypertension, endothelial nitric oxide synthase (eNOS) produces less NO and could be one of the contributing factors to the increased peripheral vascular resistance. Agonist-induced Ca(2+) entry is essential for the activation of eNOS. The transient receptor potential vanilloid type 4 (TRPV4) channel, a Ca(2+)-permeant cation channel, is expressed in the endothelial cells and involved in the regulation of vascular tone. The present study aimed to investigate the role of TRPV4 channel in endothelium-dependent NO-mediated relaxation of the resistance artery in hypertensive rats. Using a wire myograph, relaxation response to the TRPV4 activator, 4alpha-phorbol-12,13-didecanoate (4alphaPDD) was assessed in mesenteric arteries obtained from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs). Compared to WKY, SHR demonstrated a significantly attenuated 4alphaPDD-induced endothelium-dependent NO-mediated relaxation. Immunohistochemical analysis revealed positive staining for TRPV4 in the endothelium of mesenteric artery sections in both WKY and SHR. Furthermore, TRPV4 mRNA and protein expressions in SHR were significantly lower than their expression levels in WKY rats. We conclude that 4alphaPDD-induced endothelium-dependent NO-mediated vasorelaxation is reduced in SHR and downregulation of TRPV4 could be one of the contributing mechanisms.

Abstract TP6: Factors Influencing Infarct Progression During Ischemic Stroke Patients Transfer: Collaterals Lost is Brain Lost

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Gregoire Boulouis ◽  
Arne Lauer ◽  
Ahmer Khawdja Siddiqui ◽  
Andreas Charidimou ◽  
Robert Regenhardt ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Vascular Occlusion ◽  
Time Interval ◽  
Stroke Severity ◽  
Collateral Flow ◽  
Stroke Patients ◽  
Vessel Occlusion ◽  
Main Determinants ◽  
Initial Score ◽  
Stroke Center

Introduction: When transferred from a referring hospital (RH) to a thrombectomy capable stroke center (TCSC), patients with initially favorable imaging profile (ASPECT score ≥6) often demonstrate infarct progression significant enough to make them ineligible at arrival. We sought to determine the clinical and imaging factors associated with this phenomenon in transferred ischemic stroke patients. Methods: We identified adult stroke patients transferred from one of 30 RH between 2010 and 2016 for which (1) a RH computed tomography (CT) and (2) a CT Angiography (CTA) at arrival were available for review. ASPECT scores were evaluated by 2 raters. The adequacy of leptomeningeal collateral flow was rated as none/poor, decreased, adequate or augmented per the Maas et al (Stroke 2009), modified scale. ASPECTS decay was defined as an ASPECT initial score ≥6 worsening between RH and TCSC CTs to a score <6. Results: A total of 330 patients were included in the analysis (mean age 70.2 ± 14.2, 43.3% females). Univariable subgroup analyses showed that patients with ASPECTs decay were more likely to be females (55% vs 40%, p=0.02), not on anticoagulants (4% vs 15%, p=0.01), and with higher initial NIHSS (Median [IQR] 19 [15.3-22] vs 11 [6-17], p<0.001), hyperdense vessel sign on initial CT (71% vs 26%, p<0.001) and poor collaterals on CTA (72% vs 19%, p<0.001). In multivariable models, higher NIHSS, lower baseline ASPECTs, CTA evidence of a proximal occlusion, and none/poor collaterals were strong predictors of ASPECTs decay, with collateral status demonstrating the highest odds ratio (aOR 10.3, 95%CI: [4.1-29], p<0.001). Similar results were found after stratification by vessel occlusion level. Conclusion: In ischemic stroke patients transferred for thrombectomy, poor collateral flow, stroke severity and proximal vascular occlusion, but not time interval, are the main determinants of ASPECTs decay.

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