Hypoxia-specific anti-RAGE exosomes for nose-to-brain delivery of anti-miR-181a oligonucleotide in an ischemic stroke model

Nanoscale ◽  
2021 ◽  
Author(s):  
Minkyung Kim ◽  
Youngki Lee ◽  
Minhyung Lee
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Cerebral Arteries ◽  
Brain Delivery ◽  
Stroke Model ◽  
Thrombolytic Agents ◽  
The Brain

Ischemic stroke is caused by a reduction in blood flow to the brain due to narrowed cerebral arteries. Thrombolytic agents have been used to induce reperfusion of occluded cerebral arteries....

scholarly journals Influence of different qualitative composition of infusion solutions on cerebral hemodynamics in patients with acute ischemic stroke

2020 ◽  
Vol 73 (2) ◽  
pp. 272-277
Author(s):  
Andrii I. Semenenko ◽  
Halyna I. Khrebtii ◽  
Svetlana L. Malyk ◽  
Dmytro V. Dmytriiev ◽  
Roksolana Ya. Bodnar ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Ischemic Stroke ◽  
Cerebral Arteries ◽  
Cerebral Hemodynamics ◽  
Control Group ◽  
Qualitative Composition ◽  
Infusion Solution ◽  
Brain Substance ◽  
The Brain

The aim: Investigate the effect of 0.9% NaCl, HES 130, HAES-LX-5% and mannitol 15% on cerebral hemodynamics in patients with AIS. Materials and methods: The study included 100 patients with AIS. As the investigated solutions were used: isosmolar 0.9% NaCl, hyperosmolar mannitol 15%, colloid-isoosmolar HES 130, colloid-hyperosmolar HAES-LX-5%. The control group received only 0.9% NaCl compared: 0.9% NaCl+HES 130, 0.9% NaCl+HAES-LX-5%, 0.9% NaCl+mannitol 15%. Evaluation of cerebral hemodynamic (indexes of cerebral blood flow) was performed using doppler ultrasound of cerebral arteries. Results: The dynamics of specific volume velocity of blood flow per 100 grams of brain substance indicates that in the group of 0.9% NaCl and 0.9% NaCl+mannitol is the tendency to decrease the blood flow of the brain during 7 days of treatment, respectively: 2.8% and 7.5%. In patients with HES 130 solution cerebral blood flow increases by 14.2%, whereas when applied HAES-LX-5% during 7 days, it increases by 43.2% (p=0.004). Conclusions: The analysis of the data of treatment the patients with AIS showed the best effect (p=0.004) of improvement of the cerebral circulation in the use of the polyfunctional infusion solution HAES-LX-5% unlike the 0.9% NaCl group and group of 0.9% NaCl+mannitol where was a decrease of the dynamics of cerebral blood flow, which could lead to hypoperfusion of the brain.

Abstract W P209: Development of a Useful Brain Ischemic Stroke Model via a Transient Occlusion of Middle Cerebral Artery in the Nonhuman Primate

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Eiketsu Sho ◽  
Zhenghua Zhu ◽  
Yuchao Zhao ◽  
Jiqiao Chen ◽  
Daomei He ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Nonhuman Primate ◽  
Stroke Model ◽  
Cynomolgus Monkeys ◽  
Stroke Research ◽  
Reperfusion Period ◽  
The Brain

Objectives: Most experimental stroke research is carried out in rodents, but given differences between rodents and human, the nonhuman primate (NHP) models may provide a valuable tool to study the clinical therapy. We developed a surgical method for transient occlusion of the middle cerebral artery (MCA-M1) in the Cynomolgus monkeys to evaluate the MCA territory blood flow, the model stability, animal clinical neurological behavior, morphology changes under magnetic resonance imaging (MRI) and histopathology. Methods: The left brain sylvian fissure was exposed by a small fronto-temporal craniotomy. The MCA-M1 was exposed by microsurgical dissection and clipped for 4 hours. The brain blood flow was measured in the MCA territory during the ischemia period and early phase of reperfusion period. The clinical neurological examinations and MRI were carried out at regular post-operative course till 4 weeks of stroke. Results: During MCA occlusion, the MCA territory blood flow was decreased significantly in 80%. This territory was reflowed right after reperfusion and showed an overload in about 20% over pre ischemia flow within 1hr after reperfusion and gradually returned to previous flow (Fig 1). Animal neurological behavior changed significantly within 1 week and became a steady status of neurological impairment. MRI demonstrated extensive MCA territory infarction. Histologically, at the end of 4 week stroke the brain showed a clear board of glia proliferation between infarct and normal brain tissue. Conclusion: These results indicate a stable ischemic stroke model in cynomolgus monkeys after complete MCA-M1 occlusion, which will be a useful NHP stroke model for stroke research and the clinical therapeutic studies. Fig 1 Changes in MCA territory blood flow during ischemia-reperfusion period

scholarly journals Intranasal Salvinorin A Improves Long-term Neurological Function via Immunomodulation in a Mouse Ischemic Stroke Model

2021 ◽  
Author(s):  
Dilidaer Misilimu ◽  
Wei Li ◽  
Di Chen ◽  
Pengju Wei ◽  
Yichen Huang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Immune Cells ◽  
Intranasal Administration ◽  
Neurological Function ◽  
Salvinorin A ◽  
Stroke Model ◽  
Peripheral Immune Cells ◽  
The Brain

AbstractSalvinorin A (SA), a highly selective kappa opioid receptor agonist, has been shown to reduce brain infarct volume and improve neurological function after ischemic stroke. However, the underlying mechanisms have not been fully understood yet. Therefore, we explored whether SA provides neuroprotective effects by regulating the immune response after ischemic stroke both in the central nervous system (CNS) and peripheral circulation. In this study, adult male mice were subjected to transient Middle Cerebral Artery Occlusion (tMCAO) and then were treated intranasally with SA (50 μg/kg) or with the vehicle dimethyl sulfoxide (DMSO). Multiple behavioral tests were used to evaluate neurofunction. Flow cytometry and immunofluorescence staining were used to evaluate the infiltration of peripheral immune cells into the brain. The tracer cadaverine and endogenous immunoglobulin G (IgG) extravasation were used to detect blood brain barrier leakage. We observed that SA intranasal administration after ischemic stroke decreased the expression of pro-inflammatory factors in the brain. SA promoted the polarization of microglia/macrophages into a transitional phenotype and decreased the pro-inflammatory phenotype in the brain after tMCAO. Interestingly, SA treatment scarcely altered the number of peripheral immune cells but decreased the macrophage and neutrophil infiltration into the brain at 24 h after tMCAO. Furthermore, SA treatment also preserved BBB integrity, reduced long-term brain atrophy and white matter injury, as well as improved the long-term neurofunctional outcome in mice. In this study, intranasal administration of SA improved long-term neurological function via immuno-modulation and by preserving blood–brain barrier integrity in a mouse ischemic stroke model, suggesting that SA could potentially serve as an alternative treatment strategy for ischemic stroke. Graphic Abstract

Abstract 1122‐000181: Collateral Circulation in Ischemic Stroke is Not Determined by Anatomical Variants of the Cerebral Arteries

2021 ◽  
Vol 1 (S1) ◽  
Author(s):  
Karolina Brzegowy ◽  
Bernard Solewski ◽  
Paweł Brzegowy ◽  
Agata Musiał ◽  
Tadeusz Popiela ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Collateral Circulation ◽  
Cerebral Arteries ◽  
Anatomical Variations ◽  
Detailed Knowledge ◽  
Collateral Blood Flow ◽  
Posterior Portion ◽  
Cortical Vein ◽  
Anatomical Variants

Introduction : In acute ischemic stroke, collateral circulation determines tissue fate and treatment results. The aim of this study was to evaluate the role of anatomical variations of the Circle of Willis (CoW) in formation of cerebral collateral blood flow in patients with acute M1 occlusion. Methods : This study was a retrospective assessment of radiological examinations of patients with stroke due to middle cerebral artery M1 segment occlusion. All patients underwent mechanical thrombectomy from January 2015 until March 2021. The anatomy of the CoW was assessed on initial CT‐angiography and DSA. CTA was utilized to grade cranial collateral vasculature status and cortical vein opacification score (COVES). Non‐contrast CT scans and ASPECTS scores (using RAPID software) were used to determine the ischemic area. Results : A total of 100 patients were included in the analysis (58 females and 42 males, mean age: 71.6 +/‐ 13.9). We classified the anatomy of the CoW according to its continuity as a full circle. Patients with fully continuous CoW (n = 19) had worse COVES scores than those with CoW incomplete at both anterior and posterior portion (n = 9) (89% vs 68% with COVES 0–2, p = 0.179). No statistically significant results were found when comparing the enhancement of collaterals between these two groups (p = 0.390). The COVES scores were similar for patients with complete and incomplete anterior portions of CoW (77% vs 80% with COVES 0–2, p = 0.812). Patients with incomplete posterior portions of CoW had lower COVES scores than those with complete (80% vs 67% with COVES 0–2, p = 0.206). No statistically significant differences were discovered when comparing different types of the posterior communicating artery (adult, transitional and fetal). Analysis of ischemic areas determined as ASPECTS scores pre‐ and post‐thrombectomy yielded no significant differences between any of the groups. Conclusions : Although certain variants of the CoW have been reported to increase the risk of ischemic stroke, our results show that the anatomy of CoW has no large effect on collateral blood flow during acute M1 occlusion. We presume that the greater role is played by pial arterioles than anatomical variants of major cerebral arteries in cerebral collateral circulation formation. Detailed knowledge about the factors that influence collateral blood flow is crucial as it may aid in identification of patients prone to worse outcomes of ischemic stroke. Anatomical variants of CoW do not play a major role in formation of cerebral collaterals.

A computational model for blood perfusion in ischemic strokes

2020 ◽  
Vol 31 (05) ◽  
pp. 2050064
Author(s):  
Lanhua Zhang ◽  
Tao Wang ◽  
Mingfeng Yang ◽  
Shaowei Xue ◽  
Yujuan Li ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Computational Model ◽  
Correlation Matrix ◽  
Network Modeling ◽  
Small World ◽  
Blood Perfusion ◽  
And Topology ◽  
Vessel Injury ◽  
The Brain

Quantitative analysis is vital for blood perfusion in ischemic stroke validating and predicting blood trend to refer and remedy on selection, operation and intervention. We leveraged the complex network modeling blood perfusion to pursue the changes and trends of blood flow in ischemic stroke. According to conversion of the flow chart from laser Doppler perfusion images of rats into the correlation matrix, the blood perfusion networks were formed and topology characters were quantitatively analyzed. The results verified the steal phenomenon and the compensatory ability in the vessel injury in accord with clinical indexes by the basic characters and efficiency, especially the interesting local efficiency. In addition, the outcomes exhibited consistently the small-world characters in the brain of rats. This computational model strengthened the new way of blood perfusion and potential predictions for stroke’s assessment, operation and prevention from the basic vascular dynamic indexes and complex networks.

Neutrophil affinity for PGP and HAIYPRH (T7) peptide dual-ligand functionalized nanoformulation enhances the brain delivery of tanshinone IIA and exerts neuroprotective effects against ischemic stroke by inhibiting proinflammatory signaling pathways

2018 ◽  
Vol 42 (23) ◽  
pp. 19043-19061
Author(s):  
Yutao Li ◽  
Chiying An ◽  
Danan Han ◽  
Yanxin Dang ◽  
Xin Liu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Physicochemical Properties ◽  
Signaling Pathways ◽  
Blood Brain Barrier ◽  
Tanshinone Iia ◽  
Brain Barrier ◽  
Brain Delivery ◽  
Neuroprotective Effects ◽  
The Poor ◽  
The Brain

A great challenge to the therapy of ischemic stroke is the poor physicochemical properties and inability of the drug to cross the blood–brain barrier (BBB).

scholarly journals Ischemic stroke following abuse of Marijuana in a Nigerian adult male

2014 ◽  
Vol 05 (04) ◽  
pp. 417-419 ◽  
Author(s):  
Olalekan Oyinloye ◽  
Donald Nzeh ◽  
Ayodeji Yusuf ◽  
Emmanuel Sanya
Keyword(s):  
Young Adults ◽  
Ischemic Stroke ◽  
Basal Ganglia ◽  
Illicit Drugs ◽  
Cerebral Arteries ◽  
Cannabis Abuse ◽  
The Past ◽  
Middle Cerebral Arteries ◽  
Stroke In The Young ◽  
The Brain

ABSTRACTCannabis is the most widely used illicit drug among adolescents and young adults. Despite its widespread use, only a few reports exist on the association of cannabis use and stroke. A 26-year-old Nigerian male, developed right-sided ischemic stroke few hours after smoking three wraps of cannabis. He had smoked cannabis consistently for the past 4 years prior to the development of the stroke. Known stroke etiology and abuse of other illicit drugs were ruled out from history and investigations. Neuroimaging studies of the brain revealed infarcts in basal ganglia secondary to occlusion of blood flow in the left anterior and middle cerebral arteries. The mechanism of stroke in this patient was thought to be a cannabis-induced vasculopathy. Many cases of stroke in the young are increasingly being seen in hospitals in resource scarce countries. There seems to be a predilection for the basal ganglia in ischemic stroke following cannabis abuse. Therefore, cannabis abuse should be considered in young adults with basal ganglia infarcts, after excluding other known etiologies.

scholarly journals HEMODYNAMIC AND BIOELECTRICAL PROPERTIES OF THE BRAIN IN YOUNGER ADULTS WITH NONSTABLE BLOOD PRESSURE

2014 ◽  
Vol 13 (2) ◽  
pp. 12-17
Author(s):  
G. G. Efremushkin ◽  
T. V. Filippova ◽  
A. G. Kharlova ◽  
V. V. Dekhar
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Flow Velocity ◽  
Blood Flow Velocity ◽  
Cerebral Arteries ◽  
Bioelectrical Activity ◽  
Younger Adults ◽  
Flow Energy ◽  
Blood Filling ◽  
The Brain

Aim.To study macro- and microhemodynamics and bioelectrical properties of the brain in younger adults with nonstable blood pressure (BP).Material and methods.A population of 79 adults at the age of 19–24 (average 19,9±0,9 years) was examined. According to the BP level they were divided into two groups: 1–46 (58,5%) with stable normal BP (SNBP), and 2–33 (41,5%) with high normal BP inside the range for 1stlevel arterial hypertension, whose BP was not stable (UsBP), but changing from normal values to 1st level hypertension. All patients undergone investigation of brachiocephal and intracerebral vessels with blood flow velocity measurement along the vessel direction, the blood sectional volumetric flow and specific kinetic energy. Microcirculation in the brain was measured by rheoencephalography including parameters of the velocity, time and volumetric parameters. Bioelectricity studied by electroencephalography.Results.In patients with UsBP we found the increase of blood flow velocity, blood volume and specific kinetic flow energy in vertebral and general carotid arteries as in basilar and middle cerebral arteries to. In the area of microcirculation in patients with UsBP the blood filling of frontal lobes was decreased comparing to SNBP patients in whom blood filling showed “mosaic” pattern. In UsBP patients we found changes of bioelectrical activity which are related to the functioning of cortical and subcortical portions of the brain.Conclusion.In younger patients with UsBP there is developed discirculatory encephalopathy with damage of cortex and subcortical portions of the brain due to impaired hemodynamic and microcirculation.

scholarly journals Analysis of Thrombi Retrieved from Cerebral Arteries of Patients with Acute Ischemic Stroke.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 263-263
Author(s):  
Victor J. Marder ◽  
Dennis J. Chute ◽  
Sidney Starkman ◽  
Anna M. Abolian ◽  
Chelsea Kidwell ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Carotid Artery ◽  
Middle Cerebral Artery ◽  
Acute Ischemic Stroke ◽  
Cerebral Artery ◽  
Cerebral Arteries ◽  
Clinical Consequence ◽  
Initiation Of Therapy ◽  
Stroke Center

Abstract To obtain insights into the pathogenesis of ischemic stroke, we analyzed thromboemboli and other occlusive material retrieved acutely from the cerebral arteries of patients. The experimental design was an observational study in 25 consecutive patients with acute ischemic stroke treated by endovascular mechanical thromboembolectomy. Patients with acute occlusion of a proximal cerebral artery, a disabling neurologic deficit, and either initiation of therapy within 8 hours of onset or initiation of therapy beyond 8 hours if imaging demonstrated substantial residual penumbral tissue at risk were treated at a tertiary Comprehensive Stroke Center (the UCLA Stroke Center). Thrombus was removed by an endovascular mechanical embolectomy device (Merci® Retriever System, Concentric Medical, Mountain View, CA) after placement by angiographic catheter into the occluded intracranial carotid artery, middle cerebral artery or vertebral-basilar artery under fluoroscopic guidance. Our results show that the large majority (20 of 25) of extracted thrombi have similar histologic architecture, a complex of layered, sometimes serpentine, lengths of fibrin:platelet deposits interspersed with linear streaks of nucleated cells. This histology was prevalent with both cardioembolic and atherosclerotic etiologies, indicating the same pathogenetic influences of blood flow and shear in thrombus formation. This histologic pattern among thrombi was present in both the internal carotid artery (ICA) and the middle cerebral artery (MCA). Clots composed uniformly of erythrocytes were uncommon (3 of 25) and were observed only with incomplete extractions, suggesting that sampling was of the proximal thrombus tail where post-occlusion thrombosis had occurred under conditions of stagnant flow. Calcifications or cholesterol were not present. Thrombus size, not histology, predicted the site of arterial occlusion, with no thrombus larger than 3 mm width causing stroke limited to the MCA and no thrombus larger than 5 mm width removed from the ICA. Fungus-containing thrombus was extracted from one patient who had mycotic valvular disease, and an unusual complication occurred in another case, namely, scraping of a small atheroma and attached intima from the MCA, albeit without clinical consequence. We conclude that thromboemboli that cause acute ischemic stroke are of similar, complex structure, regardless of macroscopic dimensions, and are similarly influenced by blood flow, whether the primary etiology is cardioembolic or atherosclerotic. Embolus size is the critical aspect that determines its ultimate destination, those of more than 5 mm width appearing to bypass the cerebral vessels entirely. The mixed fibrin:platelet pattern present in the preponderance of thromboemboli provides foundation for the success of both antiplatelet and anticoagulant treatment strategies in stroke prevention.

scholarly journals Evolutionary Role of Epigenetics in Ischemic Stroke: A Review

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 1616-1620
Author(s):  
Rohini Agrawal ◽  
Prashant Amale ◽  
Shilpa Deshpande ◽  
Manish Deshmukh ◽  
Priti Bhoyar ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Hemorrhagic Stroke ◽  
Neural Stem Progenitor Cells ◽  
Genetic Level ◽  
Flow Through ◽  
After Cancer ◽  
The Brain ◽  
Global Population

Stroke is a Central Nervous System (CNS) disorder which occurs due to the obstruction in the brain blood flow. Stroke is mainly of two types, such as ischemic and hemorrhagic stroke. Ischemic stroke (80%) caused due to obstruction of blood flow through Middle Cerebral Artery (MCA) and characterized by a decreased supply of oxygen and glucose to CNS. In comparison, Hemorrhagic stroke (20%) mainly occurs due to the rupturing of blood vessels. Epidemiologically, it is the common reason of death after cancer and affecting millions of global population. There are many risk factors such as hypertension; hypercholesterolemia etc. which can exaggerate the condition of stroke. Various conventional therapies like Antiplatelets, Thrombolytic are available, but, there is a need to obtain a therapeutic approach that can provide prevention as well as a cure for the stroke. So the present review is primarily focused on epigenetic approach for ischemic stroke by Endogenous Transplantation of Neural Stem/Progenitor Cells (NSPCs). This, in turn, will decrease the level of REST protein at the genetic level and enhance the activity of Na+-Ca+ exchanger activity and lowers the excitotoxicity.

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