Targeting the gasdermin D as a strategy for ischemic stroke therapy

2021 ◽  
Vol 188 ◽  
pp. 114585
Author(s):  
Jiabing Wang ◽  
Jiali Yao ◽  
Yugang Liu ◽  
Lili Huang
Keyword(s):  
Ischemic Stroke ◽  
Stroke Therapy

scholarly journals Nanoparticle Delivered Anti-miR-141-3p for Stroke Therapy

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1011
Author(s):  
Karishma Dhuri ◽  
Rutesh N. Vyas ◽  
Leslie Blumenfeld ◽  
Rajkumar Verma ◽  
Raman Bahal
Keyword(s):  
Ischemic Stroke ◽  
Nucleic Acid ◽  
Double Emulsion ◽  
Artery Occlusion ◽  
Brain Parenchyma ◽  
Confocal Imaging ◽  
In Vivo Studies ◽  
Stroke Therapy ◽  
Systemic Delivery

Ischemic stroke and factors modifying ischemic stroke responses, such as social isolation, contribute to long-term disability worldwide. Several studies demonstrated that the aberrant levels of microRNAs contribute to ischemic stroke injury. In prior studies, we established that miR-141-3p increases after ischemic stroke and post-stroke isolation. Herein, we explored two different anti-miR oligonucleotides; peptide nucleic acid (PNAs) and phosphorothioates (PS) for ischemic stroke therapy. We used US FDA approved biocompatible poly (lactic-co-glycolic acid) (PLGA)-based nanoparticle formulations for delivery. The PNA and PS anti-miRs were encapsulated in PLGA nanoparticles by double emulsion solvent evaporation technique. All the formulated nanoparticles showed uniform morphology, size, distribution, and surface charge density. Nanoparticles also exhibited a controlled nucleic acid release profile for 48 h. Further, we performed in vivo studies in the mouse model of ischemic stroke. Ischemic stroke was induced by transient (60 min) occlusion of middle cerebral artery occlusion followed by a reperfusion for 48 or 72 h. We assessed the blood-brain barrier permeability of PLGA NPs containing fluorophore (TAMRA) anti-miR probe after systemic delivery. Confocal imaging shows uptake of fluorophore tagged anti-miR in the brain parenchyma. Next, we evaluated the therapeutic efficacy after systemic delivery of nanoparticles containing PNA and PS anti-miR-141-3p in mice after stroke. Post-treatment differentially reduced both miR-141-3p levels in brain tissue and infarct injury. We noted PNA-based anti-miR showed superior efficacy compared to PS-based anti-miR. Herein, we successfully established that nanoparticles encapsulating PNA or PS-based anti-miRs-141-3p probes could be used as a potential treatment for ischemic stroke.

Abstract 3268: Ct Perfusion As A Tool To Predict The Risk Of Hemorrhagic Transformation In Ischemic Stroke Treated With Tissue Plasminogen Activator: A Single Center Experience.

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Tareq Kass-Hout ◽  
Maxim Mokin ◽  
Omar Kass-Hout ◽  
Emad Nourollahzadeh ◽  
David Wack ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Stroke ◽  
Brain Tissue ◽  
Cerebral Blood Volume ◽  
Ct Perfusion ◽  
Intravenous Thrombolysis ◽  
Hemorrhagic Transformation ◽  
Stroke Therapy ◽  
Two Phase ◽  
The Mean

Objective: To use the Computed Tomography Perfusion (CTP) parameters at the time of hospital admission, including Cerebral Blood Volume (CBV) and Permeability Surface area product (PS), to identify patients with higher risk to develop hemorrhagic transformation in the setting of acute stroke therapy with intravenous thrombolysis. Methods: Retrospective study that compared admission CTP variables between patients with Hemorrhagic Transformation (HT) acute stroke and those with no hemorrhagic transformation. Both groups received standard of care intravenous thrombolysis with tPA. Twenty patients presented to our stroke center between the years 2007 - 2011 within 3 hours after stroke symptoms onset. All patients underwent two-phase 320 slice CTP which creates CBV and PS measurements. Patients were divided into two groups according to whether or not they had HT on a follow up CT head without contrast, done within 36 hours of the thrombolysis therapy. Clinical, demographic and CTP variables were compared between the HT and non-HT groups using logistic regression analyses. Results: HT developed in 8 (40%) patients. Patients with HT had lower ASPECT score ( P =.03), higher NIHSS on admission ( P= .01) and worse outcome ( P= .04) compared to patients who did not develop HT. Baseline blood flow defects were comparable between the two groups. The mean PS for the HT group was 0.53 mL/min/100g brain tissue, which was significantly higher than that for the non-HT group of 0.04 mL/min/100g brain tissue ( P <.0001). The mean area under the curve was 0.92 (95% CI). The PS threshold of 0.26 mL/min/100g brain tissue had a sensitivity of 80% and a specificity of 92% for detecting patients with high risk of hemorrhagic transformation after intravenous thrombolysis. Conclusions: Admission CTP measurements might be useful to predict patients who are at higher risk to develop hemorrhagic transformation after acute ischemic stroke therapy.

scholarly journals The Penumbra system for mechanical thrombectomy in endovascular acute ischemic stroke therapy

Neurology ◽  
2012 ◽  
Vol 79 (Issue 13, Supplement 1) ◽  
pp. S135-S141 ◽  
Author(s):  
S. I. Hussain ◽  
O. O. Zaidat ◽  
B.-F. M. Fitzsimmons
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Mechanical Thrombectomy ◽  
Stroke Therapy

scholarly journals Merci mechanical thrombectomy retriever for acute ischemic stroke therapy: Literature review

Neurology ◽  
2012 ◽  
Vol 79 (Issue 13, Supplement 1) ◽  
pp. S126-S134 ◽  
Author(s):  
A. Alshekhlee ◽  
D. J. Pandya ◽  
J. English ◽  
O. O. Zaidat ◽  
N. Mueller ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Literature Review ◽  
Acute Ischemic Stroke ◽  
Mechanical Thrombectomy ◽  
Stroke Therapy

Abstract TP24: Trends in Iv r-tpa and Thrombectomy Treatment Rates Before and After the LVO RCT’s in a Regional Tele-stroke Network

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Naregnia Pierre Louis ◽  
Suman Nalluri ◽  
Benny Kim ◽  
Aashish Anand ◽  
Tanzila Shams ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ischemic Stroke ◽  
Mechanical Thrombectomy ◽  
Statistical Test ◽  
Stroke Therapy ◽  
Stroke Patients ◽  
Chi Square ◽  
The Third ◽  
Before And After ◽  
Acute Stroke Therapy

The presentation of endovascular stroke trials at international stroke conference was a land mark event in acute stroke therapy. This study aims to analyze the rates of utilization of IV r-tPA, with or without mechanical thrombectomy before and after the 2015 International Stroke Conference (ISC) in a large regional tele-stroke network. Methods: A systematic review of prospective telestroke and procedure database was performed for 18 months prior and 18 months post conference. There were three groups included in the analysis. The first group consisted ischemic stroke patients presented within 12 hours of onset including inpatient events, transfers from primary centers and rural clinics. The second group consisted of patients who received IV r-tPA, and the third group consisted of patients who received IV r-tPA and/or underwent mechanical thrombectomy for a demonstrated LVO. Results: A total of 2628 consecutive ischemic stroke events presented within 12 hours of onset were evaluated. In the pre-ISC conference group, there were 1135 ischemic stroke patients. IV r-tPA was given 535 times(47.1%) and mechanical thrombectomy was utilized in addition to IV r-tPA or alone 42 times(3.7%). In the post-ISC conference group, there were 1493 ischemic stroke patients. IV r-tPA was given 642 times(43%) and mechanical thrombectomy was utilized in addition to IV r-tPA or alone 132 times(8.84%). The Chi Square statistical test was performed comparing these groups. When comparing the rate of IV r-tPA usage, there was a significant decrease from the pre-ISC conference group to the post-ISC conference group (P= 0.04). When comparing the rate of mechanical thrombectomy performed, there was a significant increase of greater than double the percentage of thrombectomy procedures performed in the post conference group compared to the preconference group (p< 0.001). Conclusion: There was a significant decrease in IV r-tPA usage but a greater than double the increase in the thrombectomy rate . This may be secondary to increased awareness of benefit of thrombectomy at referral centers. Slightly lower rates of IV r-tPA usage may be secondary to an increase in transfers of patients outside of the 0-4.5 hr window but were deemed candidates for thrombectomy.

Notch3 Mutation Detection in Stroke Patients and Selective Nanoliposome in Stroke Alleviation in a Mouse Model

2021 ◽  
Vol 17 (9) ◽  
pp. 1735-1744
Author(s):  
Yanxia Wang ◽  
Xinmeng Li ◽  
Ying Liu ◽  
Wenjing Guo ◽  
Jiangpo Chen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Mouse Model ◽  
Control Group ◽  
Stroke Therapy ◽  
Stroke Patients ◽  
Brain Vessels ◽  
Stroke Treatment ◽  
Pathological Alteration ◽  
Notch3 Mutation ◽  
Long Term Prognosis

This study analyzed the correlation between the Notch3 mutation and stroke by testing an effective nanoparticle-loaded aspirin in stroke therapy. Fifty patients with ischemic stroke were followed for two years, and fifty healthy persons served as the control group. By RT-PCR, this study revealed that the Notch3 mutation existed in ischemic stroke patients who were more likely to have a family history, small vessel lesions, relatively frequent cerebral hemorrhage, and poor long-term prognosis. Liposome-aspirin-chitosan nanoparticle (LACN) was constructed as a nano-composite for stroke treatment. Notch3 Arg170Cys knock-in mice were prepared as a mutant Notch3 mouse model to test the LACN infiltration efficiency and observe the anti-stroke capacity. We found that LACN could better transport aspirin into brain vessels than the Polyethyleneimine (PEI) delivery system. However, in the Notch3 mutation mouse model, cerebral infarction and hemorrhage often occurred after being treated with aspirin. Still, LACN better prolongs the half-life of aspirin, rescues the pathological alteration of stroke in the brain, and reduces inflammatory reaction and oxidative stress response. In conclusion, the Notch3 mutation is closely related to stroke occurrence, and LACN may be a better choice for stroke therapy in the future.

scholarly journals Histological stroke clot analysis after thrombectomy: Technical aspects and recommendations

2019 ◽  
Vol 15 (5) ◽  
pp. 467-476 ◽  
Author(s):  
S Staessens ◽  
S Fitzgerald ◽  
T Andersson ◽  
F Clarençon ◽  
F Denorme ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Endovascular Procedures ◽  
Cerebral Arteries ◽  
Research Field ◽  
Stroke Therapy ◽  
Technical Aspects ◽  
Stroke Research

The recent advent of endovascular procedures has created the unique opportunity to collect and analyze thrombi removed from cerebral arteries, instigating a novel subfield in stroke research. Insights into thrombus characteristics and composition could play an important role in ongoing efforts to improve acute ischemic stroke therapy. An increasing number of centers are collecting stroke thrombi. This paper aims at providing guiding information on thrombus handling, procedures, and analysis in order to facilitate and standardize this emerging research field.

Ultrasound controlled anti‐inflammatory polarization of platelet decorated microglia for targeted ischemic stroke therapy

2020 ◽  
Author(s):  
Jinghong Li ◽  
Yujie Li ◽  
Xucong Teng ◽  
Chunrong Yang ◽  
Yongji Wang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Stroke Therapy ◽  
Anti Inflammatory

scholarly journals Lessons from Recent Advances in Ischemic Stroke Management and Targeting Kv2.1 for Neuroprotection

2020 ◽  
Vol 21 (17) ◽  
pp. 6107 ◽  
Author(s):  
Chung-Yang Yeh ◽  
Anthony J. Schulien ◽  
Bradley J. Molyneaux ◽  
Elias Aizenman
Keyword(s):  
Ischemic Stroke ◽  
Time Window ◽  
Stroke Therapy ◽  
Stroke Management ◽  
Preclinical Research ◽  
Endovascular Thrombectomy ◽  
Stroke Treatment ◽  
Cell Death Pathway ◽  
To Receive ◽  
Neuroprotective Therapies

Achieving neuroprotection in ischemic stroke patients has been a multidecade medical challenge. Numerous clinical trials were discontinued in futility and many were terminated in response to deleterious treatment effects. Recently, however, several positive reports have generated the much-needed excitement surrounding stroke therapy. In this review, we describe the clinical studies that significantly expanded the time window of eligibility for patients to receive mechanical endovascular thrombectomy. We further summarize the results available thus far for nerinetide, a promising neuroprotective agent for stroke treatment. Lastly, we reflect upon aspects of these impactful trials in our own studies targeting the Kv2.1-mediated cell death pathway in neurons for neuroprotection. We argue that recent changes in the clinical landscape should be adapted by preclinical research in order to continue progressing toward the development of efficacious neuroprotective therapies for ischemic stroke.

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