An Angiopep-2 functionalized nanoformulation enhances brain accumulation of tanshinone IIA and exerts neuroprotective effects against ischemic stroke

2018 ◽  
Vol 42 (21) ◽  
pp. 17359-17370 ◽  
Author(s):  
Yutao Li ◽  
Yanxin Dang ◽  
Dandan Han ◽  
Yong Tan ◽  
Xin Liu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Tanshinone Iia ◽  
Effective Intervention ◽  
Neuroprotective Effects ◽  
Neuroprotective Drugs ◽  
The Brain

Effective intervention against ischemic stroke requires delivery of potent neuroprotective drugs to the brain.

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).

Neuroprotection via AT2 receptor agonists in ischemic stroke

2018 ◽  
Vol 132 (10) ◽  
pp. 1055-1067 ◽  
Author(s):  
Douglas M. Bennion ◽  
U. Muscha Steckelings ◽  
Colin Sumners
Keyword(s):  
Ischemic Stroke ◽  
Neuronal Damage ◽  
Recombinant Tissue Plasminogen Activator ◽  
Neurological Deficits ◽  
At2 Receptor ◽  
Neuroprotective Effects ◽  
Receptor Agonists ◽  
Stroke Epidemiology ◽  
The Brain

Stroke is a devastating disease that afflicts millions of people each year worldwide. Ischemic stroke, which accounts for ~88% of cases, occurs when blood supply to the brain is decreased, often because of thromboembolism or atherosclerotic occlusion. This deprives the brain of oxygen and nutrients, causing immediate, irreversible necrosis within the core of the ischemic area, but more delayed and potentially reversible neuronal damage in the surrounding brain tissue, the penumbra. The only currently approved therapies for ischemic stroke, the thrombolytic agent recombinant tissue plasminogen activator (rtPA) and the endovascular clot retrieval/destruction processes, are aimed at restoring blood flow to the infarcted area, but are only available for a minority of patients and are not able in most cases to completely restore neurological deficits. Consequently, there remains a need for agents that will protect neurones against death following ischemic stroke. Here, we evaluate angiotensin II (Ang II) type 2 (AT2) receptor agonists as a possible therapeutic target for this disease. We first provide an overview of stroke epidemiology, pathophysiology, and currently approved therapies. We next review the large amount of preclinical evidence, accumulated over the past decade and a half, which indicates that AT2 receptor agonists exert significant neuroprotective effects in various animal models, and discuss the potential mechanisms involved. Finally, after discussing the challenges of delivering blood–brain barrier (BBB) impermeable AT2 receptor agonists to the infarcted areas of the brain, we summarize the evidence for and against the development of these agents as a promising therapeutic strategy for ischemic stroke.

scholarly journals New Approaches in Nanomedicine for Ischemic Stroke

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 757
Author(s):  
Clara Correa-Paz ◽  
Andrés da Silva-Candal ◽  
Ester Polo ◽  
Jérôme Parcq ◽  
Denis Vivien ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Neurological Diseases ◽  
Drug Carriers ◽  
Developed Countries ◽  
Therapeutic Window ◽  
Promising Tool ◽  
Neuroprotective Drugs ◽  
Recovery Strategies ◽  
Patient’S Outcome ◽  
The Brain

Ischemic stroke, caused by the interruption of blood flow to the brain and subsequent neuronal death, represents one of the main causes of disability in developed countries. Therapeutic methods such as recanalization approaches, neuroprotective drugs, or recovery strategies have been widely developed to improve the patient’s outcome; however, important limitations such as a narrow therapeutic window, the ability to reach brain targets, or drug side effects constitute some of the main aspects that limit the clinical applicability of the current treatments. Nanotechnology has emerged as a promising tool to overcome many of these drug limitations and improve the efficacy of treatments for neurological diseases such as stroke. The use of nanoparticles as a contrast agent or as drug carriers to a specific target are some of the most common approaches developed in nanomedicine for stroke. Throughout this review, we have summarized our experience of using nanotechnology tools for the study of stroke and the search for novel therapies.

scholarly journals Neuroprotection by glutamate oxaloacetate transaminase in ischemic stroke: An experimental study

2011 ◽  
Vol 31 (6) ◽  
pp. 1378-1386 ◽  
Author(s):  
Francisco Campos ◽  
Tomás Sobrino ◽  
Pedro Ramos-Cabrer ◽  
Bárbara Argibay ◽  
Jesús Agulla ◽  
...  
Keyword(s):  
Animal Model ◽  
Ischemic Stroke ◽  
Arterial Occlusion ◽  
Brain Parenchyma ◽  
Resonance Spectroscopy ◽  
Glutamate Oxaloacetate Transaminase ◽  
Neuroprotective Effects ◽  
Sensorimotor Deficits ◽  
Cerebral Arterial Occlusion ◽  
The Brain

As ischemic stroke is associated with an excessive release of glutamate into the neuronal extracellular space, a decrease in blood glutamate levels could provide a mechanism to remove it from the brain tissue, by increasing the brain-blood gradient. In this regard, the ability of glutamate oxaloacetate transaminase (GOT) to metabolize glutamate in blood could represent a potential neuroprotective tool for ischemic stroke. This study aimed to determine the neuroprotective effects of GOT in an animal model of cerebral ischemia by means of a middle cerebral arterial occlusion (MCAO) following the Stroke Therapy Academic Industry Roundtable (STAIR) group guidelines. In this animal model, oxaloacetate-mediated GOT activation inhibited the increase of blood and cerebral glutamate after MCAO. This effect is reflected in a reduction of infarct size, smaller edema volume, and lower sensorimotor deficits with respect to controls. Magnetic resonance spectroscopy confirmed that the increase of glutamate levels in the brain parenchyma after MCAO is inhibited after oxaloacetate-mediated GOT activation. These findings show the capacity of the GOT to remove glutamate from the brain by means of blood glutamate degradation, and suggest the applicability of this enzyme as an efficient and novel neuroprotective tool against ischemic stroke.

Characterization of Ischemic Stroke in CT Images using Image Processing

2017 ◽  
Vol 7 (9) ◽  
pp. 18
Author(s):  
Amal Alzain ◽  
Suhaib Alameen ◽  
Rani Elmaki ◽  
Mohamed E. M. Gar-Elnabi
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Classification Accuracy ◽  
Ct Images ◽  
Gray Level ◽  
Level Variation ◽  
Interactive Data ◽  
The Brain ◽  
Brain Tissues

This study concern to characterize the brain tissues to ischemic stroke, gray matter, white matter and CSF using texture analysisto extract classification features from CT images. The First Order Statistic techniques included sevenfeatures. To find the gray level variation in CT images it complements the FOS features extracted from CT images withgray level in pixels and estimate the variation of thesubpatterns. analyzing the image with Interactive Data Language IDL software to measure the grey level of images. The results show that the Gray Level variation and   features give classification accuracy of ischemic stroke 97.6%, gray matter95.2%, white matter 97.3% and the CSF classification accuracy 98.0%. The overall classification accuracy of brain tissues 97.0%.These relationships are stored in a Texture Dictionary that can be later used to automatically annotate new CT images with the appropriate brain tissues names.

Heat Shock Protein 70 kDa as a Target for Diagnostics and Therapy of Cardiovascular and Cerebrovascular Diseases

2019 ◽  
Vol 25 (6) ◽  
pp. 710-714 ◽  
Author(s):  
Ekaterina V. Konstantinova ◽  
Natalia S. Chipigina ◽  
Marina H. Shurdumova ◽  
E.I. Kovalenko ◽  
Alexander M. Sapozhnikov
Keyword(s):  
Myocardial Infarction ◽  
Ischemic Stroke ◽  
Heat Shock ◽  
Cerebrovascular Diseases ◽  
Peripheral Blood Lymphocytes ◽  
Neuroprotective Effects ◽  
Adverse Conditions ◽  
Shock Proteins ◽  
Diagnostics And Therapy ◽  
Main Factor

Acute focal ischemia is a main factor of pathogenesis of a number of widespread cardiovascular and cerebrovascular diseases, in particular, myocardial infarction and ischemic stroke. It is known that under the conditions of ischemia expression of intracellular heat shock proteins (HSPs), especially HSP70, grows greatly irrespective of the cell type. This stress-induced cell response is connected with cytoprotective properties of HSP70. The protective functions of HSP70 contribute to the cell survival under adverse conditions and inhibit development of programmed cell death. It was shown, that the level of HSP70 increases in cardiomyocytes and brain cells in response to ischemia, that was connected with cardioprotective and neuroprotective effects. Besides, in recent years, clinical studies of HSP70 have demonstrated elevated level of HSP70 in peripheral blood lymphocytes in groups of patients with ischemic stroke and myocardial infarction. This review indicates that HSP70 can serve as a target for developing new approaches to diagnostics and therapy of cardiovascular and cerebrovascular diseases.

scholarly journals The Potential Effects of Phytoestrogens: The Role in Neuroprotection

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2954
Author(s):  
Justyna Gorzkiewicz ◽  
Grzegorz Bartosz ◽  
Izabela Sadowska-Bartosz
Keyword(s):  
Neuroprotective Effect ◽  
Antioxidant Properties ◽  
Estrogen Therapy ◽  
Neuroprotective Effects ◽  
Potential Health ◽  
Naturally Occurring ◽  
Epigenetic Effects ◽  
Estrogen Synthesis ◽  
Health Promoting ◽  
The Brain

Phytoestrogens are naturally occurring non-steroidal phenolic plant compounds. Their structure is similar to 17-β-estradiol, the main female sex hormone. This review offers a concise summary of the current literature on several potential health benefits of phytoestrogens, mainly their neuroprotective effect. Phytoestrogens lower the risk of menopausal symptoms and osteoporosis, as well as cardiovascular disease. They also reduce the risk of brain disease. The effects of phytoestrogens and their derivatives on cancer are mainly due to the inhibition of estrogen synthesis and metabolism, leading to antiangiogenic, antimetastatic, and epigenetic effects. The brain controls the secretion of estrogen (hypothalamus-pituitary-gonads axis). However, it has not been unequivocally established whether estrogen therapy has a neuroprotective effect on brain function. The neuroprotective effects of phytoestrogens seem to be related to both their antioxidant properties and interaction with the estrogen receptor. The possible effects of phytoestrogens on the thyroid cause some concern; nevertheless, generally, no serious side effects have been reported, and these compounds can be recommended as health-promoting food components or supplements.

scholarly journals Mesenchymal Stem Cell Derived Extracellular Vesicles for Repairing the Neurovascular Unit after Ischemic Stroke

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 767
Author(s):  
Courtney Davis ◽  
Sean I. Savitz ◽  
Nikunj Satani
Keyword(s):  
Ischemic Stroke ◽  
Extracellular Vesicles ◽  
Neurovascular Unit ◽  
Culture Conditions ◽  
Therapeutic Effects ◽  
Stroke Treatment ◽  
Inflammatory Molecules ◽  
The Brain

Ischemic stroke is a debilitating disease and one of the leading causes of long-term disability. During the early phase after ischemic stroke, the blood-brain barrier (BBB) exhibits increased permeability and disruption, leading to an influx of immune cells and inflammatory molecules that exacerbate the damage to the brain tissue. Mesenchymal stem cells have been investigated as a promising therapy to improve the recovery after ischemic stroke. The therapeutic effects imparted by MSCs are mostly paracrine. Recently, the role of extracellular vesicles released by these MSCs have been studied as possible carriers of information to the brain. This review focuses on the potential of MSC derived EVs to repair the components of the neurovascular unit (NVU) controlling the BBB, in order to promote overall recovery from stroke. Here, we review the techniques for increasing the effectiveness of MSC-based therapeutics, such as improved homing capabilities, bioengineering protein expression, modified culture conditions, and customizing the contents of EVs. Combining multiple techniques targeting NVU repair may provide the basis for improved future stroke treatment paradigms.

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