Gelatin nanoparticles enhance the neuroprotective effects of intranasally administered osteopontin in rat ischemic stroke model

While clinical trials have now solidified the role of thrombectomy in emergent large vessel occlusive stroke, additional therapies are needed to optimize patient outcome. Using our previously described experimental ischemic stroke model for evaluating adjunctive intra-arterial drug therapy after vessel recanalization, we studied the potential neuroprotective effects of verapamil. A calcium channel blocker, verapamil is often infused intra-arterially by neurointerventionalists to treat cerebral vasospasm. Such a direct route of administration allows for both focused targeting of stroke-impacted brain tissue and minimizes potential systemic side effects. Intra-arterial administration of verapamil at a flow rate of 2.5 µl/min and injection volume of 10 µl immediately after middle cerebral artery recanalization in C57/Bl6 mice was shown to be profoundly neuroprotective as compared to intra-arterial vehicle-treated stroke controls. Specifically, we noted a significant (P ≤ 0.05) decrease in infarct volume, astrogliosis, and cellular apoptosis as well as a significant increase in neuronal survival and functional outcome over seven days. Furthermore, intra-arterial administration of verapamil was well tolerated with no hemorrhage, systemic side effects, or increased mortality. Thus, verapamil administered intra-arterially immediately following recanalization in experimental ischemic stroke is both safe and neuroprotective and merits further study as a potential therapeutic adjunct to thrombectomy.

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Dietary Supplementation Exerts Neuroprotective Effects in Ischemic Stroke Model

Rejuvenation Research ◽

10.1089/rej.2007.0608 ◽

2008 ◽

Vol 11 (1) ◽

pp. 201-214 ◽

Cited By ~ 33

Author(s):

Takao Yasuhara ◽

Koichi Hara ◽

Mina Maki ◽

Tadashi Masuda ◽

Cyndy D. Sanberg ◽

...

Keyword(s):

Ischemic Stroke ◽

Dietary Supplementation ◽

Stroke Model ◽

Neuroprotective Effects

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

Current Pharmaceutical Design ◽

10.2174/1381612825666190329123924 ◽

2019 ◽

Vol 25 (6) ◽

pp. 710-714 ◽

Cited By ~ 2

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.

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Selective intra-carotid blood cooling in acute ischemic stroke: A safety and feasibility study in an ovine stroke model

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x211024952 ◽

2021 ◽

pp. 0271678X2110249

Author(s):

Giorgio FM Cattaneo ◽

Andrea M Herrmann ◽

Sebastian A Eiden ◽

Manuela Wieser ◽

Elias Kellner ◽

...

Keyword(s):

Ischemic Stroke ◽

Carotid Artery ◽

Acute Ischemic Stroke ◽

Neurological Outcome ◽

Artery Occlusion ◽

Control Group ◽

Stroke Model ◽

Primary Endpoints ◽

Neuroprotective Strategy ◽

Vessel Patency

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model. Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes. Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups. Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy.

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Development of a photochemical thrombosis investigation system to obtain a rabbit ischemic stroke model

Scientific Reports ◽

10.1038/s41598-021-85348-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yoonhee Kim ◽

Yoon Bum Lee ◽

Seung Kuk Bae ◽

Sung Suk Oh ◽

Jong-ryul Choi

Keyword(s):

Ischemic Stroke ◽

Brain Damage ◽

Rabbit Model ◽

Specific Area ◽

Brain Atlas ◽

Rabbit Brain ◽

Stroke Model ◽

Triphenyltetrazolium Chloride ◽

Induction System

AbstractPhotochemical thrombosis is a method for the induction of ischemic stroke in the cerebral cortex. It can generate localized ischemic infarcts in the desired region; therefore, it has been actively employed in establishing an ischemic stroke animal model and in vivo assays of diagnostic and therapeutic techniques for stroke. To establish a rabbit ischemic stroke model and overcome the shortcoming of previous studies that were difficult to build a standardized photothrombotic rabbit model, we developed a photochemical thrombosis induction system that can produce consistent brain damage on a specific area. To verify the generation of photothrombotic brain damage using the system, longitudinal magnetic resonance imaging, 2,3,5-triphenyltetrazolium chloride staining, and histological staining were applied. These analytical methods have a high correlation for ischemic infarction and are appropriate for analyzing photothrombotic brain damage in the rabbit brain. The results indicated that the photothrombosis induction system has a main advantage of being accurately controlled a targeted region of photothrombosis and can produce cerebral hemisphere lesions on the target region of the rabbit brain. In conjugation with brain atlas, it can induce photochemical ischemic stroke locally in the part of the brain that is responsible for a particular brain function and the system can be used to develop animal models with degraded specific functions. Also, the photochemical thrombosis induction system and a standardized rabbit ischemic stroke model that uses this system have the potential to be used for verifications of biomedical techniques for ischemic stroke at a preclinical stage in parallel with further performance improvements.

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O-BN002. Intravenous administration of poly(lactide-co-glycolide) nanoparticle encapsulating brain-derived neurotrophic factor promotes neuroprotection in an ischemic stroke model in the rat

Clinical Neurophysiology ◽

10.1016/j.clinph.2021.02.160 ◽

2021 ◽

Vol 132 (8) ◽

pp. e77-e78

Author(s):

Siti Norsyafika Kamarudin ◽

Igor Iezhitsa ◽

Minaketan Tripathy ◽

Renad Alyautdin ◽

Nafeeza Mohd Ismail

Keyword(s):

Ischemic Stroke ◽

Intravenous Administration ◽

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

Stroke Model

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The Effects ofChunghyul-Dan(A Korean Medicine Herbal Complex) on Cardiovascular and Cerebrovascular Diseases: A Narrative Review

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/2601740 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Woo-Sang Jung ◽

Seungwon Kwon ◽

Seung-Yeon Cho ◽

Seong-Uk Park ◽

Sang-Kwan Moon ◽

...

Keyword(s):

Ischemic Stroke ◽

Ethanol Extract ◽

Inhibitory Effect ◽

Cerebrovascular Diseases ◽

Stroke Recurrence ◽

Neuroprotective Effects ◽

Clinical Safety ◽

Endogenous Catecholamine ◽

Rhei Rhizoma ◽

Coa Reductase

Chunghyul-dan(CHD) is a herbal complex containing 80% ethanol extract and is composed ofScutellariae Radix,Coptidis Rhizoma,Phellodendri Cortex,Gardeniae Fructus, andRhei Rhizoma. We have published several experimental and clinical research articles on CHD. It has shown antilipidemic, antihypertensive, antiatherosclerotic, and inhibitory effects on ischemic stroke recurrence with clinical safety in the previous studies. The antilipidemic effect of CHD results from 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and pancreatic lipase-inhibitory activity. The antihypertensive effect likely results from the inhibitory effect on endogenous catecholamine(s) release and harmonization of all components showing the antihypertensive effects. Furthermore, anti-inflammatory and antioxidant effects on endothelial cells are implicated to dictate the antiatherosclerotic effects of CHD. It also showed neuroprotective effects on cerebrovascular and parkinsonian models. These effects of CHD could be helpful for the prevention of the recurrence of ischemic stroke. Therefore, we suggest that CHD could be a promising medication for treating and preventing cerebrovascular and cardiovascular diseases. However, to validate and better understand these findings, well-designed clinical studies are required.

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