Nanomedicinal Strategies as Emerging Therapeutic Avenues for the Management Cerebral Ischemia

2020 ◽  
Vol 19 ◽  
Author(s):  
Saman Fatima ◽  
Syed Naved Quadri ◽  
Shaheda Parveen ◽  
Sarwar Beg ◽  
Md Abul Barkat ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Health Risks ◽  
Global Scale ◽  
Preclinical Studies ◽  
Neuronal Regeneration ◽  
Stroke Patients ◽  
Mortality And Morbidity ◽  
The Brain

: Amongst the various diseases on global scale, the second leading cause of mortality and morbidity is ischemic stroke due to the unavailability of an effective therapy. With the growing occurrence and its related health risks along with the absence of effective therapeutics, the ischemic stroke demands the continued and intensive research to explore the effective and safe therapeutics. These therapies may positively affect the numerous pathways associated with neuroprotection thus, extending the advantages to a larger population of stroke patients. Several preclinical studies employing neuroprotectants have shown promising outcomes, but failed in clinical trials either because of the lack of safety or efficacy. The blood brain barrier (BBB) restricts delivery of various potent neuroprotectants to the specific areas of the brain. The application of nanovehicles for delivery of drugs in the brain however, could revolutionize the treatment of ischemic stroke. These nanovehicles loaded with the drug could readily traverse the BBB via carrier, receptor and adsorptive-mediated endocytosis into the brain without compromising the integrity of BBB. Recent advances in neuronanotherapeutics have resulted in the improved neuronal regeneration and recovery after the ischemic stroke. In this review, we have attempted to discuss unexploited neuronanotherapeutics potentials to treat and manage ischemic stroke.

Abstract TP274: Orosomucoid-1 Protein Increases Following Ischemic Stroke in the Brain and Periphery

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Hetal Mistry ◽  
Madeline Levy ◽  
Meaghan Roy-O'Reilly ◽  
Louise McCullough
Keyword(s):  
Sex Differences ◽  
Ischemic Stroke ◽  
Rna Sequencing ◽  
Multiple Testing ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Stroke Patients ◽  
Post Stroke ◽  
Protein Levels ◽  
The Brain

Background and Purpose: Orosomucoid-1 (ORM-1) is an abundant protein with important roles in inflammation and immunosuppression. We utilized RNA sequencing to measure mRNA levels in human ischemic stroke patients, with confirmation by serum ORM-1 protein measurements. A mouse model of ischemic stroke was then used to examine post-stroke changes in ORM-1 within the brain itself. Hypothesis: We tested the hypothesis that ORM-1 levels increase following ischemic stroke, with sex differences in protein dynamics over time. Methods: RNA sequencing was performed on whole blood from ischemic stroke patients (n=23) and controls (n=12), with Benjamini-Hochberg correction for multiple testing. Enzyme-linked immunosorbent assay was performed on serum from ischemic stroke patients (n=28) and controls (n=8), with analysis by T-test. For brain analysis, mice (n=14) were subjected to a 90-minute middle cerebral artery occlusion (MCAO) surgery and sacrificed 6 or 24 hours after stroke. Control mice underwent parallel “sham” surgery without occlusion. Western blotting was used to detect ORM-1 protein levels in whole brain, with analysis by two-way ANOVA. Results: RNA sequencing showed a 2.8-fold increase in human ORM-1 at 24 hours post-stroke (q=.0029), an increase also seen in serum ORM-1 protein levels (p=.011). Western blot analysis of mouse brain revealed that glycosylated (p=0.0003) and naive (p=0.0333) forms of ORM-1 were higher in female mice compared to males 6 hours post-stroke. Interestingly, ORM-1 levels were higher in the brains of stroke mice at 6 hours (p=.0483), while at 24 hours ORM-1 levels in stroke mice were lower than their sham counterparts (p=.0212). In both human and mouse data, no sex differences were seen in ORM-1 levels in the brain or periphery at 24 hours post-stroke. Conclusion: In conclusion, ORM-1 is a sexually dimorphic protein involved in the early (<24 hour) response to ischemic stroke. This research serves as an initial step in determining the mechanism of ORM-1 in the ischemic stroke response and its potential as a future therapeutic target for both sexes.

scholarly journals Comorbidity and age in the modelling of stroke: are we still failing to consider the characteristics of stroke patients?

2020 ◽  
Vol 4 (1) ◽  
pp. e100013 ◽  
Author(s):  
Sarah K McCann ◽  
Catherine B Lawrence
Keyword(s):  
Infarct Volume ◽  
Treatment Options ◽  
Response To Treatment ◽  
Experimental Stroke ◽  
Preclinical Studies ◽  
Stroke Patients ◽  
Mortality And Morbidity ◽  
Degree Of Protection ◽  
Stroke Research ◽  
Drug Interventions

Stroke is a significant cause of mortality and morbidity for which there are limited treatment options. Virtually all drug interventions that have been successful preclinically in experimental stroke have failed to translate to an effective treatment in the clinical setting. In this review, we examine one of the factors likely contributing to this lack of translation, the failure of preclinical studies to consider fully the advanced age and comorbidities (eg, hypertension or diabetes) present in most patients with stroke. Age and comorbidities affect the likelihood of suffering a stroke, disease progression and the response to treatment. Analysing data from preclinical systematic reviews of interventions for ischaemic stroke we show that only 11.4% of studies included an aged or comorbid model, with hypertension being the most frequent. The degree of protection (% reduction in infarct volume) varied depending on the comorbidity and the type of intervention. We consider reasons for the lack of attention to comorbid and aged animals in stroke research and discuss the value of testing a potential therapy in models representing a range of comorbidities that affect patients with stroke. These models can help establish any limits to a treatment’s efficacy and inform the design of clinical trials in appropriate patient populations.

scholarly journals Targeting α-Synuclein for PD Therapeutics: A Pursuit on All Fronts

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 391 ◽  
Author(s):  
Margaux Teil ◽  
Marie-Laure Arotcarena ◽  
Emilie Faggiani ◽  
Florent Laferriere ◽  
Erwan Bezard ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Clinical Trials ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Lewy Bodies ◽  
Curative Treatment ◽  
Preclinical Studies ◽  
Cytoplasmic Inclusions ◽  
The Many ◽  
The Brain

Parkinson’s Disease (PD) is characterized both by the loss of dopaminergic neurons in the substantia nigra and the presence of cytoplasmic inclusions called Lewy Bodies. These Lewy Bodies contain the aggregated α-synuclein (α-syn) protein, which has been shown to be able to propagate from cell to cell and throughout different regions in the brain. Due to its central role in the pathology and the lack of a curative treatment for PD, an increasing number of studies have aimed at targeting this protein for therapeutics. Here, we reviewed and discussed the many different approaches that have been studied to inhibit α-syn accumulation via direct and indirect targeting. These analyses have led to the generation of multiple clinical trials that are either completed or currently active. These clinical trials and the current preclinical studies must still face obstacles ahead, but give hope of finding a therapy for PD with time.

Acute Kidney Injury in Acute Ischemic Stroke Patients in Clinical Trials

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Adnan I. Qureshi ◽  
Hunain Aslam ◽  
Werdah Zafar ◽  
Wei Huang ◽  
Iryna Lobanova ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Clinical Trials ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Kidney Injury ◽  
Stroke Patients

scholarly journals Abnormal EEG Complexity and Functional Connectivity of Brain in Patients with Acute Thalamic Ischemic Stroke

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Shuang Liu ◽  
Jie Guo ◽  
Jiayuan Meng ◽  
Zhijun Wang ◽  
Yang Yao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Connectivity ◽  
Healthy Subjects ◽  
Brain Network ◽  
Control Group ◽  
Stroke Patients ◽  
Cerebral Disease ◽  
Essential Information ◽  
Stroke Group ◽  
The Brain

Ischemic thalamus stroke has become a serious cardiovascular and cerebral disease in recent years. To date the existing researches mostly concentrated on the power spectral density (PSD) in several frequency bands. In this paper, we investigated the nonlinear features of EEG and brain functional connectivity in patients with acute thalamic ischemic stroke and healthy subjects. Electroencephalography (EEG) in resting condition with eyes closed was recorded for 12 stroke patients and 11 healthy subjects as control group. Lempel-Ziv complexity (LZC), Sample Entropy (SampEn), and brain network using partial directed coherence (PDC) were calculated for feature extraction. Results showed that patients had increased mean LZC and SampEn than the controls, which implied the stroke group has higher EEG complexity. For the brain network, the stroke group displayed a trend of weaker cortical connectivity, which suggests a functional impairment of information transmission in cortical connections in stroke patients. These findings suggest that nonlinear analysis and brain network could provide essential information for better understanding the brain dysfunction in the stroke and assisting monitoring or prognostication of stroke evolution.

Fixed Dose IV rt-PA and Clinical Outcome in Ischemic Stroke Patients With Body Weight >100 kg: Pooled Data From 3 Randomized Clinical Trials

2018 ◽  
Vol 27 (10) ◽  
pp. 2843-2848
Author(s):  
Shahram Majidi ◽  
Christopher R. Leon Guerrero ◽  
Kathleen M. Burger ◽  
Dimitri Sigounas ◽  
Wayne J. Olan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Body Weight ◽  
Ischemic Stroke ◽  
Clinical Outcome ◽  
Randomized Clinical Trials ◽  
Fixed Dose ◽  
Stroke Patients ◽  
Pooled Data

scholarly journals A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia

2000 ◽  
Vol XXXII (3-4) ◽  
pp. 76-76
Author(s):  
J. Yrjanheikki ◽  
T. Tikka ◽  
R. Keinanen ◽  
G. Goldsteins ◽  
P. H. Chan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Acute Ischemic Stroke ◽  
Brain Tissue ◽  
Focal Cerebral Ischemia ◽  
The Brain ◽  
Tetracycline Derivative

One of the reasons for the insufficient effectiveness of treatment of acute ischemic stroke may be secondary inflammation of the brain tissue, which, according to the results of modern studies, significantly worsens the consequences and outcome of the disease.

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