scholarly journals Optimizing functional outcome endpoints for stroke recovery studies

2019 ◽  
Vol 39 (12) ◽  
pp. 2323-2342 ◽  
Author(s):  
Mustafa Balkaya ◽  
Sunghee Cho
Keyword(s):  
Animal Models ◽  
Functional Outcome ◽  
Recovery Of Function ◽  
Emotional Disturbances ◽  
Stroke Recovery ◽  
Preclinical Research ◽  
Stroke Research ◽  
Recovery Potential ◽  
Functional Outcome Measures ◽  
The Brain

Novel therapeutic intervention that aims to enhance the endogenous recovery potential of the brain during the subacute phase of stroke has produced promising results. The paradigm shift in treatment approaches presents new challenges to preclinical and clinical researchers alike, especially in the functional endpoints domain. Shortcomings of the “neuroprotection” era of stroke research are yet to be fully addressed. Proportional recovery observed in clinics, and potentially in animal models, requires a thorough reevaluation of the methods used to assess recovery. To this end, this review aims to give a detailed evaluation of functional outcome measures used in clinics and preclinical studies. Impairments observed in clinics and animal models will be discussed from a functional testing perspective. Approaches needed to bridge the gap between clinical and preclinical research, along with potential means to measure the moving target recovery, will be discussed. Concepts such as true recovery of function and compensation and methods that are suitable for distinguishing the two are examined. Often-neglected outcomes of stroke, such as emotional disturbances, are discussed to draw attention to the need for further research in this area.

scholarly journals Neuroplasticity Mechanisms and Prospects for Personalized Rehabilitation Strategies in Patients with Motor and Cognitive Impairments

2021 ◽  
Vol 20 (5) ◽  
pp. 37-46
Author(s):  
Kristina A. Shagaeva ◽  
Artur S. Shagaev
Keyword(s):  
Individual Characteristics ◽  
Micro Rna ◽  
Stroke Recovery ◽  
Cerebral Stroke ◽  
Motor Impairments ◽  
Genetic Characteristics ◽  
Positive Effects ◽  
Recovery Potential ◽  
The Brain ◽  
Rehabilitation Strategies

Aim. To highlight the most important areas of research on the problems of rehabilitation after stroke and the prospects for the development of new rehabilitation strategies, taking into account individual characteristics. Neuroplastic outcomes of anemic infarctions are presented by multi-pattern positive processes of synaptogenesis, sprouting, synthesis of neuroprotective proteins, and destructive effects of stress plasticity inducing dystonic disturbances, deterioration of stabilometric parameters and locomotor gait mechanisms with support deterioration [1]. Thus, specialists in neurorehabilitation should know the basics of fundamental neurophysiological processes in the central nervous system, interhemispheric networks of the brain, and optimize rehabilitation programs, taking into account individualized recovery profiles [2]. One of the factors influencing recovery after a stroke is nervous reorganization, which is proportional to the amount of damage [3]. The processes of neuroplasticity are studied from the standpoint of returning to the pre-stroke recovery model (with minor injuries) – forming “optimal” plasticity and compensatory strategies of “destructive” plasticity (with extensive hemispheric injuries). Micro-RNA (miRNA) are understudied in the neuroprotective reaction to cerebral ischemia. Another important modulator of stroke outcomes is the brain-derived neurotrophic factor (BDNF). Processing of the defective BDNF synthesis when the amino acid valine is replaced by methionine (val-met) that occurs during allelic disorders is of outstanding interest. Conclusion. Promising research areas for strategic approaches to rehabilitation after a stroke are the study of hemispheric introduction, miRNA and neuroprotection cascades; BDNF as an inducer of neuronal differentiation. Allelic BDNF polymorphisms induce lower recovery potential after stroke. Under certain environmental conditions motor learning can overcome the neuroplasticity deficit in the BDNF gene polymorphism. The studies have shown general patterns of positive effects of aerobic stimuli with enhanced BDNF secretion in the recovery of patients with cognitive and motor impairments; nevertheless, the onset period, intensity, duration and exercises rhythmicity have not been established in cerebral stroke. Future studies are likely to optimize rehabilitation profiles based on genetic characteristics.

scholarly journals Variability of functional outcome measures used in animal models of stroke and vascular cognitive impairment – a review of contemporary studies

2018 ◽  
Vol 38 (11) ◽  
pp. 1872-1884 ◽  
Author(s):  
Tuuli M Hietamies ◽  
Caroline Ostrowski ◽  
Zhong Pei ◽  
Luyang Feng ◽  
Christopher McCabe ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Functional Outcome ◽  
Outcome Measures ◽  
Vascular Cognitive Impairment ◽  
Regulatory Agencies ◽  
Preclinical Research ◽  
Outcome Set ◽  
Core Set ◽  
Functional Assessments ◽  
Functional Outcome Measures

Despite promising preclinical data, few novel stroke therapies have shown efficacy in man. Efforts to improve standards in conduct and reporting of preclinical research are ongoing. In clinical trials, inconsistency in outcome measures led to regulatory agencies and funders mandating use of a core set of functional outcomes. Our aim was to describe functional outcome measures in preclinical stroke and vascular cognitive impairment (VCI) studies. From 14 high impact journals (January 2005–December 2015 inclusive), 91,956 papers were screened with 1302 full texts analyzed for stroke (ischemic and hemorrhagic) and 56 for VCI studies. In total, 636 (49%) stroke and 37 (66%) VCI papers reported functional outcome measures. There were 74 different functional assessments reported in stroke and 20 in VCI studies. Neurological deficit scores (74%) and Morris water maze (60%) were most commonly used in stroke and VCI, respectively. However, inconsistencies in methods used to assess and score recovery were noted. Neurological and behavioural functional outcome measures are increasingly used in preclinical stroke or VCI studies; however, there is substantial variation in methods. A strict standardized outcome set may not be suitable for translational work, but greater consistency in choice, application and reporting of outcomes may improve the science.

scholarly journals Principles and requirements for stroke recovery science

2020 ◽  
pp. 0271678X2097004
Author(s):  
Clemens J Sommer ◽  
Wolf-Rüdiger Schäbitz
Keyword(s):  
Molecular Mechanisms ◽  
Time Window ◽  
Stroke Recovery ◽  
Therapeutic Interventions ◽  
Good Time ◽  
Detailed Knowledge ◽  
Post Stroke ◽  
Stroke Research ◽  
Recovery Potential ◽  
Neuroprotective Strategies

The disappointing results in bench-to-bedside translation of neuroprotective strategies caused a certain shift in stroke research towards enhancing the endogenous recovery potential of the brain. One reason for this focus on recovery is the much wider time window for therapeutic interventions which is open for at least several months. Since recently two large clinical studies using d-amphetamine or fluoxetine, respectively, to enhance post-stroke neurological outcome failed again it is a good time for a critical reflection on principles and requirements for stroke recovery science. In principal, stroke recovery science deals with all events from the molecular up to the functional and behavioral level occurring after brain ischemia eventually ending up with any measurable improvement of various clinical parameters. A detailed knowledge of the spontaneously occurring post-ischemic regeneration processes is the indispensable prerequisite for any therapeutic approaches aiming to modify these responses to enhance post-stroke recovery. This review will briefly illuminate the molecular mechanisms of post-ischemic regeneration and the principle possibilities to foster post-stroke recovery. In this context, recent translational approaches are analyzed. Finally, the principal and specific requirements and pitfalls in stroke recovery research as well as potential explanations for translational failures will be discussed.

Abstract TP420: Variability in Functional Outcome Measures Used in Contemporary Animal Models of Stroke and Vascular Cognitive Impairment

Stroke ◽  
2018 ◽  
Vol 49 (Suppl_1) ◽  
Author(s):  
Tuuli M Hietamies ◽  
Caroline Ostrowski ◽  
Pei Zhong ◽  
Luyang Feng ◽  
Lorraine M Work ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Animal Models ◽  
Functional Outcome ◽  
Outcome Measures ◽  
Vascular Cognitive Impairment ◽  
Functional Outcome Measures

Animal models of alcohol use disorder and the brain: From casual drinking to dependence.

2019 ◽  
Vol 5 (3) ◽  
pp. 222-242 ◽  
Author(s):  
Nicole A. Crowley ◽  
Nigel C. Dao ◽  
Sarah N. Magee ◽  
Alexandre J. Bourcier ◽  
Emily G. Lowery-Gionta
Keyword(s):  
Alcohol Use ◽  
Animal Models ◽  
Alcohol Use Disorder ◽  
The Brain

scholarly journals Are We Paving the Way to Dig Out of the “Pandemic Hole”? A Narrative Review on SARS-CoV-2 Vaccination: From Animal Models to Human Immunization

2021 ◽  
Vol 9 (3) ◽  
pp. 53
Author(s):  
Giuseppe Tardiolo ◽  
Pina Brianti ◽  
Daniela Sapienza ◽  
Pia dell’Utri ◽  
Viviane Di Dio ◽  
...  
Keyword(s):  
Animal Models ◽  
Viral Vector ◽  
Herd Immunity ◽  
Population Level ◽  
Narrative Review ◽  
Therapeutic Interventions ◽  
Preclinical Research ◽  
Inactivated Vaccines ◽  
Preclinical And Clinical Studies ◽  
Social Upheaval

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new pathogen agent causing the coronavirus infectious disease (COVID-19). This novel virus originated the most challenging pandemic in this century, causing economic and social upheaval internationally. The extreme infectiousness and high mortality rates incentivized the development of vaccines to control this pandemic to prevent further morbidity and mortality. This international scenario led academic scientists, industries, and governments to work and collaborate strongly to make a portfolio of vaccines available at an unprecedented pace. Indeed, the robust collaboration between public systems and private companies led to resolutive actions for accelerating therapeutic interventions and vaccines mechanism. These strategies contributed to rapidly identifying safe and effective vaccines as quickly and efficiently as possible. Preclinical research employed animal models to develop vaccines that induce protective and long-lived immune responses. A spectrum of vaccines is worldwide under investigation in various preclinical and clinical studies to develop both individual protection and safe development of population-level herd immunity. Companies employed and developed different technological approaches for vaccines production, including inactivated vaccines, live-attenuated, non-replicating viral vector vaccines, as well as acid nucleic-based vaccines. In this view, the present narrative review provides an overview of current vaccination strategies, taking into account both preclinical studies and clinical trials in humans. Furthermore, to better understand immunization, animal models on SARS-CoV-2 pathogenesis are also briefly discussed.

scholarly journals Is There a Brain Microbiome?

2021 ◽  
Vol 16 ◽  
pp. 263310552110187
Author(s):  
Christopher D Link
Keyword(s):  
Animal Models ◽  
Human Brain ◽  
Neurodegenerative Diseases ◽  
Ground Truth ◽  
Healthy Human ◽  
Strong Motivation ◽  
The Many ◽  
The Brain

Numerous studies have identified microbial sequences or epitopes in pathological and non-pathological human brain samples. It has not been resolved if these observations are artifactual, or truly represent population of the brain by microbes. Given the tempting speculation that resident microbes could play a role in the many neuropsychiatric and neurodegenerative diseases that currently lack clear etiologies, there is a strong motivation to determine the “ground truth” of microbial existence in living brains. Here I argue that the evidence for the presence of microbes in diseased brains is quite strong, but a compelling demonstration of resident microbes in the healthy human brain remains to be done. Dedicated animal models studies may be required to determine if there is indeed a “brain microbiome.”

scholarly journals Thymoquinone and Curcumin Defeat Aging-Associated Oxidative Alterations Induced by D-Galactose in Rats’ Brain and Heart

2021 ◽  
Vol 22 (13) ◽  
pp. 6839
Author(s):  
Ali H. El-Far ◽  
Yaser H. A. Elewa ◽  
Elsayeda-Zeinab A. Abdelfattah ◽  
Abdel-Wahab A. Alsenosy ◽  
Mustafa S. Atta ◽  
...  
Keyword(s):  
Animal Models ◽  
Calcium Binding ◽  
Caspase 3 ◽  
Combination Group ◽  
Preventive Effect ◽  
Group Data ◽  
Adapter Molecule ◽  
The Brain ◽  
Bcl2 Expression

D-galactose (D-gal) administration causes oxidative disorder and is widely utilized in aging animal models. Therefore, we subcutaneously injected D-gal at 200 mg/kg BW dose to assess the potential preventive effect of thymoquinone (TQ) and curcumin (Cur) against the oxidative alterations induced by D-gal. Other than the control, vehicle, and D-gal groups, the TQ and Cur treated groups were orally supplemented at 20 mg/kg BW of each alone or combined. TQ and Cur effectively suppressed the oxidative alterations induced by D-gal in brain and heart tissues. The TQ and Cur combination significantly decreased the elevated necrosis in the brain and heart by D-gal. It significantly reduced brain caspase 3, calbindin, and calcium-binding adapter molecule 1 (IBA1), heart caspase 3, and BCL2. Expression of mRNA of the brain and heart TP53, p21, Bax, and CASP-3 were significantly downregulated in the TQ and Cur combination group along with upregulation of BCL2 in comparison with the D-gal group. Data suggested that the TQ and Cur combination is a promising approach in aging prevention.

scholarly journals Biomarkers of Angiogenesis and Neuroplasticity as Promising Clinical Tools for Stroke Recovery Evaluation

2021 ◽  
Vol 22 (8) ◽  
pp. 3949
Author(s):  
Lidia Wlodarczyk ◽  
Rafal Szelenberger ◽  
Natalia Cichon ◽  
Joanna Saluk-Bijak ◽  
Michal Bijak ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Stroke Recovery ◽  
Clinical Scales ◽  
Recovery Processes ◽  
Recovery Potential ◽  
Current State ◽  
Standard Procedures ◽  
Key Issues ◽  
Clinical Tools ◽  
Selection Of

Several key issues impact the clinical practice of stroke rehabilitation including a patient’s medical history, stroke experience, the potential for recovery, and the selection of the most effective type of therapy. Until clinicians have answers to these concerns, the treatment and rehabilitation are rather intuitive, with standard procedures carried out based on subjective estimations using clinical scales. Therefore, there is a need to find biomarkers that could predict brain recovery potential in stroke patients. This review aims to present the current state-of-the-art stroke recovery biomarkers that could be used in clinical practice. The revision of biochemical biomarkers has been developed based on stroke recovery processes: angiogenesis and neuroplasticity. This paper provides an overview of the biomarkers that are considered to be ready-to-use in clinical practice and others, considered as future tools. Furthermore, this review shows the utility of biomarkers in the development of the concept of personalized medicine. Enhancing brain neuroplasticity and rehabilitation facilitation are crucial concerns not only after stroke, but in all central nervous system diseases.

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