scholarly journals The Need for New Biomarkers to Assist with Stroke Prevention and Prediction of Post-Stroke Therapy Based on Plasma-Derived Extracellular Vesicles

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1226
Author(s):  
Mircea Popescu Driga ◽  
Bogdan Catalin ◽  
Denisa Greta Olaru ◽  
Agnieszka Slowik ◽  
Nikolaus Plesnila ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Extracellular Vesicles ◽  
Cellular Responses ◽  
Blood Stream ◽  
Stroke Recovery ◽  
Brain Cells ◽  
Stroke Event ◽  
Post Stroke ◽  
Patients At Risk ◽  
The Brain

The risk of having a stroke event doubles each decade after the age of 55. Therefore, it is of great interest to develop neurorestorative therapies of stroke which occurs mostly in elderly people. However, to date, patients at risk for these sequels of stroke are not duly diagnosed and treated due to the lack of reliable biomarkers. Extracellular vesicles (EVs) are lipid bilayer-delimited particles that are shed by the brain cells and are able to cross the blood–brain barrier and enter the blood stream; thus, they may be used to interrogate molecular and cellular events in the brain damaged area. In this review, we summarize the major molecular and cellular responses of astroglia and neurons to cerebral ischemia and assess their impact on post-stroke recovery and rehabilitation. In particular, we ask if EVs secreted by brain cells are responses to cerebral ischemia, and they may shed new light on the interplay between exosomes-mediated interactions between brain cells and the question of how to exploit it in order to predict the individual course of the disease and to introduce specific preventive or therapeutic strategies. Given these findings, we are left with two options: either to (i) transplant neuronal precursors into the damaged cortical area or (ii) to covert abundantly present proliferating astrocytes in the perilesional area into neurons by using recently developed genetic technologies. However, given the complexity of molecular and cellular responses to cerebral ischemia and our limited capabilities to restore brain structure and function, we are left with only one realistic aim: to invest more in prevention.

scholarly journals Post-Stroke Social Isolation Reduces Cell Proliferation in the Dentate Gyrus and Alters miRNA Profiles in the Aged Female Mice Brain

2020 ◽  
Vol 22 (1) ◽  
pp. 99
Author(s):  
Aleah Holmes ◽  
Yan Xu ◽  
Juneyoung Lee ◽  
Michael E. Maniskas ◽  
Liang Zhu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Dentate Gyrus ◽  
Social Isolation ◽  
Census Data ◽  
Elderly Women ◽  
Stroke Recovery ◽  
Tissue Loss ◽  
Female Mice ◽  
Post Stroke ◽  
The Brain

Social isolation and loneliness are risk factors for stroke. Elderly women are more likely to be isolated. Census data shows that in homeowners over the age of 65, women are much more likely to live alone. However, the underlying mechanisms of the detrimental effects of isolation have not been well studied in older females. In this study, we hypothesized that isolation impairs post-stroke recovery in aged female mice, leading to dysregulated microRNAs (miRNAs) in the brain, including those previously shown to be involved in response to social isolation (SI). Aged C57BL/6 female mice were subjected to a 60-min middle cerebral artery occlusion and were randomly assigned to either single housing (SI) or continued pair housing (PH) immediately after stroke for 15 days. SI immediately after stroke led to significantly more brain tissue loss after stroke and higher mortality. Furthermore, SI significantly delayed motor and sensory recovery and worsened cognitive function, compared to PH. A decrease in cell proliferation was seen in the dentate gyrus of SI mice assessed by bromodeoxyuridine (BrdU) labeling. miRNAome data analysis revealed changes in several miRNAs in the brain, such as miR-297a-3p and miR-200c-3p, which are known to regulate pathways involved in cell proliferation. In conclusion, our data suggest that SI can lead to a poor post-stroke recovery in aged females and dysregulation of miRNAs and reduced hippocampal cell proliferation.

scholarly journals Extracellular Vesicles in Regeneration and Rehabilitation Recovery after Stroke

Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 843
Author(s):  
Alice Gualerzi ◽  
Silvia Picciolini ◽  
Francesca Rodà ◽  
Marzia Bedoni
Keyword(s):  
Extracellular Vesicles ◽  
Optimal Recovery ◽  
Special Focus ◽  
Stroke Event ◽  
Injured Brain ◽  
Long Time ◽  
Inflammatory Processes ◽  
Complex Events ◽  
The Brain ◽  
Potential Therapeutics

Patients that survive after a stroke event may present disabilities that can persist for a long time or permanently after it. If stroke prevention fails, the prompt and combinatorial intervention with pharmacological and rehabilitation therapy is pivotal for the optimal recovery of patients and the reduction of disabilities. In the present review, we summarize some key features of the complex events that occur in the brain during and after the stroke event, with a special focus on extracellular vesicles (EVs) and their role as both carriers of biomarkers and potential therapeutics. EVs have already demonstrated their ability to be used for diagnostic purposes for multiple brain disorders and could represent valuable tools to track the regenerative and inflammatory processes occurring in the injured brain after stroke. Last, but not least, the use of artificial or stem cell-derived EVs were proved to be effective in stimulating brain remodeling and ameliorating recovery after stroke. Still, effective biomarkers of recovery are needed to design robust trials for the validation of innovative therapeutic strategies, such as regenerative rehabilitation approaches.

Abstract T P279: Recognizing Depression in the Stroke Patient

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Rose M Donnelly ◽  
Jo-Ann Burns
Keyword(s):  
Stroke Patient ◽  
Screening Tool ◽  
Gap Analysis ◽  
Stroke Recovery ◽  
Depression Screening ◽  
Depression Symptoms ◽  
Post Stroke ◽  
Patient Health ◽  
Patients At Risk ◽  
Comprehensive Stroke Center

Depression is a frequent sequela of stroke that has been associated with poor recovery and rehabilitation response. Clinical depression may occur within 3 months post stroke and can last for several years if left untreated. Utilization of a depression screen helps identify patients at risk for post-stroke depression. It is important to recognize and treat depression symptoms early to improve patient outcomes. In performing a gap analysis in preparation for our survey for Comprehensive Stroke Center Certification, it became apparent this psychological aspect of patients was not being met. A systemic literature review was performed in search of a depression screening tool that was easy to use and addressed the needs of the patient. The tool chosen is the validated 2-item Patient Health Questionnaire depression module (PHQ-2). This depression screen is also utilized in our rehabilitation center which enhances the communication between our facilities. After educating all the neuroscience nursing staff and stroke physicians, the tool became part of the patient assessment. The nurse screens each stroke patient on admission to the division or transfer from the intensive care unit. If the patient scores 3 or greater, the physician is notified so appropriate follow-up and treatment can occur. If a patient is unable to be assessed, the physician is notified so other depression assessment measures can be considered. The utilization of a depression screening tool along with staff education has increased our staff’s awareness of the potential devastating effects depression can have on stroke recovery.

Abstract W P176: Self-reported Pre-Stroke Physical Activity Levels Influence Functional Ability Following Incident Stroke

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Michelle N McDonnell ◽  
Susan L Hillier ◽  
David L Roth ◽  
Suzanne E Judd ◽  
William E Haley ◽  
...  
Keyword(s):  
Physical Activity ◽  
Racial Differences ◽  
Functional Ability ◽  
Length Of Hospital Stay ◽  
Stroke Recovery ◽  
Activity Levels ◽  
Stroke Event ◽  
Stroke Incidence ◽  
Post Stroke ◽  
One Year

Background and Purpose: Emerging evidence suggests that stroke recovery is influenced by pre-stroke physical activity (PA). The purpose of this study was to examine whether prospectively collected pre-stroke PA levels were associated with functioning one year post-stroke in survivors of a first stroke. Methods: PA was assessed during baseline interviews of participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) observational study. Participants who experienced a first-ever stroke event during follow up were enrolled in an ancillary study. Approximately 12 months following stroke incidence, survivors and their informants were interviewed by telephone, and an in-home assessment of functional ability was conducted (n = 203). The association between pre-stroke PA and post-stroke function was assessed. Results: Participants reported baseline PA as either no vigorous PA (n = 65), or PA once or more per week (n = 138). Individuals who exercised at least once per week had significantly greater function at one year following stroke as assessed with the NIHSS, the Barthel Index and the Stroke Impact Scale physical domain score. In the multivariate model, race, education, sex, age, length of hospital stay and discharge destination were associated with functioning and attenuated this relationship. However, the significant association between pre-stroke PA and the NIHSS remained (p = 0.003). Conclusions: Self-reported PA prior to stroke was associated with significantly lower NIHSS scores one year after stroke. Other physical function measures were attenuated by factors such as female sex and African American race which were strongly related to poorer function.

scholarly journals Neuroinflammation in Post-Ischemic Neurodegeneration of the Brain: Friend, Foe, or Both?

2021 ◽  
Vol 22 (9) ◽  
pp. 4405
Author(s):  
Ryszard Pluta ◽  
Sławomir Januszewski ◽  
Stanisław J. Czuczwar
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Treatment Strategies ◽  
Systemic Circulation ◽  
The Other ◽  
Brain Cells ◽  
Potential Treatment ◽  
Ischemic Brain ◽  
The Many ◽  
The Brain

One of the leading causes of neurological mortality, disability, and dementia worldwide is cerebral ischemia. Among the many pathological phenomena, the immune system plays an important role in the development of post-ischemic degeneration of the brain, leading to the development of neuroinflammatory changes in the brain. After cerebral ischemia, the developing neuroinflammation causes additional damage to the brain cells, but on the other hand it also plays a beneficial role in repair activities. Inflammatory mediators are sources of signals that stimulate cells in the brain and promote penetration, e.g., T lymphocytes, monocytes, platelets, macrophages, leukocytes, and neutrophils from systemic circulation to the brain ischemic area, and this phenomenon contributes to further irreversible ischemic brain damage. In this review, we focus on the issues related to the neuroinflammation that occurs in the brain tissue after ischemia, with particular emphasis on ischemic stroke and its potential treatment strategies.

scholarly journals The Protective and Reparative Role of Colony Stimulating Factors in the Brain with Cerebral Ischemia / Reperfusion Injury

2020 ◽  
Author(s):  
Aysha Mohamed Rafik Patel ◽  
Nattayaporn Apaiajai ◽  
Nipon Chattipakorn ◽  
Siriporn Chattipakorn
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Clinical Indication ◽  
Colony Stimulating Factor ◽  
Stroke Therapy ◽  
Post Stroke ◽  
Cerebral Ischemia Reperfusion ◽  
The Brain ◽  
Stimulating Factor

Stroke is a debilitating disease and has the ability to culminate in devastating clinical outcomes. Ischemic stroke followed by reperfusion entrains cerebral ischemia / reperfusion (I/R) injury, which is a complex pathological process and is associated with serious clinical manifestations. Therefore, the development of a robust and effective post-stroke therapy is crucial. Granulocyte colony stimulating factor (GCSF) and erythropoietin (EPO), originally discovered as hematopoietic growth factors, are versatile and have transcended beyond their traditional role of orchestrating the proliferation, differentiation and survival of hematopoietic progenitors to one that fosters brain protection/ neuroregeneration. The clinical indication regarding GCSF and EPO as an auspicious therapeutic strategy is conferred in a plethora of illnesses, including anemia and neutropenia. EPO and GCSF alleviate cerebral I/R injury through a multitude of mechanisms, involving anti-apoptotic, anti-inflammatory, antioxidant, neurogenic and angiogenic effects. Despite bolstering evidence from preclinical studies, the multiple brain protective modalities of GCSF and EPO failed to translate in clinical trials and thereby raises several questions. The present review comprehensively compiles and discusses key findings from in vitro, in vivo and clinical data pertaining to the administration of EPO, GCSF, and other drugs which alter levels of colony stimulating factor (CSF) in the brain following cerebral I/R injury and elaborates on the contributing factors which led to the lost in translation of CSFs from bench to bedside. Any controversial findings are discussed to enable a clear overview of the role of EPO and GCSF as robust and effective candidates for post-stroke therapy.

scholarly journals Neurorehabilitation Potentials of Repetitive Transcranial Magnetic Stimulation in Post-stroke Motor and Speech Recovery

2019 ◽  
Author(s):  
Henry Liu
Keyword(s):  
Ischemic Stroke ◽  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Neuronal Excitability ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Stroke Recovery ◽  
Post Stroke ◽  
Speech Rehabilitation ◽  
Cortical Regions ◽  
The Brain

Ischemic stroke is a consequence of diminished cerebral blood flow to cortical regions, resulting in subsequent reductions in excitability. The brain undergoes immense cortical remapping following a stroke, which can be facilitated by neuronal excitability. However, analyses of electrophysiologic recordings, cortical stimulation, and fMRI reveal a decline in the excitability of the ipsilesional hemisphere following an ischemic stroke and an increase in interhemispheric inhibition by the contralesional hemisphere. Recent findings have implicated non-invasive stimulation with post-stroke recovery through the induction of synaptic plasticity and recruitment of neurotrophic factors to the peri-infarct region. The aim of this paper is to review recent research that has beendevoted to repetitive transcranial magnetic stimulation (rTMS) and its use as a therapeutic tool in motor and speech rehabilitation via the alteration of excitability in the brain post-ischemic stroke. 

scholarly journals Through the Open Window: How Does the Brain Talk to the Body?

2021 ◽  
Vol 9 ◽  
Author(s):  
Ludmila Gordon ◽  
Gil Levkowitz
Keyword(s):  
Blood Pressure ◽  
Blood Vessels ◽  
Blood Stream ◽  
The State ◽  
The Body ◽  
Brain Cells ◽  
Open Window ◽  
Food Digestion ◽  
The Brain ◽  
Sleep Cycles

The brain controls the activities of the body, including food digestion, drinking, sleep cycles, temperature, blood pressure, and more. These functions are essential to keep the body in homeostasis, which is the state of being steady and balanced. To control homeostasis, the brain talks to the body with the help of chemical messengers called hormones. Hormones travel through the blood stream from the brain to the body and back. However, in order to protect the delicate brain cells from unwanted intrusions, the blood vessels of the brain are tightly sealed, preventing the passage of most molecules. How, then, does the brain bypass this barrier to communicate with the body? The answer is that, in certain parts of the brain, the blood vessels contain special window-like openings that allow passage of hormones. Scientists are investigating why and how some blood vessels open their windows while others remain sealed.

Presence of antibody in virus-infected brain cells of SSPE ferrets

1983 ◽  
Vol 41 ◽  
pp. 804-805
Author(s):  
Hannah R. Brown ◽  
Tammy L. Donato ◽  
Halldor Thormar
Keyword(s):  
Measles Virus ◽  
Plasma Cells ◽  
Subacute Sclerosing Panencephalitis ◽  
Protein A ◽  
Neutralizing Antibody ◽  
Brain Cells ◽  
Antibody Titers ◽  
A Cell ◽  
The Central Nervous System ◽  
The Brain

Measles virus specific immunoglobulin G (IgG) has been found in the brains of patients with subacute sclerosing panencephalitis (SSPE), a slowly progressing disease of the central nervous system (CNS) in children. IgG/albumin ratios indicate that the antibodies are synthesized within the CNS. Using the ferret as an animal model to study the disease, we have been attempting to localize the Ig's in the brains of animals inoculated with a cell associated strain of SSPE. In an earlier report, preliminary results using Protein A conjugated to horseradish peroxidase (PrAPx) (Dynatech Diagnostics Inc., South Windham, ME.) to detect antibodies revealed the presence of immunoglobulin mainly in antibody-producing plasma cells in inflammatory lesions and not in infected brain cells.In the present experiment we studied the brain of an SSPE ferret with neutralizing antibody titers of 1:1024 in serum and 1:512 in CSF at time of sacrifice 7 months after i.c. inoculation with SSPE measles virus-infected cells. The animal was perfused with saline and portions of the brain and spinal cord were immersed in periodate-lysine-paraformaldehyde (P-L-P) fixative. The ferret was not perfused with fixative because parts of the brain were used for virus isolation.

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