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.

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 Obstructive Sleep Apnea and Inflammation: Proof of Concept Based on Two Illustrative Cytokines

2019 ◽  
Vol 20 (3) ◽  
pp. 459 ◽  
Author(s):  
Leila Kheirandish-Gozal ◽  
David Gozal
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Inflammatory Diseases ◽  
Sleep Apnea Syndrome ◽  
Special Focus ◽  
Normal Body Mass Index ◽  
Low Grade ◽  
Obstructive Sleep ◽  
Inflammatory Processes ◽  
Factor Α

Obstructive sleep apnea syndrome (OSAS) is a markedly prevalent condition across the lifespan, particularly in overweight and obese individuals, which has been associated with an independent risk for neurocognitive, behavioral, and mood problems as well as cardiovascular and metabolic morbidities, ultimately fostering increases in overall mortality rates. In adult patients, excessive daytime sleepiness (EDS) is the most frequent symptom leading to clinical referral for evaluation and treatment, but classic EDS features are less likely to be reported in children, particularly among those with normal body-mass index. The cumulative evidence collected over the last two decades supports a conceptual framework, whereby sleep-disordered breathing in general and more particularly OSAS should be viewed as low-grade chronic inflammatory diseases. Accordingly, it is assumed that a proportion of the morbid phenotypic signature in OSAS is causally explained by underlying inflammatory processes inducing end-organ dysfunction. Here, the published links between OSAS and systemic inflammation will be critically reviewed, with special focus on the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), since these constitute classical prototypes of the large spectrum of inflammatory molecules that have been explored in OSAS patients.

scholarly journals Intermittent Hypoxic Conditioning Rescues Cognition and Mitochondrial Bioenergetic Profile in the Triple Transgenic Mouse Model of Alzheimer’s Disease

2021 ◽  
Vol 22 (1) ◽  
pp. 461
Author(s):  
Sónia C. Correia ◽  
Nuno J. Machado ◽  
Marco G. Alves ◽  
Pedro F. Oliveira ◽  
Paula I. Moreira
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Brain Cortex ◽  
Neurodegenerative Disorder ◽  
Special Focus ◽  
Mitochondrial Bioenergetics ◽  
Related Phenotype ◽  
Brain Resilience ◽  
The Brain

The lack of effective disease-modifying therapeutics to tackle Alzheimer’s disease (AD) is unsettling considering the actual prevalence of this devastating neurodegenerative disorder worldwide. Intermittent hypoxic conditioning (IHC) is a powerful non-pharmacological procedure known to enhance brain resilience. In this context, the aim of the present study was to investigate the potential long-term protective impact of IHC against AD-related phenotype, putting a special focus on cognition and mitochondrial bioenergetics and dynamics. For this purpose, six-month-old male triple transgenic AD mice (3×Tg-AD) were submitted to an IHC protocol for two weeks and the behavioral assessment was performed at 8.5 months of age, while the sacrifice of mice occurred at nine months of age and their brains were removed for the remaining analyses. Interestingly, IHC was able to prevent anxiety-like behavior and memory and learning deficits and significantly reduced brain cortical levels of amyloid-β (Aβ) in 3×Tg-AD mice. Concerning brain energy metabolism, IHC caused a significant increase in brain cortical levels of glucose and a robust improvement of the mitochondrial bioenergetic profile in 3×Tg-AD mice, as mirrored by the significant increase in mitochondrial membrane potential (ΔΨm) and respiratory control ratio (RCR). Notably, the improvement of mitochondrial bioenergetics seems to result from an adaptative coordination of the distinct but intertwined aspects of the mitochondrial quality control axis. Particularly, our results indicate that IHC favors mitochondrial fusion and promotes mitochondrial biogenesis and transport and mitophagy in the brain cortex of 3×Tg-AD mice. Lastly, IHC also induced a marked reduction in synaptosomal-associated protein 25 kDa (SNAP-25) levels and a significant increase in both glutamate and GABA levels in the brain cortex of 3×Tg-AD mice, suggesting a remodeling of the synaptic microenvironment. Overall, these results demonstrate the effectiveness of the IHC paradigm in forestalling the AD-related phenotype in the 3×Tg-AD mouse model, offering new insights to AD therapy and forcing a rethink concerning the potential value of non-pharmacological interventions in clinical practice.

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.

scholarly journals Cytokine-Laden Extracellular Vesicles Predict Patient Prognosis after Cerebrovascular Accident

2021 ◽  
Vol 22 (15) ◽  
pp. 7847
Author(s):  
Anthony Fringuello ◽  
Philip D. Tatman ◽  
Tadeusz Wroblewski ◽  
John A. Thompson ◽  
Xiaoli Yu ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Inflammatory Cytokines ◽  
Hemorrhagic Stroke ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Interleukin 7 ◽  
Poor Outcomes ◽  
Patient Prognosis ◽  
The Brain

Background: A major contributor to disability after hemorrhagic stroke is secondary brain damage induced by the inflammatory response. Following stroke, global increases in numerous cytokines—many associated with worse outcomes—occur within the brain, cerebrospinal fluid, and peripheral blood. Extracellular vesicles (EVs) may traffic inflammatory cytokines from damaged tissue within the brain, as well as peripheral sources, across the blood–brain barrier, and they may be a critical component of post-stroke neuroinflammatory signaling. Methods: We performed a comprehensive analysis of cytokine concentrations bound to plasma EV surfaces and/or sequestered within the vesicles themselves. These concentrations were correlated to patient acute neurological condition by the Glasgow Coma Scale (GCS) and to chronic, long-term outcome via the Glasgow Outcome Scale-Extended (GOS-E). Results: Pro-inflammatory cytokines detected from plasma EVs were correlated to worse outcomes in hemorrhagic stroke patients. Anti-inflammatory cytokines detected within EVs were still correlated to poor outcomes despite their putative neuroprotective properties. Inflammatory cytokines macrophage-derived chemokine (MDC/CCL2), colony stimulating factor 1 (CSF1), interleukin 7 (IL7), and monokine induced by gamma interferon (MIG/CXCL9) were significantly correlated to both negative GCS and GOS-E when bound to plasma EV membranes. Conclusions: These findings correlate plasma-derived EV cytokine content with detrimental outcomes after stroke, highlighting the potential for EVs to provide cytokines with a means of long-range delivery of inflammatory signals that perpetuate neuroinflammation after stroke, thus hindering recovery.

scholarly journals Recovery of Brain in Chick Embryos by Growing Second Heart and Brain

2019 ◽  
Vol 7 (18) ◽  
pp. 3085-3089
Author(s):  
Massimo Fioranelli ◽  
Alireza Sepehri ◽  
Maria Grazia Roccia ◽  
Cota Linda ◽  
Chiara Rossi ◽  
...  
Keyword(s):  
Subventricular Zone ◽  
Blood Cells ◽  
Neural Circuits ◽  
Circulatory System ◽  
Egg Cell ◽  
Chick Embryos ◽  
Injured Brain ◽  
Embryo Heart ◽  
Healthy Part ◽  
The Brain

To recover chick embryos damaged the brain, two methods are presented. In both of them, somatic cells of an embryo introduced into an egg cell and an embryo have emerged. In one method, injured a part of the brain in the head of an embryo is replaced with a healthy part of the brain. In the second method, the heart of brain embryo dead is transplanted with the embryo heart. In this mechanism, new blood cells are emerged in the bone marrow and transmit information of transplantation to subventricular zone (SVZ) of the brain through the circulatory system. Then, SVZ produces new neural stem cells by a subsequent dividing into neurons. These neurons produce new neural circuits within the brain and recover the injured brain. To examine the model, two hearts of two embryos are connected, and their effects on neural circuits are observed.  

scholarly journals Micronuclei in blood lumphocytes of existing and former coal miners: evaluation of the effect of anthracosilicosis

2019 ◽  
Vol 17 (4) ◽  
pp. 57-64
Author(s):  
Vladimir G. Druzhinin ◽  
Svetlana V. Apalko ◽  
Elizaveta D. Baranova ◽  
Valentin P. Volobaev ◽  
Tatiana Yu. Drobchik ◽  
...  
Keyword(s):  
Coal Dust ◽  
Additional Contribution ◽  
Coal Miners ◽  
Genotoxic Effects ◽  
The Status ◽  
Long Time ◽  
Inflammatory Processes ◽  
Simultaneous Decrease ◽  
Genotoxic Risk ◽  
Cytogenetic Parameters

Background. The purpose of this study was to investigate the genotoxic risk in anthracosilicosis patients and in those with occupational exposure to coal dust. Materials and methods. We studied micronuclei (MN) and other cytogenetic lesions in blood lymphocytes in three groups of men comparable in age: 74 coal miners suffering from anthracosilicosis (AS), 41 healthy miners, and 70 control donors. Results. A significant increase in the frequency of MN was revealed with a simultaneous decrease in proliferative activity in samples of healthy and sick miners compared with the control. The level of MN in the lymphocytes of patients with AS significantly exceeded the corresponding indicator in the sample of healthy miners (1.22 0.05% versus 1.03 0.07%; p 0.01). The age of the subjects and the status of smoking did not have a significant effect on the frequency of cytogenetic parameters. Conclusion. AS in miners makes an additional contribution to the formation of DNA damage in lymphocytes. This contribution is probably due to oxidative stress accompanying inflammatory processes in pulmonary fibrosis. The results of the study also indicate the absence of differences in the frequency of MN when comparing subgroups of current and former miners. This means that the genotoxic effects in the lymphocytes of miners are able to persist for a long time after the termination of exposure by adverse factors in coal mining.

scholarly journals Extracellular vesicles (exosomes and ectosomes) play key roles in the pathology of brain diseases

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Jacopo Meldolesi
Keyword(s):  
Multiple Sclerosis ◽  
Extracellular Vesicles ◽  
Brain Diseases ◽  
Target Cells ◽  
Surface Binding ◽  
Cells Of Origin ◽  
Relapsing Remitting ◽  
And Function ◽  
The Brain

AbstractLast century, neurons and glial cells were mostly believed to play distinct functions, relevant for the brain. Progressively, however, it became clear that neurons, astrocytes and microglia co-operate intensely with each other by release/binding of signaling factors, direct surface binding and generation/release of extracellular vesicles, the exosomes and ectosomes, called together vesicles in this abstract. The present review is focused on these vesicles, fundamental in various brain diseases. Their properties are extraordinary. The specificity of their membrane governs their fusion with distinct target cells, variable depending on the state and specificity of their cells of origin and target. Result of vesicle fusion is the discharge of their cargos into the cytoplasm of target cells. Cargos are composed of critical molecules, from proteins (various nature and function) to nucleotides (especially miRNAs), playing critical roles in immune and neurodegenerative diseases. Among immune diseases is multiple sclerosis, affected by extensive dysregulation of co-trafficking neural and glial vesicles, with distinct miRNAs inducing severe or reducing effects. The vesicle-dependent differences between progressive and relapsing-remitting forms of the disease are relevant for clinical developments. In Alzheimer’s disease the vesicles can affect the brain by changing their generation and inducing co-release of effective proteins, such Aβ and tau, from neurons and astrocytes. Specific miRNAs can delay the long-term development of the disease. Upon their traffic through the blood-brainbarrier, vesicles of various origin reach fluids where they are essential for the identification of biomarkers, important for diagnostic and therapeutic innovations, critical for the future of many brain patients.

scholarly journals Fingolimod Rescues Memory and Improves Pathological Hallmarks in the 3xTg-AD Model of Alzheimer’s Disease

2022 ◽  
Author(s):  
Steven G. Fagan ◽  
Sibylle Bechet ◽  
Kumlesh K. Dev
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Biochemical Analysis ◽  
Spatial Working Memory ◽  
Cell Number ◽  
Model Of Alzheimer’S Disease ◽  
Candidate Drug ◽  
Inflammatory Processes ◽  
The Brain ◽  
Ad Mouse Model

AbstractTherapeutic strategies for Alzheimer’s disease (AD) have largely focused on the regulation of amyloid pathology while those targeting tau pathology, and inflammatory mechanisms are less explored. In this regard, drugs with multimodal and concurrent targeting of Aβ, tau, and inflammatory processes may offer advantages. Here, we investigate one such candidate drug in the triple transgenic 3xTg-AD mouse model of AD, namely the disease-modifying oral neuroimmunomodulatory therapeutic used in patients with multiple sclerosis, called fingolimod. In this study, administration of fingolimod was initiated after behavioral symptoms are known to emerge, at 6 months of age. Treatment continued to 12 months when behavioral tests were performed and thereafter histological and biochemical analysis was conducted on postmortem tissue. The results demonstrate that fingolimod reverses deficits in spatial working memory at 8 and 12 months of age as measured by novel object location and Morris water maze tests. Inflammation in the brain is alleviated as demonstrated by reduced Iba1-positive and CD3-positive cell number, less ramified microglial morphology, and improved cytokine profile. Finally, treatment with fingolimod was shown to reduce phosphorylated tau and APP levels in the hippocampus and cortex. These results highlight the potential of fingolimod as a multimodal therapeutic for the treatment of AD.

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