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.

Abstract P757: Social Isolation After Stroke Reduces Cell Proliferation and Alters Brain MiRNA Profiles in the Aged Female Mice

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Aleah Holmes ◽  
Yan Xu ◽  
Juneyoung Lee ◽  
Liang Zhu ◽  
Venugopal Reddy Venna ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Social Isolation ◽  
Elderly Women ◽  
Epidemiological Studies ◽  
Stroke Recovery ◽  
Tissue Loss ◽  
Adhesive Tape ◽  
Female Mice ◽  
Post Stroke ◽  
Hippocampal Cell

Background: Social isolation (SI) and loneliness are risk factors for stroke. Epidemiological studies have shown that women tend to have a higher risk of stroke at later age and elderly women are more likely to be isolated. The mechanisms underlying the detrimental effects of SI have not been well studied in older females. We hypothesized that SI in aged female mice would lead to impaired post-stroke recovery and could lead to differential regulation of microRNAs (miRNAs). Methods: In this study, aged C57BL/6N female mice were subjected to a 60-minute middle cerebral artery occlusion (MCAO) and were randomly assigned to either single housing (SI) or continued pair housing (PH) immediately after stroke for 15 days. Infarct size, mortality and recovery was assessed using open field, the adhesive-tape removal task and the Y-maze test. MiRNAs were comprehensively analyzed by miRNAome analysis on stroke brain, and changes in hippocampal cell proliferation was assessed from perfused brain sections. Results: Importantly, SI immediately after stroke led to significantly larger tissue loss and higher mortality in aged females, it also significantly delayed motor/sensory recovery in the adhesive removal test and impaired overall locomotor activity. In addition, these mice also demonstrated worse post-stroke cognitive function. In parallel, brains of these mice showed reduced miR-297a-3p expression and increased miR-18a-3p and miR-200c-3p expression with SI compared to PH cohort and reduced hippocampal cell proliferation. Conclusion: The results from this study suggest that SI after stroke can increase mortality and significantly impair post-stroke recovery in aged female mice. These worse outcomes are in parallel to the significant changes in several miRNAs and reduced hippocampal cell proliferation.

scholarly journals Growth Hormone Promotes Motor Function after Experimental Stroke and Enhances Recovery-Promoting Mechanisms within the Peri-Infarct Area

2020 ◽  
Vol 21 (2) ◽  
pp. 606 ◽  
Author(s):  
Sonia Sanchez-Bezanilla ◽  
N. David Åberg ◽  
Patricia Crock ◽  
Frederick R. Walker ◽  
Michael Nilsson ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cell Proliferation ◽  
Motor Function ◽  
Stroke Recovery ◽  
Tissue Loss ◽  
Pharmacological Intervention ◽  
Therapeutic Effects ◽  
Post Stroke ◽  
Positive Effects ◽  
Infarct Area

Motor impairment is the most common and widely recognised clinical outcome after stroke. Current clinical practice in stroke rehabilitation focuses mainly on physical therapy, with no pharmacological intervention approved to facilitate functional recovery. Several studies have documented positive effects of growth hormone (GH) on cognitive function after stroke, but surprisingly, the effects on motor function remain unclear. In this study, photothrombotic occlusion targeting the motor and sensory cortex was induced in adult male mice. Two days post-stroke, mice were administered with recombinant human GH or saline, continuing for 28 days, followed by evaluation of motor function. Three days after initiation of the treatment, bromodeoxyuridine was administered for subsequent assessment of cell proliferation. Known neurorestorative processes within the peri-infarct area were evaluated by histological and biochemical analyses at 30 days post-stroke. This study demonstrated that GH treatment improves motor function after stroke by 50%–60%, as assessed using the cylinder and grid walk tests. Furthermore, the observed functional improvements occurred in parallel with a reduction in brain tissue loss, as well as increased cell proliferation, neurogenesis, increased synaptic plasticity and angiogenesis within the peri-infarct area. These findings provide new evidence about the potential therapeutic effects of GH in stroke recovery.

Abstract TP104: Post Stroke Depressive-Like Behaviors in Middle-Aged Female Rats is Associated With Gut Dysbiosis and Improved by Mir363-3p

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Courtney Stewart ◽  
Aditya Panta ◽  
Taylor Branyan ◽  
Farida Sohrabji
Keyword(s):  
Cell Proliferation ◽  
Dentate Gyrus ◽  
Forced Swim Test ◽  
Female Rats ◽  
Middle Aged ◽  
16S Sequencing ◽  
Post Stroke ◽  
Hippocampal Cell ◽  
Affective Behaviors ◽  
Post Stroke Depression

Background: Post-stroke depression (PSD) occurs in one-third of stroke survivors, is more prevalent in women, and negatively impacts quality of life and recovery. Our previous work showed that acyclic middle-aged female rats display depressive behaviors after stroke, and IV treatment with mir363-3p attenuates these behaviors. Serotonin has been implicated in affective behaviors, and loss of this neurotransmitter is also associated with decreased neurogenesis in the hippocampus. The present study determined (a) whether stroke affected tryptophan, a gut metabolite, and precursor for serotonin, and cell proliferation in the hippocampus and (b) whether serum tryptophan levels and hippocampal cell proliferation was restored by mir363-3p. Methods: Ischemic stroke was induced by stereotaxic delivery of endothelin-1 to the MCA of middle-aged female rats. Animals received a single injection of mir363-3p or scrambled oligos 4h after stroke. Depressive-like behaviors were assessed by the Effort-based sucrose consumption test, Social Interaction and Forced Swim Test 3 months after stroke. Blood was collected at termination. Serum tryptophan levels were quantified by ELISA. Bacterial composition was analyzed by 16S sequencing of fecal samples. Ki67 immunohistochemistry was performed on brain tissue collected at termination and quantified within the dentate gyrus by two blind observers. Results: Animals subjected to stroke exhibited depressive-like behaviors and had decreased tryptophan levels as compared to sham treated animals. This is also accompanied by microbiota dysbiosis as measured by an elevated ratio of Firmicutes to Bacteroidetes. Mir363-3p treatment increased tryptophan levels as compared to scrambled controls and were no different from sham (non-stroke) animals. Moreover, miR363-3p treated rats exhibit a significantly more dentate gyrus-specific Ki67 expression a proliferation marker. Conclusions: Together, these data indicate that miR363-3p attenuates post stroke depression via a mechanism that prevents microbiota dysbiosis and increases hippocampal cell proliferation.

scholarly journals Corticosterone Administration Alters White Matter Tract Structure and Reduces Gliosis in the Sub-Acute Phase of Experimental Stroke

2021 ◽  
Vol 22 (13) ◽  
pp. 6693
Author(s):  
Katarzyna Zalewska ◽  
Rebecca J. Hood ◽  
Giovanni Pietrogrande ◽  
Sonia Sanchez-Bezanilla ◽  
Lin Kooi Ong ◽  
...  
Keyword(s):  
White Matter ◽  
Biochemical Analysis ◽  
Stroke Recovery ◽  
Tissue Loss ◽  
Experimental Stroke ◽  
White Matter Tract ◽  
Ipsilateral Hemisphere ◽  
Post Stroke ◽  
Sham Surgery ◽  
Prolonged Stress

White matter tract (WMT) degeneration has been reported to occur following a stroke, and it is associated with post-stroke functional disturbances. White matter pathology has been suggested to be an independent predictor of post-stroke recovery. However, the factors that influence WMT remodeling are poorly understood. Cortisol is a steroid hormone released in response to prolonged stress, and elevated levels of cortisol have been reported to interfere with brain recovery. The objective of this study was to investigate the influence of corticosterone (CORT; the rodent equivalent of cortisol) on WMT structure post-stroke. Photothrombotic stroke (or sham surgery) was induced in 8-week-old male C57BL/6 mice. At 72 h, mice were exposed to standard drinking water ± CORT (100 µg/mL). After two weeks of CORT administration, mice were euthanised and brain tissue collected for histological and biochemical analysis of WMT (particularly the corpus callosum and corticospinal tract). CORT administration was associated with increased tissue loss within the ipsilateral hemisphere, and modest and inconsistent WMT reorganization. Further, a structural and molecular analysis of the WMT components suggested that CORT exerted effects over axons and glial cells. Our findings highlight that CORT at stress-like levels can moderately influence the reorganization and microstructure of WMT post-stroke.

Microarray Profiling Reveals Distinct Circulating miRNAs in Aged Male and Female Mice Subjected to Post-stroke Social Isolation

2020 ◽  
Author(s):  
Anik Banerjee ◽  
Anil K. Chokkalla ◽  
Julia J. Shi ◽  
Juneyoung Lee ◽  
Venugopal Reddy Venna ◽  
...  
Keyword(s):  
Social Isolation ◽  
Circulating Mirnas ◽  
Male And Female ◽  
Female Mice ◽  
Post Stroke ◽  
Microarray Profiling

The continuum of connectedness and social isolation during post stroke recovery

2008 ◽  
Vol 22 (1) ◽  
pp. 54-64 ◽  
Author(s):  
Jolie Haun ◽  
Maude Rittman ◽  
Melanie Sberna
Keyword(s):  
Social Isolation ◽  
Stroke Recovery ◽  
Post Stroke ◽  
The Continuum

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.

Abstract WP110: Identification and Validation of a Unique Mirna Target Mir-141-3p in Post Stroke Socially Isolated Aged Mice

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Rajkumar Verma ◽  
Louise D McCullough
Keyword(s):  
Social Isolation ◽  
Post Treatment ◽  
Stroke Recovery ◽  
Motor Deficits ◽  
Dependent Manner ◽  
Total Rna ◽  
Post Stroke ◽  
Mrna Targets ◽  
Socially Isolated

Introduction: MicroRNAs (miRNAs) are a class of short non-coding RNAs that have been identified as a powerful interventional tool for many diseases, including stroke. Very recent studies have found that microRNAs also mediate aspects of social interaction. Social environments can directly influence miRNA expression, which then triggers a plethora of downstream gene changes. Social isolation (SI) impairs stroke recovery and leads to inflammation. We hypothesize that miRNAs are involved in the detrimental effects of post-stroke social isolation. Methods: Eighteen-month-old male C57BL/6 mice were pair housed (PH) for two weeks prior to stroke and randomly assigned to various housing conditions (ST-ISO or ST-PH) immediately after stroke (ST). Mice were sacrificed either at 3, 7 or 14 days after 60-minute right MCAO or sham surgery (n=4-6/group) and perilesional frontal cortex was isolated for miRNA analysis. Total RNA was isolated using either Qiagen miRNeasy® Mini Kit/ miRVANA miRNA isolation kit (Ambion, Life technologies). Whole miRNOme analysis of total RNA isolated from brain tissue was performed using miRCURY LNA TM Universal RT microRNA. Post-treatment with an ‘in vivo ready’ antagomir of miR-141-3p (7mg/kg i.v/day x 3 days; n=4/group) was given through lateral tail veins. Results: Using whole miRNOme analysis of approx. 800 miRNA, we found miR-141-3p was a unique miRNA whose expression was significantly upregulated in a time dependent manner up to day 14 after stroke. The post treatment with an ‘in vivo ready’ antogomir of miR-141-3p reduced the isolation-induced increase in miR-141-3p to levels almost equal to that of pair-housed controls. Post- treatment significantly reduced mortality (by 21% as compared to -ve control) and sensory motor deficits after stroke. mRNA targets analysis study using qPCR confirmed the significant (p<0.05 vs Neg Control ) upregulation of target several genes like arg-1, ccl22 and TGFbr1, markers of M2 type microglial activation, after antogomir treatment. Summary: The present data suggests the unique role of miR-141-3p in post stroke isolation. Temporal expression profiling studies suggest its validation as a potential targets. Post treatment data confirms the in vivo feasibility of miRNA modulation after stroke.

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. 

Post-stroke recovery updates

2018 ◽  
Vol 19 (1) ◽  
pp. 53-57
Author(s):  
Ana Maria Bumbea ◽  
Roxana Carmen Dumitraşcu ◽  
Bogdan Ştefan Bumbea ◽  
Anca Emanuela Muşetescu ◽  
Otilia Rogoveanu ◽  
...  
Keyword(s):  
Stroke Recovery ◽  
Post Stroke
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