scholarly journals Micro RNA 181c-5p: A promising target for post-stroke recovery in socially isolated mice

2020 ◽  
Vol 715 ◽  
pp. 134610 ◽  
Author(s):  
Maria Antony ◽  
Victoria Scranton ◽  
Pranay Srivastava ◽  
Rajkumar Verma
Keyword(s):  
Micro Rna ◽  
Stroke Recovery ◽  
Post Stroke ◽  
Promising Target ◽  
Socially Isolated

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.

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

LncRNAs a New Target for Post-Stroke Recovery

2020 ◽  
Vol 26 (26) ◽  
pp. 3115-3121
Author(s):  
Jun Yang ◽  
Jingjing Zhao ◽  
Xu Liu ◽  
Ruixia Zhu
Keyword(s):  
Ischemic Stroke ◽  
Microglial Activation ◽  
Vital Role ◽  
Stroke Recovery ◽  
Biological Processes ◽  
Current Development ◽  
Post Stroke ◽  
Cascade Processes ◽  
Non Coding Rnas ◽  
Neuron Injury

LncRNAs (long non-coding RNAs) are endogenous molecules, involved in complicated biological processes. Increasing evidence has shown that lncRNAs play a vital role in the post-stroke pathophysiology. Furthermore, several lncRNAs were reported to mediate ischemia cascade processes include apoptosis, bloodbrain barier breakdown, angiogenesis, microglial activation induced neuroinflammation which can cause neuron injury and influence neuron recovery after ischemic stroke. In our study, we first summarize current development about lncRNAs and post-stroke, focus on the regulatory roles of lncRNAs on pathophysiology after stroke. We also reviewed genetic variation in lncRNA associated with functional outcome after ischemic stroke. Additionally, lncRNA-based therapeutics offer promising strategies to decrease brain damage and promote neurological recovery following ischemic stroke. We believe that lncRNAs will become promising for the frontier strategies for IS and can open up a new path for the treatment of IS in the future.

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 Rehabilitation strategy for post-stroke recovery using an innovative elbow exoskeleton

2019 ◽  
Vol 233 (6) ◽  
pp. 668-680 ◽  
Author(s):  
Soumya K Manna ◽  
Venketesh N Dubey
Keyword(s):  
Acute Stage ◽  
Joint Torque ◽  
Stroke Recovery ◽  
Structural Description ◽  
Post Stroke ◽  
Single Structure ◽  
Rate Of Recovery ◽  
Last Stage ◽  
Working Region ◽  
Rehabilitation Strategy

Intensive and adaptive rehabilitation therapy is beneficial for post-stroke recovery. Three modes of rehabilitation are generally performed at different stages after stroke: external force-based control in the acute stage, assistive force-based rehabilitation in the midway of recovery and resistive force-based rehabilitation in the last stage. To achieve the above requirements, an innovative elbow exoskeleton has been developed to incorporate the three modes of rehabilitation in a single structure. The structure of the exoskeleton has been designed in such a way that the whole working region is divided into three where each region can provide a different mode of rehabilitation. Recovery rate can be varied for individuals since it depends on various parameters. To evaluate the rate of recovery, three joint parameters have been identified: range of angular movement, angular velocity and joint torque. These parameters are incorporated into the framework of planning a novel rehabilitation strategy, which is discussed in this article along with the structural description of the designed exoskeleton.

Abstract W MP41: Potentiation of Gaba-Mediated Synaptic Inhibition in the Recovery Phase: A Novel Therapeutic Target for Stroke

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Takeshi Hiu ◽  
Tonya Bliss ◽  
Jeanne Paz ◽  
Eric Wang ◽  
Zoya Farzampour ◽  
...  
Keyword(s):  
Pyramidal Cells ◽  
Recovery Phase ◽  
Synaptic Activity ◽  
Stroke Recovery ◽  
Functional Changes ◽  
Post Stroke ◽  
Array Tomography ◽  
Neuronal Inhibition ◽  
Gaba Signaling ◽  
Novel Therapeutic

Background: Stroke is a major cause of disability yet pharmacotherapy targeting the recovery phase is lacking. Cortical circuit reorganization adjacent to the stroke site promotes recovery, thus elucidating mechanisms that promote this plasticity could lead to new therapeutics. Tonic neuronal inhibition, mediated by extrasynaptic GABA A receptors,inhibits post-stroke recovery. However, effects of phasic (synaptic) GABA signaling - which promotes plasticity during development - are unknown. Here we use a combined approach of i) array tomography to determine the composition of GABA synapses in the post-stroke mouse brain, ii) electrophysiology to determine whether stroke leads to functional changes in GABA-mediated phasic inhibition, and (iii) treatment with zolpidem, an FDA-approved GABA agonist, to modulate recovery. Results: We found, using array tomography, a 1.7-fold increase in the number of GABAergic synapses containing the α1 receptor subunit in layer 5 of the peri-infarct cortex (synapse number/μm 3 : 0.039±0.006 (control) vs 0.064±0.006 (stroke); P<0.01), but not in layer 2/3. There was an associated increase in spontaneous inhibitory post-synaptic currents (sIPSC) specific to layer 5 pyramidal neurons (sIPSC charge (fC): -403±27.8 (control) vs -724±166 (stroke); p=0.03). This effect was transient, occurring during the onset of functional recovery. To test whether the increased phasic inhibitory GABAergic signaling promotes stroke recovery, we treated animals with zolpidem, an agonist with high affinity for α1 subunit-containing GABA A receptors. Low dose zolpidem increased GABA A phasic signaling in layer 5 pyramidal cells and notably increased the rate and extent of behavioral recovery without altering infarct size. Conclusions: These data provide the first evidence that enhanced GABA A -mediated synaptic activity during the recovery phase improves stroke outcome. These data identify modulation of phasic GABA signaling as a novel therapeutic strategy for stroke, indicate zolpidem as a potential drug to improve recovery, and underscore the necessity to distinguish the role of tonic and phasic GABA inhibition in stroke recovery.

MLC901 in subacute post-stroke recovery in the eastern European population: Preliminary results of a multicentre study

2021 ◽  
Vol 429 ◽  
pp. 119651
Author(s):  
Anita Anisovska ◽  
Mariusz Janta ◽  
Anna Tomašová ◽  
Slavomír Guťan ◽  
Barbora Garajová ◽  
...  
Keyword(s):  
Multicentre Study ◽  
European Population ◽  
Stroke Recovery ◽  
Eastern European ◽  
Preliminary Results ◽  
Post Stroke

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.

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