scholarly journals Improved post-stroke spontaneous recovery by astrocytic extracellular vesicles

Author(s):  
Yessica Heras-Romero ◽  
Axayacatl Morales-Guadarrama ◽  
Ricardo Santana-Martínez ◽  
Isaac Ponce ◽  
Ruth Rincón-Heredia ◽  
...  
2021 ◽  
Author(s):  
Yessica Heras-Romero ◽  
Axayacatl Morales-Guadarrama ◽  
Ricardo Santana-Martínez ◽  
Isaac Ponce ◽  
Ruth Rincón-Heredia ◽  
...  

Spontaneous recovery after a stroke accounts for a major part of the neurological recovery in patients. However limited, the spontaneous recovery is mechanistically driven by axonal restorative processes for which several molecular cues have been previously described. We report the acceleration of spontaneous recovery in a preclinical model of ischemia/reperfusion in rats via a single intracerebroventricular administration of extracellular vesicles released from primary cortical astrocytes. We used MRI, confocal and multiphoton microscopy to correlate the structural remodeling of the corpus callosum and striatocortical circuits with neurological performance over 21 days. We also evaluated the functionality of the corpus callosum by repetitive recordings of compound action potentials to show that the recovery facilitated by astrocytic extracellular vesicles was both anatomical and functional. Our data provide compelling evidence that astrocytes can hasten the basal recovery that naturally occurs post-stroke through the release of cellular mediators contained in extracellular vesicles.


Brain ◽  
2020 ◽  
Vol 143 (6) ◽  
pp. 1857-1872 ◽  
Author(s):  
Elizabeth L Saionz ◽  
Duje Tadin ◽  
Michael D Melnick ◽  
Krystel R Huxlin

Abstract Stroke damage to the primary visual cortex (V1) causes a loss of vision known as hemianopia or cortically-induced blindness. While perimetric visual field improvements can occur spontaneously in the first few months post-stroke, by 6 months post-stroke, the deficit is considered chronic and permanent. Despite evidence from sensorimotor stroke showing that early injury responses heighten neuroplastic potential, to date, visual rehabilitation research has focused on patients with chronic cortically-induced blindness. Consequently, little is known about the functional properties of the post-stroke visual system in the subacute period, nor do we know if these properties can be harnessed to enhance visual recovery. Here, for the first time, we show that ‘conscious’ visual discrimination abilities are often preserved inside subacute, perimetrically-defined blind fields, but they disappear by ∼6 months post-stroke. Complementing this discovery, we now show that training initiated subacutely can recover global motion discrimination and integration, as well as luminance detection perimetry, just as it does in chronic cortically-induced blindness. However, subacute recovery was attained six times faster; it also generalized to deeper, untrained regions of the blind field, and to other (untrained) aspects of motion perception, preventing their degradation upon reaching the chronic period. In contrast, untrained subacutes exhibited spontaneous improvements in luminance detection perimetry, but spontaneous recovery of motion discriminations was never observed. Thus, in cortically-induced blindness, the early post-stroke period appears characterized by gradual—rather than sudden—loss of visual processing. Subacute training stops this degradation, and is far more efficient at eliciting recovery than identical training in the chronic period. Finally, spontaneous visual improvements in subacutes were restricted to luminance detection; discrimination abilities only recovered following deliberate training. Our findings suggest that after V1 damage, rather than waiting for vision to stabilize, early training interventions may be key to maximize the system’s potential for recovery.


2015 ◽  
Vol 4 (10) ◽  
pp. 1131-1143 ◽  
Author(s):  
Thorsten R. Doeppner ◽  
Josephine Herz ◽  
André Görgens ◽  
Jana Schlechter ◽  
Anna-Kristin Ludwig ◽  
...  

2019 ◽  
Author(s):  
Sana Smaoui ◽  
Denyse Richardson ◽  
Melanie Peladeau-Pigeon ◽  
Catriona Steele

Abstract Introduction For patients who have suffered a stroke, tongue strength may be decreased compared to healthy individuals. Patients with dysphagia following stroke are more likely to experience aspiration pneumonia, which has been associated with higher mortality rates and medical complications. Research on strengthening the tongue in the stroke population has shown positive effects of a tongue resistance training protocol. Research also suggests that swallow safety, or protection of the airway, may be improved as a result of such interventions, however the mechanism of improvement remains poorly understood, particularly whether improvement is attributed to the intervention alone, or to spontaneous recovery. This study aims to determine what aspects of the swallowing mechanism (response time, movement, etc. of different structures) are directly impacted in order to provide guidance to clinicians using such treatments.Methods and analysis A multi-site, assessor-blinded, randomized crossover trial was designed to determine the effects of a 4-week course of tongue pressure intervention supplemented with home practice in participants who experience dysphagia (PAS of 3 or greater) at baseline. An instrumental evaluation of swallowing (videofluoroscopic swallowing study) is utilized at baseline to determine whether swallowing safety is impaired. Additionally, a requirement for reduced tongue pressures (<40 kilopascals) on all three trials was added in order to target patients who would benefit from this training. Participants are randomized into a delayed treatment group or an immediate treatment group to control for the effects of spontaneous recovery. All participants receive the 4 week treatment consisting of 2 weekly sessions with a speech-language pathologist and complete daily homework plans. Videofluoroscopic swallowing studies are also performed pre and post intervention to quantify the degree of change attributed to the intervention. The study launched in May 2019 and will enroll a maximum of 40 participants.Discussion This study will explore the effects of tongue pressure intervention on swallowing parameters in patients presenting with dysphagia post-stroke. Describing how the intervention effects specific swallowing mechanisms will provide guidance to clinicians using such treatments with this population. Trial registration number ClinicalTrials.gov identifier NCT03969095, published May 31 2019; https://clinicaltrials.gov/ct2/show/NCT03969095?term=NCT03969095&rank=1


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Lisa F. Everton ◽  
Jacqueline K. Benfield ◽  
Emilia Michou ◽  
Shaheen Hamdy ◽  
Philip M. Bath

Swallowing impairment (dysphagia) post-stroke results in poorer outcomes. Pharyngeal electrical stimulation (PES) is a potential treatment for post-stroke dysphagia. In a post hoc analysis, we investigated PES using videofluoroscopy swallow studies (VFSS) from the STEPS trial incorporating multiple measures of safety (penetration aspiration scale-PAS), speed and duration (timing), and efficiency (clearance), as opposed to the original trial which only measured PAS scores. 81 randomised participants (PES ( N = 43 ) versus sham ( N = 38 )) were analysed at baseline and 2 weeks. Participants swallowed up to 6 × 5   ml and 1 × 50   ml of thin liquid barium at 40% w / v , images at ≥25 fps. Based on PAS, the 5 ml mode bolus (most frequently occurring PAS from 6 × 5   ml ) and the worst 50 ml bolus were chosen for further analysis. Eight timing measures were performed, including stage transition duration (STD) and pharyngeal transit time (PTT). Clearance measures comprised oral and pharyngeal residue and swallows to clear. Comparisons of change of scoring outcomes between PES and sham were done at 2 weeks. Wilcoxon Signed Ranks Test was also used to evaluate longitudinal changes from both groups’ combined results at two weeks. Between-group analysis showed no statistically significant differences. Issues with suboptimal image quality and frame rate acquisition affected final numbers. At two weeks, both groups demonstrated a significant improvement in most safety scores (PAS) and STD, possibly due to spontaneous recovery or a combination of spontaneous recovery and swallowing treatment and usual care. A nonsignificant trend for improvement was seen in other timing measures, including PTT. This study, which conducted additional measurements of kinematic and residue analysis on the STEPS data did not detect “missed” improvements in swallowing function that the PAS is not designed to measure. However, more studies with greater numbers are required.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Masaki Ito ◽  
Markus Aswendt ◽  
Michelle Y Cheng ◽  
Alex G Lee ◽  
Shunsuke Ishizaka ◽  
...  

Introduction: Spontaneous recovery after stroke occurs in both human and animals. However, the underlying molecular mechanisms driving spontaneous recovery are still unclear. This study investigates the molecular mechanisms driving spontaneous recovery after unilateral experimental stroke using RNA sequencing (RNAseq). Methods: Ischemic stroke was induced in C57BL/6J adult male mice by transient MCAO. Neurological score, vertical pole, and rotating horizontal beam test were performed at baseline and post stroke days (PD) 4, 8, and 14. All mice were sacrificed at PD15 and processed for immunohistochemistry or Hi-seq. Infarcts were visualized by T2WI at PD2 using 7T MR scanner or histology at PD15. All stroke mice included in the study have comparable cortico-striatal infarcts and exhibit similar prestroke baseline performance and PD4 deficits. These mice were further categorized into spontaneously recovered and non-recovered groups based on their rotating beam performance during recovery. Results: Out of 35 stroke mice with abovementioned similar conditions, 9 (26%) were categorized into spontaneously recovered group and 26 (74%) were categorized into non-recovered group. Hierarchical clustering analysis supported this categorization. At PD14, the spontaneously recovered group exhibited significant improvement in beam performance in distance traveled and speed (p<0.001). Using Ingenuity Pathway Analysis, the comparison of RNAseq transcriptome between ipsilesional and contralesional primary motor cortex (iM1 and cM1) in spontaneously recovered and non-recovered stroke mice revealed significant differential molecular pathways, including glutamate, calcium, and neurotrophin signaling pathways. Conclusions: Our study demonstrates that stroke mice with similar cortico-striatal infarct size can exhibit significant differences in their behavioral recovery outcome. The transcriptome profile in iM1-cM1 network at 2 weeks post-stroke highlighted several molecular pathways that were significantly different between spontaneously recovered and non-recovered mice. Validation of key molecular candidates from the RNAseq data would provide insights into the molecular mechanisms mediating spontaneous recovery after stroke.


2018 ◽  
Author(s):  
Belen Rubio Ballester ◽  
Armin Duff ◽  
Martina Maier ◽  
Monica Cameirao ◽  
Sergi Bermudez ◽  
...  

ABSTRACTThe impact of rehabilitation on post-stroke motor recovery and its dependency on the patient’s chronicity remain unclear. The existence and regularity of a, so called, proportional recovery rule across a range of functional deficits and therapies supports the notion that functional interventions have little or no impact beyond spontaneous recovery rates in a ‘critical window of recovery’ which lasts from 3 to 6 months post-stroke. In this meta-analysis, we apply a bootstrap analysis method to assess the overall impact of a specific VR-based rehabilitation protocol for the upper extremities on a homogeneous sample of 219 individuals with hemiparesis at various stages post stroke. Our analysis uncovers a precise gradient of sensitivity to treatment that expands more than one year beyond the limits of the so-called ‘critical window of recovery’. These findings redefine the limits of the so-called ‘critical window of recovery’ and suggest that stroke-derived plasticity mechanisms do facilitate functional recovery even at the chronic and late chronic stage.


2021 ◽  
Author(s):  
Tudor Popescu ◽  
Benjamin Stahl ◽  
Brenton M. Wiernik ◽  
Hannah Helm ◽  
Michaela Zemanek ◽  
...  

IMPORTANCE: Melodic Intonation Therapy (MIT) is a prominent rehabilitation programme for individuals with post-stroke aphasia. Despite substantial progress in recent years, the efficacy of MIT remains not fully understood. OBJECTIVE: Based on a-priori hypotheses, the present meta-analysis investigated the efficacy of MIT while considering quality of outcomes (psychometrically validated versus unvalidated measures), experimental design (presence versus absence of randomisation and control group), influence of spontaneous recovery (quantified as number of months post-stroke), MIT version applied (original versus modified protocol), and level of generalisation (performance on trained versus untrained items). DATA SOURCES: An extensive literature search in all major online databases, trials registers and the grey literature identified 606 studies (years searched: 1973-2021). STUDY SELECTION: Inclusion criteria: randomised controlled trial (RCT) data or case reports on adults with aphasia; pre-post assessment of language performance. Exclusion criteria: substantial variation from original MIT protocol; unvalidated outcomes, unless both trained and untrained items were compared; essential information not indicated/retrievable. Final sample: 22 studies. DATA EXTRACTION AND SYNTHESIS: Following PRISMA guidelines, studies were double-coded. Multi-level mixed- and random-effects models were used to separately meta-analyse RCT and non-RCT data. MAIN OUTCOMES AND MEASURES: Measures of language performance focused on aphasia severity, everyday communication ability, domain-general function, language comprehension, non-communicative language expression, and speech-motor planning. RESULTS: Unvalidated outcomes appeared to attenuate MIT's effect size by a factor of 0.29-0.43 across study designs when compared to validated outcomes. Moreover, MIT's effect size was 5.7 times larger for non-RCT data compared to RCT data. Effect size also decreased with number of months post-stroke, suggesting confound through spontaneous recovery primarily within the first year post-stroke. In contrast, variation of the original MIT protocol did not systematically alter benefit from treatment. Crucially, analyses demonstrated significantly improved performance on trained and untrained items. The latter finding arose mainly from gains in repetition tasks, rather than other domains of verbal expression including everyday communication ability. CONCLUSIONS AND RELEVANCE: Accounting for various methodological aspects, the current results confirm the promising role of MIT in improving language performance on trained items and in repetition tasks, while highlighting possible limitations in promoting everyday communication ability.


Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1226
Author(s):  
Mircea Popescu Driga ◽  
Bogdan Catalin ◽  
Denisa Greta Olaru ◽  
Agnieszka Slowik ◽  
Nikolaus Plesnila ◽  
...  

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.


Geriatrics ◽  
2019 ◽  
Vol 4 (3) ◽  
pp. 42 ◽  
Author(s):  
Viridiana Arreola ◽  
Natàlia Vilardell ◽  
Omar Ortega ◽  
Laia Rofes ◽  
Desiree Muriana ◽  
...  

Oropharyngeal dysphagia is a prevalent complication following stroke (PS-OD), and one that is sometimes spontaneously recovered. This study describes the natural history of PS-OD between admission and three months post-stroke, and the factors associated with its prevalence and development. PS-OD was assessed with the volume-viscosity swallow test (V-VST) in all stroke patients on admission and at the three-month follow-up. We analyzed clinical, demographic, and neuroanatomical factors of 247 older post-stroke patients (National Institute of Health Stroke Scale (NIHSS) = 3.5 ± 3.8), comparing among those with PS-OD the ones with and without spontaneous recovery. PS-OD prevalence on admission was 39.7% (34.0% impaired safety; 30.8%, efficacy) and 41.7% (19.4% impaired safety; 39.3%, efficacy) at three months. Spontaneous swallow recovery occurred in 42.4% of patients with unsafe and in 29.9% with ineffective swallow, associated with younger age and optimal functional status. However, 26% of post-stroke patients developed new signs/symptoms of ineffective swallow related to poor functional, nutritional and health status, and institutionalization. PS-OD prevalence on admission and at the three-month follow-up was very high in the study population. PS-OD is a dynamic condition with some spontaneous recovery in patients with optimal functional status, but also new signs/symptoms can appear due to poor functionality. Regular PS-OD monitoring is needed to identify patients at risk of nutritional and respiratory complications.


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