Abstract W P96: Optogenetic Neuronal Stimulation Enhances Neurotrophin Expression in the Contralesional Motor Cortex After Stroke

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Michelle Y Cheng ◽  
Eric H Wang ◽  
Corinne L Bart ◽  
Alex R Bautista ◽  
Wyatt J Woodson ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Functional Recovery ◽  
Primary Motor Cortex ◽  
Recovery Process ◽  
Cortical Reorganization ◽  
Stroke Recovery ◽  
Post Stroke ◽  
Neuronal Stimulation ◽  
Activity Dependent

Objective: Functional recovery after stroke has been observed and is currently attributed to both brain remodeling and plasticity. One form of cortical reorganization involves the balance of interhemispheric interactions between ipsilesional and contralesional cortex. Stimulation of ipsilesional primary motor cortex (iM1) has been shown to be beneficial, however, the role of the contralesional M1 (cM1) remains controversial. Recently we showed that optogenetic stimulations of iM1 post-stroke promote functional recovery. In this study, we investigate the role of contralesional cortex in recovery by optogenetically stimulating iM1 or cM1 and examine the involvement of activity-dependent neurotrophins. Methods: Thy-1-ChR2-YFP line-18 transgenic male mice were used. Mice underwent stereotaxic surgery to implant a fiber cannula in either iM1 or cM1, followed by an intraluminal middle cerebral artery suture occlusion. Optogenetic stimulation began at day5 post-stroke and continued until day14 post-stroke. Sensorimotor behavior tests were used to assess their recovery at day 0, 2, 7, 10 and 14 post-stroke. Mice were sacrificed at day15 post-stroke and neurotrophin expressions were examined using quantitative PCR. Results: Repeated iM1 stimulations promoted functional recovery at day14 post-stroke, with improved motor performance on the rotating beam test (p<0.01). Real-time PCR revealed significant increases of neurotrophin expressions in contralesional M1 at day15 post-stroke, including brain-derived neurotrophic factor (BDNF) (p<0.05), nerve growth factor (NGF) (p<0.05) and neurotrophin 3 (NTF3) (p<0.05). BDNF and NTF3 expression were also significantly increased in the contralesional S1 of stimulated mice (p<0.05). Conclusion: Our data suggest that activity-dependent neurotrophins in the contralesional cortex may be an important mechanism mediating stroke recovery. Current studies include specific stimulation and inhibition of the iM1 or cM1 post-stroke to elucidate the neurocircuitry mediating stroke recovery. In addition, the expression of neurotrophins will be examined in these studies to elucidate their role in the recovery process.

scholarly journals Cellular-resolution monitoring of ischemic stroke pathologies in the rat cortex

2021 ◽  
Author(s):  
Sergiy Chornyy ◽  
Aniruddha Das ◽  
Julie A Borovicka ◽  
Davina Patel ◽  
Hugh H Chan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Primary Motor Cortex ◽  
Activity Patterns ◽  
Recovery Process ◽  
Cortical Reorganization ◽  
Western World ◽  
Fluorescence Signal ◽  
Functional Changes ◽  
Post Stroke ◽  
Cortical Regions

Stroke is a leading cause of disability in the Western world. Current post-stroke rehabilitation treatments are only effective in approximately half of the patients. Therefore, there is a pressing clinical need for developing new rehabilitation approaches for enhancing the recovery process, which requires the use of appropriate animal models. Here we study the activity patterns of multiple cortical regions in the rat brain using two-photon microscopy. We longitudinally recorded the fluorescence signal from thousands of neurons labeled with a genetically-encoded calcium indicator before and after an ischemic stroke injury, and found substantial functional changes across motor, somatosensory, and visual cortical regions during the post-stroke cortical reorganization period. We show that a stroke injury in the primary motor cortex has an effect on the activity patterns of neurons not only in the motor and somatosensory cortices, but also in the more distant visual cortex, and that these changes include modified firing rates and kinetics of neuronal activity patterns in response to a sensory stimulus. Changes in neuronal population activity provided animal-specific, circuit-level information on the post-stroke cortical reorganization process, which may be essential for evaluating the efficacy of new approaches for enhancing the recovery process.

scholarly journals Post-stroke dendritic arbor regrowth – a cortical repair process requiring the actin nucleator Cobl

2021 ◽  
Author(s):  
Yuanyuan Ji ◽  
Dennis Koch ◽  
Jule González Delgado ◽  
Madlen Günther ◽  
Otto W. Witte ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Molecular Mechanisms ◽  
Primary Motor Cortex ◽  
Recovery Process ◽  
Repair Process ◽  
Artery Occlusion ◽  
Stroke Recovery ◽  
Dendritic Arbor ◽  
Post Stroke ◽  
Actin Nucleator

AbstractIschemic stroke is a major cause of death and long-term disability. We demonstrate that middle cerebral artery occlusion in mice leads to a strong decline in dendritic arborization of penumbral neurons. These defects were subsequently repaired by an ipsilateral recovery process requiring the actin nucleator Cobl. Ischemic stroke and excitotoxicity, caused by calpain-mediated proteolysis, significantly reduced Cobl levels. In an apparently unique manner among excitotoxicity-affected proteins, this Cobl decline was rapidly restored by increased mRNA expression and Cobl then played a pivotal role in post-stroke dendritic arbor repair in peri-infarct areas. In Cobl KO mice, the dendritic repair window determined to span day 2-4 post-stroke in WT strikingly passed without any dendritic regrowth. Instead, Cobl KO penumbral neurons of the primary motor cortex continued to show the dendritic impairments caused by stroke. Our results thereby highlight a powerful post-stroke recovery process and identified causal molecular mechanisms critical during post-stroke repair.

scholarly journals Progress in Clinical Neurosciences: Stroke Recovery and Rehabilitation

2006 ◽  
Vol 33 (4) ◽  
pp. 357-364 ◽  
Author(s):  
Robert Teasell ◽  
Nestor Bayona ◽  
Katherine Salter ◽  
Chelsea Hellings ◽  
Jamie Bitensky
Keyword(s):  
Cortical Reorganization ◽  
Stroke Recovery ◽  
Neurological Recovery ◽  
Complex Environments ◽  
Post Stroke ◽  
Brain Reorganization ◽  
Intact Cortex ◽  
The Individual ◽  
Insight Into

ABSTRACT:Background:Recent literature has provided new insights into the role of rehabilitation in neurological recovery post-stroke. The present review combines results of animal and clinical research to provide a summary of published information regarding the mechanisms of neural recovery and impact of rehabilitation.Methods:Plasticity of the uninjured and post-stroke brain is examined to provide a background for the examination of brain reorganization and recovery following stroke.Summary and Conclusions:Recent research has confirmed many of the basic underpinnings of rehabilitation and provided new insight into the role of rehabilitation in neurological recovery. Recovery post stroke is dependent upon cortical reorganization, and therefore, upon the presence of intact cortex, especially in areas adjacent to the infarct. Exposure to stimulating and complex environments and involvement in tasks or activities that are meaningful to the individual with stroke serves to increase cortical reorganization and enhance functional recovery. Additional factors associated with neurological recovery include size of stroke lesion, and the timing and intensity of therapy.

scholarly journals Effect of opposing needling on motor cortex excitability in healthy participants and in patients with post-stroke hemiplegia: study protocol for a single-blind, randomised controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mindong Xu ◽  
Yinyu Zi ◽  
Jianlu Wu ◽  
Nenggui Xu ◽  
Liming Lu ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Motor Evoked Potentials ◽  
Controlled Trial ◽  
Secondary Outcome ◽  
Post Stroke ◽  
Motor Cortex Excitability ◽  
Opposing Needling ◽  
Single Blind ◽  
Healthy Participants

Abstract Background Opposing needling has an obvious curative effect in the treatment of post-stroke hemiplegia; however, the mechanism of the opposing needling in the treatment of post-stroke hemiplegia is still not clear. The purpose of this study is to investigate the effect of opposing needling on the excitability of primary motor cortex (M1) of healthy participants and patients with post-stroke hemiplegia, which may provide insight into the mechanisms of opposing needling in treating post-stroke hemiplegia. Methods This will be a single-blind, randomised, sham-controlled trial in which 80 healthy participants and 40 patients with post-stroke hemiplegia will be recruited. Healthy participants will be randomised 1:1:1:1 to the 2-Hz, 50-Hz, 100-Hz, and sham electroacupuncture groups. Patients with post-stroke hemiplegia will be randomised 1:1 to the opposing needling or conventional treatment groups. The M1 will be located in all groups by using neuroimaging-based navigation. The stimulator coil of transcranial magnetic stimulation (TMS) will be moved over the left and right M1 in order to identify the TMS hotspot, followed by a recording of resting motor thresholds (RMTs) and motor-evoked potentials (MEPs) of the thenar muscles induced by TMS before and after the intervention. The primary outcome measure will be the percent change in the RMTs of the thenar muscles at baseline and after the intervention. The secondary outcome measures will be the amplitude (μV) and latency (ms) of the MEPs of the thenar muscles at baseline and after the intervention. Discussion The aim of this trial is to explore the effect of opposing needling on the excitability of M1 of healthy participants and patients with post-stroke hemiplegia. Trial registration Chinese Clinical Trial Registry ChiCTR1900028138. Registered on 13 December 2019.

Reversal of Cortical Reorganization in Human Primary Motor Cortex Following Thumb Reconstruction

2010 ◽  
Vol 103 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Zhen Ni ◽  
Dimitri J. Anastakis ◽  
Carolyn Gunraj ◽  
Robert Chen
Keyword(s):  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Short Interval ◽  
Body Part ◽  
Cortical Reorganization ◽  
Traumatic Amputation ◽  
Motor Threshold ◽  
Thumb Reconstruction ◽  
Intact Side ◽  
Injured Side

Deafferentation such as the amputation of a body part causes cortical reorganization in the primary motor cortex (M1). We investigated whether this reorganization is reversible after reconstruction of the lost body part. We tested two patients who had long-standing thumb amputations followed by thumb reconstruction with toe-to-thumb transfer 9 to 10 mo later and one patient who underwent thumb replantation immediately following traumatic amputation. Using transcranial magnetic stimulation, we measured the motor evoked potential (MEP) threshold, latency, short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) at different time points in the course of recovery in abductor pollicis brevis muscle. For the two patients who underwent late toe-to-thumb transfer, the rest motor threshold was lower on the injured side than that on the intact side before surgery and it increased with time after reconstruction, whereas the active motor threshold remained unchanged. The rest and active MEP latencies were similar on the injured side before and ≤15 wk after surgery and followed by restoration of expected latency differences. SICI was reduced before surgery and progressively normalized with the time after surgery. ICF did not change with time. These physiological measures correlated with the recovery of motor and sensory functions. All the measurements on the intact side of the toe-to-thumb transfer patients and in the patient with thumb replantation immediately following traumatic amputation remained stable over time. We conclude that chronic reorganization occurring in the M1 after amputation can be reversed by reconstruction of the lost body part.

scholarly journals Role of cutaneous and proprioceptive inputs in sensorimotor integration and plasticity occurring in the facial primary motor cortex

2020 ◽  
Vol 598 (4) ◽  
pp. 839-851 ◽  
Author(s):  
Giovanna Pilurzi ◽  
Francesca Ginatempo ◽  
Beniamina Mercante ◽  
Luigi Cattaneo ◽  
Giovanni Pavesi ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Sensorimotor Integration ◽  
Primary Motor Cortex ◽  
Proprioceptive Inputs

scholarly journals Brain stimulation for arm recovery after stroke (B-STARS): protocol for a randomised controlled trial in subacute stroke patients

BMJ Open ◽  
2017 ◽  
Vol 7 (8) ◽  
pp. e016566
Author(s):  
Eline C C van Lieshout ◽  
Johanna M A Visser-Meily ◽  
Sebastiaan F W Neggers ◽  
H Bart van der Worp ◽  
Rick M Dijkhuizen
Keyword(s):  
Motor Cortex ◽  
Upper Limb ◽  
Brain Stimulation ◽  
Primary Outcome ◽  
Primary Motor Cortex ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Stroke Patients ◽  
Post Stroke ◽  
Subacute Stroke

IntroductionMany patients with stroke have moderate to severe long-term sensorimotor impairments, often including inability to execute movements of the affected arm or hand. Limited recovery from stroke may be partly caused by imbalanced interaction between the cerebral hemispheres, with reduced excitability of the ipsilesional motor cortex while excitability of the contralesional motor cortex is increased. Non-invasive brain stimulation with inhibitory repetitive transcranial magnetic stimulation (rTMS) of the contralesional hemisphere may aid in relieving a post-stroke interhemispheric excitability imbalance, which could improve functional recovery. There are encouraging effects of theta burst stimulation (TBS), a form of TMS, in patients with chronic stroke, but evidence on efficacy and long-term effects on arm function of contralesional TBS in patients with subacute hemiparetic stroke is lacking.Methods and analysisIn a randomised clinical trial, we will assign 60 patients with a first-ever ischaemic stroke in the previous 7–14 days and a persistent paresis of one arm to 10 sessions of real stimulation with TBS of the contralesional primary motor cortex or to sham stimulation over a period of 2 weeks. Both types of stimulation will be followed by upper limb training. A subset of patients will undergo five MRI sessions to assess post-stroke brain reorganisation. The primary outcome measure will be the upper limb function score, assessed from grasp, grip, pinch and gross movements in the action research arm test, measured at 3 months after stroke. Patients will be blinded to treatment allocation. The primary outcome at 3 months will also be assessed in a blinded fashion.Ethics and disseminationThe study has been approved by the Medical Research Ethics Committee of the University Medical Center Utrecht, The Netherlands. The results will be disseminated through (open access) peer-reviewed publications, networks of scientists, professionals and the public, and presented at conferences.Trial registration numberNTR6133

First-stroke recovery process: The role of family social support

2000 ◽  
Vol 81 (7) ◽  
pp. 881-887 ◽  
Author(s):  
Evie Tsouna-Hadjis ◽  
Kostas N. Vemmos ◽  
Nikolaos Zakopoulos ◽  
Stamatis Stamatelopoulos
Keyword(s):  
Social Support ◽  
Recovery Process ◽  
Stroke Recovery ◽  
Family Social Support
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