Enhanced Spontaneous Motor Recovery After Stroke in Mice Treated With Cerebrolysin

2021 ◽  
pp. 154596832110007
Author(s):  
Scott R. DeBoer ◽  
Robert Hubbard ◽  
Mahlet Mersha ◽  
Gabriel Pinilla Monsalve ◽  
Stefan Winter ◽  
...  
Keyword(s):  
Spontaneous Recovery ◽  
Complete Recovery ◽  
Motor Recovery ◽  
Sensitive Period ◽  
Rodent Models ◽  
Repair Mechanisms ◽  
Stroke Models ◽  
Photothrombotic Stroke ◽  
And Training ◽  
Recovery Of Motor Function

Background Motor recovery after stroke in humans and in rodent models is time sensitive. Recovery in patients is a result of biological spontaneous recovery via endogenous repair mechanisms and is likely improved by enhancing the synaptic plasticity required for endogenous repair. Cerebrolysin is a polypeptide preparation known to enhance neuroplasticity and may improve recovery in patients. In mice, we tested the hypothesis that Cerebrolysin can act poststroke to enhance both spontaneous and training-associated motor recovery. Methods Mice were trained to perform a skilled prehension task. We then induced a photothrombotic stroke in the caudal forelimb area, after which we retrained animals on the prehension task in the presence or absence of Cerebrolysin after a 2-day or 8-day delay. Mice received daily intraperitoneal Cerebrolysin or saline injections starting poststroke day 1 or poststroke day 7. Results Prior studies showed that poststroke recovery of prehension can occur if animals receive rehabilitative training during an early sensitive period but is incomplete if rehabilitative training is delayed. In contrast, we show complete recovery of prehension, despite a delay in rehabilitative training, when mice receive daily Cerebrolysin administration starting on poststroke day 1 or on poststroke day 8. When Cerebrolysin is given on poststroke day 1, recovery occurred even in the absence of training. Stroke volumes were similar across groups. Conclusions Poststroke Cerebrolysin administration leads to recovery of motor function independent of rehabilitative training without a protective effect on stroke volume. This is one of the first demonstrations of training-independent motor recovery in rodent stroke models.

scholarly journals Characterizing Spontaneous Motor Recovery Following Cortical and Subcortical Stroke in the Rat

2018 ◽  
Vol 33 (1) ◽  
pp. 27-37 ◽  
Author(s):  
Sudhir Karthikeyan ◽  
Matthew Strider Jeffers ◽  
Anthony Carter ◽  
Dale Corbett
Keyword(s):  
Outcome Measures ◽  
Spontaneous Recovery ◽  
Motor Recovery ◽  
Clinical Population ◽  
Lesion Volume ◽  
Sprague Dawley ◽  
Motor Impairments ◽  
Preclinical Research ◽  
Stroke Models ◽  
Human Stroke

Background. Stroke is a leading cause of neurological disability, often resulting in long-term motor impairments due to damage to cortical or subcortical motor areas. Despite the high prevalence of subcortical strokes in the clinical population, preclinical research has primarily focused on investigating and treating cortical strokes. Moreover, while both humans and animals show spontaneous recovery following stroke, little is known about how injury location affects this process. Objective. To capture the heterogeneity of human stroke and examine how stroke location affects spontaneous motor recovery following damage to cortical, subcortical, or a combination of both areas. Methods. Endothelin-1 (ET-1), a potent vasoconstrictor, was used to produce focal infarcts in the forelimb motor cortex (FMC), the dorsolateral striatum (DLS) or both the FMC and DLS in male Sprague-Dawley rats. The spontaneous recovery profile of animals was followed over an 8-week period using a battery of behavioral tasks assessing motor function and limb preference. Results. All 3 groups showed significant impairments on the Montoya staircase, beam, and cylinder tests following stroke, with the combined group (FMC + DLS) having the largest and most persistent impairments. Importantly, spontaneous recovery was not simply dependent on lesion volume, but on location, and the behavioral test employed. Conclusions. Stroke location markedly and differentially influences the level of spontaneous functional recovery, which is only captured by using multiple outcome measures. These results illustrate the need for preclinical stroke models to align with the heterogeneity of human stroke, especially with respect to lesion location, size, and outcome measures.

Abstract TP131: SNRI Atomoxetine and SSRI Fluoxetine Promote Motor Recovery After Photothrombotic Stroke in Mice

Stroke ◽  
2019 ◽  
Vol 50 (Suppl_1) ◽  
Author(s):  
Faisal F Alamri ◽  
Abdullah Al Shoyaib ◽  
Anisha Paul ◽  
Srinidhi Jayaraman ◽  
Thiruma V Arumugam ◽  
...  
Keyword(s):  
Motor Recovery ◽  
Photothrombotic Stroke

scholarly journals Critical Period After Stroke Study (CPASS): A phase II clinical trial testing an optimal time for motor recovery after stroke in humans

2021 ◽  
Vol 118 (39) ◽  
pp. e2026676118
Author(s):  
Alexander W. Dromerick ◽  
Shashwati Geed ◽  
Jessica Barth ◽  
Kathaleen Brady ◽  
Margot L. Giannetti ◽  
...  
Keyword(s):  
Human Brain ◽  
Controlled Trial ◽  
Primary Outcome Measure ◽  
Essential Elements ◽  
Motor Recovery ◽  
Stroke Recovery ◽  
Sensitive Period ◽  
Optimal Time ◽  
Motor Training ◽  
Acute Group

Restoration of human brain function after injury is a signal challenge for translational neuroscience. Rodent stroke recovery studies identify an optimal or sensitive period for intensive motor training after stroke: near-full recovery is attained if task-specific motor training occurs during this sensitive window. We extended these findings to adult humans with stroke in a randomized controlled trial applying the essential elements of rodent motor training paradigms to humans. Stroke patients were adaptively randomized to begin 20 extra hours of self-selected, task-specific motor therapy at ≤30 d (acute), 2 to 3 mo (subacute), or ≥6 mo (chronic) after stroke, compared with controls receiving standard motor rehabilitation. Upper extremity (UE) impairment assessed by the Action Research Arm Test (ARAT) was measured at up to five time points. The primary outcome measure was ARAT recovery over 1 y after stroke. By 1 y we found significantly increased UE motor function in the subacute group compared with controls (ARAT difference = +6.87 ± 2.63,P= 0.009). The acute group compared with controls showed smaller but significant improvement (ARAT difference = +5.25 ± 2.59 points,P= 0.043). The chronic group showed no significant improvement compared with controls (ARAT = +2.41 ± 2.25,P= 0.29). Thus task-specific motor intervention was most effective within the first 2 to 3 mo after stroke. The similarity to rodent model treatment outcomes suggests that other rodent findings may be translatable to human brain recovery. These results provide empirical evidence of a sensitive period for motor recovery in humans.

CONSTRAINT INDUCED MOVEMENT THERAPY FOR MOTOR RECOVERY IN CHRONIC STROKE PATIENT IN RURAL INDIA

2020 ◽  
Vol 4 (5) ◽  
Author(s):  
Anchit Gugnani
Keyword(s):  
Positive Reinforcement ◽  
Spontaneous Recovery ◽  
Recovery Of Function ◽  
Motor Recovery ◽  
Rural India ◽  
Motor Deficits ◽  
Stroke Patients ◽  
Constraint Induced Movement Therapy ◽  
Recovery Stroke ◽  
Do So

A possible explanation for the substantial remaining motor deficits in stroke patients might be the occurrence of learned nonuse, a phenomenon first described by Taub. Stroke patients who initially attempt to use the affected extremity find themselves unable to do so because the process of spontaneous recovery of function has not yet proceeded sufficiently far. This results in the experience of failure or punishment for attempts to move the extremity and in positive reinforcement for compensatory movements by the unaffected extremity-a learning process that might be supported by the teaching of compensatory activity during rehabilitation. Keywords: CIMT, Motor recovery, Stroke patients

scholarly journals Longitudinal Assessment of Motor Recovery of Contralateral Hand after Basal Ganglia Infarction Using Functional Magnetic Resonance Imaging

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Yue Fu ◽  
Quan Zhang ◽  
Chunshui Yu ◽  
Jing Zhang ◽  
Ning Wang ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Motor Function ◽  
Acute Phase ◽  
Block Design ◽  
Chronic Phase ◽  
Motor Recovery ◽  
Activation Domain ◽  
Functional Rehabilitation ◽  
Time Points ◽  
Recovery Of Motor Function

We used functional fMRI to study the brain activation during active finger movements at different time points during the recovery phase following basal ganglia infarction. Four hemiplegic patients with basal ganglia infarction were serially evaluated at different time points spanning the acute and chronic phase using fMRI. To evaluate motor recovery, the patients were asked to perform functional tasks arranged in a block design manner with their hand. On follow-up (chronic phase), three patients achieved significant recovery of motor function of affected limbs. Activation of bilateral sensorimotor cortex (SMC) was observed in two of these patients, while activation of cerebellum was observed in all patients. No remarkable recovery of motor function was noted in one patient with left basal ganglia infarction. In this patient, the activation domain was located in SMC of both sides in acute phase and in ipsilateral SMC in chronic phase. Contralateral SMC appears to be involved in the functional rehabilitation following basal ganglia infarction. The cerebellum may act as an intermediary during functional recovery following basal ganglia infarction. The activation domain associated with active finger movement may be bilateral in acute phase; one patient was ipsilateral in the chronic stage.

scholarly journals Design and Evaluation of a Robotic Device for Automated Tail Vein Cannulations in Rodent Models

2017 ◽  
Vol 11 (4) ◽  
Author(s):  
Alex Fromholtz ◽  
Max L. Balter ◽  
Alvin I. Chen ◽  
Josh M. Leipheimer ◽  
Anil Shrirao ◽  
...  
Keyword(s):  
Degrees Of Freedom ◽  
Near Infrared ◽  
Three Dimensional ◽  
Needle Insertion ◽  
Rodent Models ◽  
Tail Vein ◽  
Work Volume ◽  
Stereo Cameras ◽  
And Training ◽  
Three Degrees Of Freedom

Preclinical testing in rodent models is a ubiquitous part of modern biomedical research and commonly involves accessing the venous bloodstream for blood sampling and drug delivery. Manual tail vein cannulation is a time-consuming process and requires significant skill and training, particularly since improperly inserted needles can affect the experimental results and study outcomes. In this paper, we present a miniaturized, robotic medical device for automated, image-guided tail vein cannulations in rodent models. The device is composed of an actuated three degrees-of-freedom (DOFs) needle manipulator, three-dimensional (3D) near-infrared (NIR) stereo cameras, and an animal holding platform. Evaluating the system through a series of workspace simulations and free-space positioning tests, the device exhibited a sufficient work volume for the needle insertion task and submillimeter accuracy over the calibration targets. The results indicate that the device is capable of cannulating tail veins in rodent models as small as 0.3 mm in diameter, the smallest diameter vein required to target.

scholarly journals Boosting generalized recovery by combined optogenetic stimulation and training after stroke

2020 ◽  
Author(s):  
Emilia Conti ◽  
Anna Letizia Allegra Mascaro ◽  
Alessandro Scaglione ◽  
Giuseppe de Vito ◽  
Francesco Calugi ◽  
...  
Keyword(s):  
Cortical Excitability ◽  
Functional Restoration ◽  
Cortical Activation ◽  
Motor Training ◽  
Ischemic Event ◽  
Optogenetic Stimulation ◽  
Repetitive Motor ◽  
And Training ◽  
Recovery Of Motor Function ◽  
Stimulation Of

AbstractAn ischemic event is followed by extensive changes in cortical excitability involving both hemispheres. Plasticity in the injured hemisphere plays a crucial role in poststroke motor recovery and it is a primary target for rehabilitation therapy. Though stimulation of the ipsilesional motor cortex, especially when paired with motor training, facilitates plasticity and functional restoration, the mechanisms underneath the reshaping of cortical functionality are widely unknown. Here, we designed a protocol of optogenetic stimulation of the peri-infarct region as a neuro-plasticizing treatment coupled with a repetitive motor training. This treatment promoted a generalized recovery in forelimb function and the rescue of the essential features of cortical activation profiles during the execution of the motor training. The present work, by exploiting different approaches, provides a fundamental means to better understand the mechanisms underlying the recovery of motor function.

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