Enhancing the alignment of the preclinical and clinical stroke recovery research pipeline: Consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable translational working group

Corbett, Dale; Carmichael, S. Thomas; Murphy, Timothy H.; Jones, Theresa A.; Schwab, Martin E.; Jolkkonen, Jukka; Clarkson, Andrew N.; Dancause, Numa; Wieloch, Tadeusz; Johansen‐Berg, Heidi; Nilsson, Michael; McCullough, Louise D.; Joy, Mary

doi:10.1177/1747493017711814

Cited by 95 publications

(105 citation statements)

References 72 publications

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“…Despite some differences in anatomy and central nervous system organization, stroke in rats results in abnormalities in muscle coordination similar to those observed in humans 5 , 41 , 44 , furthering the construct validity of using rats to study stroke impairment and recovery. International guidelines recommend using comparable preclinical and clinical outcome measures to minimize the potential of translational failure 20 , 60 . The present study demonstrates the feasibility of using kinematic analysis to align the methodology of impairment measurement between preclinical and clinical stroke studies.…”

Section: Discussionmentioning

confidence: 99%

Post-stroke kinematic analysis in rats reveals similar reaching abnormalities as humans

Balbinot

Schuch

Jeffers

et al. 2018

Sci Rep

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A coordinated pattern of multi-muscle activation is essential to produce efficient reaching trajectories. Disruption of these coordinated activation patterns, termed synergies, is evident following stroke and results in reaching deficits; however, preclinical investigation of this phenomenon has been largely ignored. Furthermore, traditional outcome measures of post-stroke performance seldom distinguish between impairment restitution and compensatory movement strategies. We sought to address this by using kinematic analysis to characterize reaching movements and kinematic synergies of rats performing the Montoya staircase task, before and after ischemic stroke. Synergy was defined as the simultaneous movement of the wrist and other proximal forelimb joints (i.e. shoulder, elbow) during reaching. Following stroke, rats exhibited less individuation between joints, moving the affected limb more as a unit. Moreover, abnormal flexor synergy characterized by concurrent elbow flexion, shoulder adduction, and external rotation was evident. These abnormalities ultimately led to inefficient and unstable reaching trajectories, and decreased reaching performance (pellets retrieved). The observed reaching abnormalities in this preclinical stroke model are similar to those classically observed in humans. This highlights the potential of kinematic analysis to better align preclinical and clinical outcome measures, which is essential for developing future rehabilitation strategies following stroke.

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Section: Discussionmentioning

confidence: 99%

Post-stroke kinematic analysis in rats reveals similar reaching abnormalities as humans

Balbinot

Schuch

Jeffers

et al. 2018

Sci Rep

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“…We hope that researchers, clinicians and academics working or interested in the field of stroke recovery, together with funding bodies and journal editors, will join us in pursuing and promoting the goals outlined here and in our recommendation papers. [2][3][4][5] Francesca Bosetti, Marian C Brady, Leeanne M Carey,…”

Section: The Way Forwardmentioning

confidence: 99%

Agreed definitions and a shared vision for new standards in stroke recovery research: The Stroke Recovery and Rehabilitation Roundtable taskforce

Bernhardt

Hayward

Kwakkel

et al. 2017

International Journal of Stroke

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The first Stroke Recovery and Rehabilitation Roundtable established a game changing set of new standards for stroke recovery research. Common language and definitions were required to develop an agreed framework spanning the four working groups: translation of basic science, biomarkers of stroke recovery, measurement in clinical trials and intervention development and reporting. This paper outlines the working definitions established by our group and an agreed vision for accelerating progress in stroke recovery research.

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“…In the context of stroke recovery, it is important to recognize that EE needs to include a task specific component that targets the animals’ primary deficits. For example, upper limb impairment is very common clinically (Duncan et al, 1992 ; Kwakkel et al, 2003 ) and consequently, most preclinical investigators target the forelimb motor cortex in their stroke studies (Murphy and Corbett, 2009 ; Corbett et al, 2017 ). EE alone is not effective in promoting recovery of skilled forelimb movements (e.g., reaching; Grabowski et al, 1993 ), since there is no opportunity to engage in this activity in standard EE configurations.…”

Section: Early Beginningsmentioning

confidence: 99%

Is Environmental Enrichment Ready for Clinical Application in Human Post-stroke Rehabilitation?

McDonald

Hayward

Rosbergen

et al. 2018

Front. Behav. Neurosci.

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Environmental enrichment (EE) has been widely used as a means to enhance brain plasticity mechanisms (e.g., increased dendritic branching, synaptogenesis, etc.) and improve behavioral function in both normal and brain-damaged animals. In spite of the demonstrated efficacy of EE for enhancing brain plasticity, it has largely remained a laboratory phenomenon with little translation to the clinical setting. Impediments to the implementation of enrichment as an intervention for human stroke rehabilitation and a lack of clinical translation can be attributed to a number of factors not limited to: (i) concerns that EE is actually the “normal state” for animals, whereas standard housing is a form of impoverishment; (ii) difficulty in standardizing EE conditions across clinical sites; (iii) the exact mechanisms underlying the beneficial actions of enrichment are largely correlative in nature; (iv) a lack of knowledge concerning what aspects of enrichment (e.g., exercise, socialization, cognitive stimulation) represent the critical or active ingredients for enhancing brain plasticity; and (v) the required “dose” of enrichment is unknown, since most laboratory studies employ continuous periods of enrichment, a condition that most clinicians view as impractical. In this review article, we summarize preclinical stroke recovery studies that have successfully utilized EE to promote functional recovery and highlight the potential underlying mechanisms. Subsequently, we discuss how EE is being applied in a clinical setting and address differences in preclinical and clinical EE work to date. It is argued that the best way forward is through the careful alignment of preclinical and clinical rehabilitation research. A combination of both approaches will allow research to fully address gaps in knowledge and facilitate the implementation of EE to the clinical setting.

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Enhancing the alignment of the preclinical and clinical stroke recovery research pipeline: Consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable translational working group

Abstract: Stroke recovery research involves distinct biological and clinical targets compared to the study of acute stroke. Guidelines are proposed for the pre-clinical modeling of stroke recovery and for the alignment of pre-clinical studies to clinical trials in stroke recovery.

Cited by 95 publications

References 72 publications

Post-stroke kinematic analysis in rats reveals similar reaching abnormalities as humans

Post-stroke kinematic analysis in rats reveals similar reaching abnormalities as humans

Agreed definitions and a shared vision for new standards in stroke recovery research: The Stroke Recovery and Rehabilitation Roundtable taskforce

Is Environmental Enrichment Ready for Clinical Application in Human Post-stroke Rehabilitation?

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