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Plasticity during stroke recovery: from synapse to behaviour

Key Points

  • Reductions in blood flow to the brain of sufficient duration and extent lead to stroke, which results in damage to neuronal networks and impairment of sensation, movement or cognition.

  • A time-limited window of neuroplasticity opens following stroke in the adult brain, during which partial behavioural recovery can occur. Neuroplasticity can be further augmented by rehabilitative therapy.

  • Enhanced sensory and motor performance that occur after stroke is referred to as recovery, although re-emergent post-stroke behaviour is unlikely to be identical to the pre-stroke state. A more accurate definition of recovery is behavioural compensation provided by remaining and newly developed brain circuits that results in altered and/or new response strategies.

  • Plasticity in the adult brain after stroke is enabled by a surprising amount of diffuse and redundant connectivity in the CNS and the ability of new structural and functional circuits to form through remapping between related cortical regions.

  • Many of the molecular mechanisms that underlie stroke recovery are identical to those involved in development. A 'critical period' of heightened neuroplasticity that is akin to that occurring during visual system development might exist after stroke. For successful rehabilitation after stroke it is crucial to align behavioural interventions with critical periods.

  • It is possible to conceptualize synaptic learning rules after stroke into two broad classes and temporal phases: first, homeostatic mechanisms ensure that each neuron receives an adequate amount of synaptic input akin to homeostatic plasticity; second, Hebbian mechanisms occur, during which synaptic strength is redistributed to favour coincident activity and properly functioning circuits.

Abstract

Reductions in blood flow to the brain of sufficient duration and extent lead to stroke, which results in damage to neuronal networks and the impairment of sensation, movement or cognition. Evidence from animal models suggests that a time-limited window of neuroplasticity opens following a stroke, during which the greatest gains in recovery occur. Plasticity mechanisms include activity-dependent rewiring and synapse strengthening. The challenge for improving stroke recovery is to understand how to optimally engage and modify surviving neuronal networks, to provide new response strategies that compensate for tissue lost to injury.

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Figure 1: Organization of the sensorimotor cortex and the relationship between synaptic circuit damage and local blood flow.
Figure 2: Enriched rehabilitation protocols and the critical period of post-stroke rehabilitation.
Figure 3: Time course and events associated with stroke recovery in the rodent peri-infarct zone.

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Acknowledgements

This work was supported by operating grants to T.H.M. and the In Vivo Imaging Centre from the Canadian Institutes of Health Research (CIHR) and a Grant in Aid from the Heart and Stroke Foundation of British Columbia and the Yukon. We thank C. Brown, K. Aminolterjari and I. Winship for helpful comments on a draft of this manuscript, and A. Siglerfor help with figure concepts. D.C. holds a Canada Research Chair in Stroke and Neuroplasticity and receives operating grants from CIHR and the Heart and Stroke Foundation of Ontario. T.H.M. and D.C. are recipients of a Vascular Cognitive Impairment team grant from the Canadian Stroke Network.

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Glossary

Recovery

The re-emergence of the exactmotor and sensory patterns that were in place before stroke. However, true recovery is rarely observed and most animal and human tests only assess performance changes, which typically are compensatory in nature.

Plasticity

Changes in the strength of synaptic connections in response to either an environmental stimulus or an alteration in synaptic activity in a network.

Behavioural compensation

The restoration of performance through the use of modified or alternative response strategies, such as relying on the unimpaired limb or incorporating postural changes (for example, shoulder and trunk rotations) to perform motor tasks.

Somatotopic

Organized by body parts, for example somatosensory cortex maps.

Motor cortex

The area of the cortex that is dedicated to controlling muscles.

Sensory cortex

The area of the cortex that is dedicated to processing sensation from various body parts.

Motor engram

A putative memory trace for a motor action or movement.

Remapping

The transfer of incoming sensory or motor output signals from one cortical region to another. This might not necessarily involve new structural circuits.

Ipsilateral pathways

Pathways that are present in the brain hemisphere or spinal cord on the same side as the body part to which they connect.

Infarct

The area that suffers a prolonged reduction in blood flow and undergoes sustained ischaemic depolarization during stroke. Most neurons and glia in this region will die.

Contralesional hemisphere

The hemisphere that is opposite to stroke damage. Contralateral pathways are those that are present in the brain hemisphere or spinal cord on the opposite side to a body part.

Lateralized activation

The degree to which sensory or motor pathways are crossed, for example the degree to which the left motor cortex controls the right limb.

Representation

An area of cortex dedicated to processing a sensation from a particular body part.

Penumbra

The area that is adjacent to the infarct and contains partial blood flow. Some neurons will survive in this area. The penumbra is also defined as the region of perfusion–diffusion mismatch by MRI imaging, in which blood flow might be reduced, although infarct-related diffusion signals have not yet been found.

Deafferentation

Loss of sensory activity.

Rewiring

Changes to the structure of neuronal axons or dendrites that might affect neuronal function.

Homeostatic plasticity

A negative feedback-mediated form of plasticity, also known as synaptic scaling, that serves to keep network activity at a desired set point. Homeostatic plasticity might be important after stroke for setting into motion pathways that restore synaptic activity.

Hebbian plasticity

A positive feedback-mediated form of plasticity in which synapses between presynaptic and postsynaptic neurons that are coincidently active are strengthened. Hebbian plasticity might be important after stroke for strengthening and retaining properly wired connections.

Ischaemia

Inadequate blood supply. The ischaemic core is the area with <20% blood flow during stroke, in which most neurons and glia will die.

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Murphy, T., Corbett, D. Plasticity during stroke recovery: from synapse to behaviour. Nat Rev Neurosci 10, 861–872 (2009). https://doi.org/10.1038/nrn2735

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