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Restoring brain function after stroke — bridging the gap between animals and humans

Key Points

  • Stroke is the leading cause of complex adult disability in the world, but currently we do not provide a sufficient dose of the right physical or behavioural interventions to drive recovery

  • Clear lesion-induced changes occur in brain structure and function early after stroke, which result in an environment with unique heightened plasticity that can support restoration of function, termed spontaneous biological recovery

  • Intense, high-dose behavioural training aimed at the reduction of impairment and the restoration of function should be (but currently is not) delivered in this critical time window

  • The basis of spontaneous biological recovery in humans is unclear, which yields uncertainty over how and when to augment or prolong this process with novel therapies — further characterization is required to enable realistic phase III trials

  • Human neuroimaging techniques combined with modelling approaches can provide the appropriate biomarkers with which to map out a mechanistic approach to understand who and when to treat

  • The use of structural imaging to quantify damage in a range of brain regions can help predict long-term outcomes and provide the basis for stratification in restorative trials

Abstract

Stroke is the leading cause of complex adult disability in the world. Recovery from stroke is often incomplete, which leaves many people dependent on others for their care. The improvement of long-term outcomes should, therefore, be a clinical and research priority. As a result of advances in our understanding of the biological mechanisms involved in recovery and repair after stroke, therapeutic opportunities to promote recovery through manipulation of poststroke plasticity have never been greater. This work has almost exclusively been carried out in preclinical animal models of stroke with little translation into human studies. The challenge ahead is to develop a mechanistic understanding of recovery from stroke in humans. Advances in neuroimaging techniques now enable us to reconcile behavioural accounts of recovery with molecular and cellular changes. Consequently, clinical trials can be designed in a stratified manner that takes into account when an intervention should be delivered and who is most likely to benefit. This approach is expected to lead to a substantial change in how restorative therapeutic strategies are delivered in patients after stroke.

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Figure 1: Proportional motor recovery in the upper limb.
Figure 2: Poststroke plasticity and recovery.
Figure 3: Characterization of anatomical damage.

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PowerPoint slides

Glossary

Impairment

Abnormality or loss of physiological or psychological body function or body structure

Biomarkers

Indicators of disease state that can be used clinically as a measure of underlying molecular or cellular processes that might be difficult to measure directly in humans, and can be used to predict recovery or treatment response.

Proportional recovery rule

The amount of function regained after stroke is a proportion of the initial deficit. For example, by 3 months, patients will regain 70% of the upper limb motor function that had been lost on day 3 after stroke.

Hemispatial neglect

Reduced awareness of stimuli on one side of space, even though sensory loss might be absent.

Spontaneous biological recovery

Recovery occurring in the first few weeks and months after stroke, attributable to increased poststroke plasticity mechanisms; recovery is rapid, occurs at the level of impairment and generalizes beyond the tasks that are used in poststroke training, compared with improvements seen in the chronic phase of stroke.

Neuronal oscillations

Rhythmic fluctuations in activity generated by neural tissue in the CNS either spontaneously or in response to stimuli; entrained oscillations in multiple neurons and neural networks are thought to form a critical interface between cellular activity and large-scale functions in the CNS.

Cortical microcircuits

Patterns of connections between specific excitatory and inhibitory neurons in the cortex.

Computational neurorehabilitation

A newly emerging field aimed at mathematical modelling of plasticity and learning to understand and improve recovery of individuals with neurological impairment.

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Ward, N. Restoring brain function after stroke — bridging the gap between animals and humans. Nat Rev Neurol 13, 244–255 (2017). https://doi.org/10.1038/nrneurol.2017.34

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