Finding an optimal rehabilitation paradigm after stroke: enhancing fiber growth and training of the brain at the right moment

Once again proving no need for a doctor in stroke recovery. 

Finding an optimal rehabilitation paradigm after stroke: enhancing fiber growth and training of the brain at the right moment

Anna-Sophia Wahl^1,2* and Martin E. Schwab^1,2

• ¹Brain Research Institute, University of Zurich, Zurich, Switzerland
• ²Department of Health, Sciences and Technology, ETH Zurich, Zurich, Switzerland

After stroke the central nervous system reveals a spectrum of intrinsic capacities to react as a highly dynamic system which can change the properties of its circuits, form new contacts, erase others, and remap related cortical and spinal cord regions. This plasticity can lead to a surprising degree of spontaneous recovery. It includes the activation of neuronal molecular mechanisms of growth and of extrinsic growth promoting factors and guidance signals in the tissue. Rehabilitative training and pharmacological interventions may modify and boost these neuronal processes, but almost nothing is known on the optimal timing of the different processes and therapeutic interventions and on their detailed interactions. Finding optimal rehabilitation paradigms requires an optimal orchestration of the internal processes of re-organization and the therapeutic interventions in accordance with defined plastic time windows. In this review we summarize the mechanisms of spontaneous plasticity after stroke and experimental interventions to enhance growth and plasticity, with an emphasis on anti-Nogo-A immunotherapy. We highlight critical time windows of growth and of rehabilitative training and consider different approaches of combinatorial rehabilitative schedules. Finally, we discuss potential future strategies for designing repair and rehabilitation paradigms by introducing a “3 step model”: determination of the metabolic and plastic status of the brain, pharmacological enhancement of its plastic mechanisms, and stabilization of newly formed functional connections by rehabilitative training.

Introduction

The human brain works wonders to fulfill the requirements of every-day life. These unique capacities are then fully esteemed when all of a sudden even simple activities fail or become a problem: cerebral strokes leave the victims with often large psychical and physical impairments—from vision problems to aphasia and motor deficits—leading to the number one cause of adult disability worldwide with great impact on public health. In the acute phase, “time is brain”—ruptured blood vessels (hemorrhagic stroke) or aggregates of platelets and blood cells that clog cerebral blood vessels (ischemic stroke) cause acute shortage of glucose and oxygen resulting in metabolic distress and long-term neuronal cell loss. The destruction process is complex and can only be dampened in the case of the ischemic stroke by very early intervention (within 4–6 h) with thrombolysis, (Hacke et al., 2008). Currently, only about 10% of all stroke patients reach a hospital early enough or fulfill the criteria for being able to receive thrombolysis in the therapeutic time window. Prognosis and recovery then depend on the location and extent of the stroke lesion. Clinically, the most successful therapy to further enhance this recovery of function is rehabilitative training.(Notice that your doctor has no place in your recovery, they let your neurons die off in the first week) Rehabilitation as a term “to reach and maintain optimal functioning in physical, intellectual, psychological and/or social domains” (WHO. International classification of functioning disability Health ICF. Geneva: WHO; 2001) is evidence based medicine and does not exclude a specific subgroup of patients.

Nevertheless, for many rehabilitative interventions, in particular those for long-term or chronic rehabilitation, robust data or adequately controlled studies are lacking (Quinn et al., 2009): e.g., comparisons between different training methods in current use could not show that any particular physiotherapy or stroke rehabilitation strategy is superior to another (Johansson, 2000).

Consequently optimal rehabilitation strategies can only be defined if we understand the way in which training and the rehabilitation protocol influences the neurobiology of the central nervous system with priority on the aspects of timing, kind and intensity of rehabilitative training. Measurable endpoint criteria for rehabilitative outcome are required in order to achieve two purposes: the adjustment of the ideal rehabilitative strategy to the individual patient, and the choice of the optimal therapy protocol.

In this review we focus on mechanisms of spontaneous recovery after stroke, on rehabilitative designs to enhance plasticity, on growth promoting mechanisms with an emphasis on anti-Nogo-A immunotherapy, and on the time windows of rehabilitative training and pharmacological interventions and the combination of both.

Much more at link. Does your doctor know about any of this stuff?