Four Birds with One Stone Reparative, neuroplastic, cardiorespiratory and metabolic benefits of aerobic exercise post-stroke

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Cameron Baker
5 years ago
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, PhD Canada Research Chair (Tier II); Rehabilitation, Neuroplasticity and Brain Recovery

1 Four Birds with One Stone Reparative, neuroplastic, cardiorespiratory and metabolic benefits of aerobic exercise post-stroke Michelle Ploughman BSc.PT, MSc., PhD Canada Research Chair (Tier II); Rehabilitation, Neuroplasticity and Brain Recovery Assistant Professor, Physical Medicine & Rehabilitation Faculty of Medicine, Memorial University of Newfoundland, St. John s NL Canada

2 Objectives Stroke recovery and the limited window of neuroplasticity The mismatch between research and practice Aerobic exercise effects on brain repair Aerobic exercise effects on neuroplasticity and neurological recovery Cardiorespiratory and metabolic benefits of aerobic exercise in subacute stroke Results of recent trials

3 Percentage of maximum recovery achieved

4 N=94

5 Neurobiological window in animal models Murphy and Corbett Nature Reviews Neuroscience 2009

6 A neurorehabilitation ceiling? Stroke patients have extremely low activity tolerance Such low fitness levels create a ceiling to neuromotor recovery ; limiting both the number of repetitions that can be completed within a session and the total intensity at which they can be sustained. For example, routine rehabilitation reaches about 4.5 METS, levels not achievable by most stroke patients.

7 Factors conspire against optimal recovery Extremely low activity tolerance (fitness levels) creates a ceiling for neuromotor practice Humans are optimizers so will quickly learn to move in any way possible; early compensatory strategies Heightened safety culture Early fitting of AFO s and canes to hasten discharge No one seems to have ownership of the patient s overall after hours activity levels Other concomitant physical, cognitive and mood issues

8 Could care on a stroke rehabilitation unit be considered stroke recovery boot camp?

11 6855 stroke patients in 14 acute hospitals J Stroke Cerebrovasc Dis May 2018 Rehabilitation database included amount of therapy, types of activities, prescription of orthotics, counselling, education, recreational programming, weekend services etc.

12 Median FIM efficiency 1.0

14 Objectives Stroke recovery and the limited window of neuroplasticity The mismatch between research and practice Aerobic exercise effects on brain repair Aerobic exercise effects on neuroplasticity and neurological recovery Cardiorespiratory and metabolic benefits of aerobic exercise in subacute stroke Results of recent trial

15 METABOLIC HEALTH BRAIN REPAIR Lesion size, cell death, inflammation NEUROLOGICAL OUTCOMES Relearning of skilled movements, executive function CARDIORESPIRATORY FITNESS PLASTICITY Neurotrophins, neuroplasticity markers, fmri, TMS

16 Lesion Volume Inflammation/ cell death Neurogenesis Angiogenesis Stress

17 20-30 min early-initiated (1-3 days post-ischemia), low intensity walking exercise instituted most days of the week reduced both lesion volume (33 studies) and markers of cell death ( 11 studies). Longer interventions (2-4 weeks) resulted in greater tissue rescue. Lower intensity exercise reduced lesion volume more than higher intensities

18 Aerobic exercise effects on neuroplasticity and neurological recovery

19 Understanding how the brain recovers after stroke Work of R. Nudo

Percent Change in Spared Representations Area One Month After Infarct 40 20 0-20 -40-60 -80 Distal Forelimb Spontaneous Recovery

21 Percent Change in Spared Representations Area One Month After Infarct Distal Forelimb Spontaneous Recovery Jacket/No Training Jacket/Rehabilitative Training Digit Wrist/Forearm Adapted from Nudo RJ, Science 1996, J Neurophysiol 1996, J Neurosci 1996

22 Murphy and Corbett Nature Reviews Neuroscience 2009

23 How much exercise in enough?? BDNF levels in the intact cortex

25 Functional improvement was paralleled by enhanced dendritic branching within the motor cortex (Ploughman et al 2007 European Journal of Neuroscience)

26 EXERCISE & ENRICHED ENVIRONMENT INCREASES MIGRATION AND SURVIVAL OF STEM CELLS Hicks et al, Neuroscience 2007

27 IS BDNF THE BIG PLAYER?

28 Evidence for a critical window

29 Rules of Neuroplasticity Time-dependency: Upregulation of growth proteins after stroke create an optimal environment for neuroplasticity Neuroplasticity and recovery are reduced when rehabilitation is delayed Neuroplasticity and recovery occurs best during a critical window Dose-dependency: Neuroplasticity and recovery require highly intense task-specific training (1000s of repetitions)

30 BDNF: moderate (but not high) intensity, 30min/day for 14 or more days, 3-7 days post-stroke (but not immediate training). IGF-1 increased with daily high-intensity. Synaptic proteins: moderate to high intensity 14 or more days.

32 METABOLIC HEALTH BRAIN REPAIR Lesion size, cell death, inflammation NEUROLOGICAL OUTCOMES Relearning of skilled movements, executive function CARDIORESPIRATORY RY FITNESS PLASTICITY Neurotrophins, neuroplasticity markers, fmri, TMS

33 BRAIN REPAIR Lesion size, cell death, inflammation METABOLIC HEALTH NEUROLOGICAL OUTCOMES Relearning of skilled movements, executive function CARDIORESPIRATORY FITNESS PLASTICITY Neurotrophins, neuroplasticity markers, fmri, TMS

Cardiorespiratory and metabolic benefits of aerobic exercise in subacute stroke Studies examining the

moderate to severe impairment (Teixeira da Cunha 2001, McKay-Lyons 2013, Tang 2009, Sandberg 2016, Wang

) Optimal training 3-5 days/week, moderate to vigourous intensity (lower intensity, less benefit),

34 Cardiorespiratory and metabolic benefits of aerobic exercise in subacute stroke Studies examining the effects of AE show that AE can be safely implemented as early as 5 days after stroke even among those with moderate to severe impairment (Teixeira da Cunha 2001, McKay-Lyons 2013, Tang 2009, Sandberg 2016, Wang 2014,.) Optimal training 3-5 days/week, moderate to vigourous intensity (lower intensity, less benefit), 20-60min/session, 3-12 weeks. Using cardiac rehabilitation model in people with mild stroke who are community-living reduced cardiovascular risk scores, reduces fasting insulin and glucose tolerance. Lipid profile not altered.

35 Optimal training parameters to cut across all domains Frequency 3-5 X week Intensity >60% maximum (Vigorous) 30 min >8 weeks Continuous (emerging evidence for HIIT)

37 Objectives Stroke recovery and the limited window of neuroplasticity The mismatch between research and practice Aerobic exercise effects on brain repair Aerobic exercise effects on neuroplasticity and neurological recovery Cardiorespiratory and metabolic benefits of aerobic exercise in subacute stroke Results of recent trial

38 Two-site RCT Primary Outcome Raven s Progressive Matrices Test

39 DUAL-n-BACK (COG) AEROBIC ACTIVITY GAMES

41 Fitness Walking speed

42 Responsiveness of IGF-1 at baseline predicted 40% variability in cognitive outcome

46 This project was supported by grants from the Heart and Stroke Foundation Canadian Partnership for Stroke Recovery (MP, JM), the Canada Research Chairs program (MP), the Canada Foundation for Innovation (MP), The Newfoundland & Labrador Research and Development Corporation (MP), the Nova Scotia Health Research Foundation (MML), Capital Health Research Foundation, Halifax Nova Scotia (MML) and the Dalhousie University Faculty of Health Professions Innovation Fund (MML).

47 BRAIN REPAIR Lesion size, cell death, inflammation METABOLIC HEALTH NEUROLOGICAL OUTCOMES Relearning of skilled movements, executive function CARDIORESPIRATORY FITNESS PLASTICITY Neurotrophins, neuroplasticity markers, fmri, TMS

48 Arthur Chaves PhD student Liz Wallack Marie Curtis Dr. Katie Wadden post-doc Megan Kirkland MD-PhD student Augustine Devasahayam PhD student Liam Kelly PhD student

8:30 9:30 9:30 10:15. Learning Objectives 1. Understand the different mechanisms through which hearing loss could affect

8:30 9:30 9:30 10:15. Learning Objectives 1. Understand the different mechanisms through which hearing loss could affect TIME PROGRAM TITLE 7:30 8:20 Registration and Continental Breakfast 8:20 8:30 Opening Remarks Four Birds with One Stone: Reparative, Neuroplastic, Cardiorespiratory and Metabolic Benefits of Aerobic Exercise