Getting neurorehabilitation right: what can be learned from animal models?
TL;DR: Translation from animal models will require substantial increases in the intensity and dosage of treatments offered in the first month after stroke with an emphasis on impairment and combinational approaches such as noninvasive brain stimulation with robotics, based on current understanding of motor learning and brain plasticity.
Abstract: Animal models suggest that a month of heightened plasticity occurs in the brain after stroke, accompanied by most of the recovery from impairment. This period of peri-infarct and remote plasticity is associated with changes in excitatory/inhibitory balance and the spatial extent and activation of cortical maps and structural remodeling. The best time for experience and training to improve outcome is unclear. In animal models, very early ( 30 days) is much less effective both in terms of outcome and morphological changes associated with plasticity. In clinical practice, rehabilitation after disabling stroke involves a relatively brief period of inpatient therapy that does not come close to matching intensity levels investigated in animal models and includes the training of compensatory strategies that have minimal impact on impairment. Current rehabilitation treatments have a disappointingly modest effect on impairment early or late after stroke. Translation from animal models will require the following: (1) substantial increases in the intensity and dosage of treatments offered in the first month after stroke with an emphasis on impairment; (2) combinational approaches such as noninvasive brain stimulation with robotics, based on current understanding of motor learning and brain plasticity; and (3) research that emphasizes mechanistic phase II studies over premature phase III clinical trials.
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TL;DR: Understanding the multifaceted roles of astrocytes in the healthy and diseased CNS will undoubtedly contribute to the development of treatment strategies that will, in a context-dependent manner and at appropriate time points, modulate reactive astrogliosis to promote brain repair and reduce the neurological impairment.
Abstract: Astrocytes are the most abundant cells in the central nervous system (CNS) that provide nutrients, recycle neurotransmitters, as well as fulfill a wide range of other homeostasis maintaining functions During the past two decades, astrocytes emerged also as increasingly important regulators of neuronal functions including the generation of new nerve cells and structural as well as functional synapse remodeling Reactive gliosis or reactive astrogliosis is a term coined for the morphological and functional changes seen in astroglial cells/astrocytes responding to CNS injury and other neurological diseases Whereas this defensive reaction of astrocytes is conceivably aimed at handling the acute stress, limiting tissue damage, and restoring homeostasis, it may also inhibit adaptive neural plasticity mechanisms underlying recovery of function Understanding the multifaceted roles of astrocytes in the healthy and diseased CNS will undoubtedly contribute to the development of treatment strategies that will, in a context-dependent manner and at appropriate time points, modulate reactive astrogliosis to promote brain repair and reduce the neurological impairment
668 citations
Florey Institute of Neuroscience and Mental Health1, University of British Columbia2, Northwestern University3, VU University Amsterdam4, UCL Institute of Neurology5, Emory University6, Johns Hopkins University7, University of California, Los Angeles8, Heart and Stroke Foundation of Canada9, University of Ottawa10, University of California, Irvine11
TL;DR: This paper outlines the working definitions established by the Stroke Recovery and Rehabilitation Roundtable group and an agreed vision for accelerating progress in stroke recovery research.
Abstract: 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.
608 citations
TL;DR: The higher dose, very early mobilisation protocol was associated with a reduction in the odds of a favourable outcome at 3 months and should affect clinical practice by refining present guidelines; however, clinical recommendations should be informed by future analyses of dose-response associations.
568 citations
TL;DR: The two models mimicking human stroke most closely are various embolic stroke models and spontaneous stroke models, which more closely mimics the therapeutic situation of mechanical thrombectomy which is expected to be increasingly applied to stroke patients.
Abstract: The vast majority of cerebral stroke cases are caused by transient or permanent occlusion of a cerebral blood vessel (“ischemic stroke”) eventually leading to brain infarction. The final infarct size and the neurological outcome depend on a multitude of factors such as the duration and severity of ischemia, the existence of collateral systems and an adequate systemic blood pressure, etiology and localization of the infarct, but also on age, sex, comorbidities with the respective multimedication and genetic background. Thus, ischemic stroke is a highly complex and heterogeneous disorder. It is immediately obvious that experimental models of stroke can cover only individual specific aspects of this multifaceted disease. A basic understanding of the principal molecular pathways induced by ischemia-like conditions comes already from in vitro studies. One of the most frequently used in vivo models in stroke research is the endovascular suture or filament model in rodents with occlusion of the middle cerebral artery (MCA), which causes reproducible infarcts in the MCA territory. It does not require craniectomy and allows reperfusion by withdrawal of the occluding filament. Although promptly restored blood flow is far from the pathophysiology of spontaneous human stroke, it more closely mimics the therapeutic situation of mechanical thrombectomy which is expected to be increasingly applied to stroke patients. Direct transient or permanent occlusion of cerebral arteries represents an alternative approach but requires craniectomy. Application of endothelin-1, a potent vasoconstrictor, allows induction of transient focal ischemia in nearly any brain region and is frequently used to model lacunar stroke. Circumscribed and highly reproducible cortical lesions are characteristic of photothrombotic stroke where infarcts are induced by photoactivation of a systemically given dye through the intact skull. The major shortcoming of this model is near complete lack of a penumbra. The two models mimicking human stroke most closely are various embolic stroke models and spontaneous stroke models. Closeness to reality has its price and goes along with higher variability of infarct size and location as well as unpredictable stroke onset in spontaneous models versus unpredictable reperfusion in embolic clot models.
381 citations
TL;DR: Several large intervention trials targeting motor recovery report that participants' motor performance improved, but to a similar extent for both the intervention and control groups in most trials.
Abstract: Stroke remains a leading cause of adult disability and the demand for stroke rehabilitation services is growing. Substantial advances are yet to be made in stroke rehabilitation practice to meet this demand and improve patient outcomes relative to current care. Several large intervention trials targeting motor recovery report that participants' motor performance improved, but to a similar extent for both the intervention and control groups in most trials. These neutral results might reflect an absence of additional benefit from the tested interventions or the many challenges of designing and doing large stroke rehabilitation trials. Strategies for improving trial quality include new approaches to the selection of patients, control interventions, and endpoint measures. Although stroke rehabilitation research strives for better trials, interventions, and outcomes, rehabilitation practices continue to help patients regain independence after stroke.
338 citations
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TL;DR: The four articles in this special section onMeta-analysis illustrate some of the complexities entailed in meta-analysis methods and contributes both to advancing this methodology and to the increasing complexities that can befuddle researchers.
Abstract: During the past 30 years, meta-analysis has been an indispensable tool for revealing the hidden meaning of our research literatures. The four articles in this special section on meta-analysis illus...
20,272 citations
TL;DR: This chapter describes the most important sources and the types of data the AHA uses from them and other government agencies to derive the annual statistics in this Update.
Abstract: 1. About These Statistics…e70
2. Cardiovascular Diseases…e72
3. Coronary Heart Disease, Acute Coronary Syndrome, and Angina Pectoris…e89
4. Stroke…e99
5. High Blood Pressure…e111
6. Congenital Cardiovascular Defects…e116
7. Heart Failure…e119
8. Other Cardiovascular Diseases…e122
9. Risk Factor: Smoking/Tobacco Use…e128
10. Risk Factor: High Blood Cholesterol and Other Lipids…e132
11. Risk Factor: Physical Inactivity…e136
12. Risk Factor: Overweight and Obesity…e139
13. Risk Factor: Diabetes Mellitus…e143
14. End-Stage Renal Disease and Chronic Kidney Disease…e149
15. Metabolic Syndrome…e151
16. Nutrition…e153
17. Quality of Care…e155
18. Medical Procedures…e159
19. Economic Cost of Cardiovascular Diseases…e162
20. At-a-Glance Summary Tables…e164
21. Glossary and Abbreviation Guide…e168
Writing Group Disclosures…e171
Appendix I: List of Statistical Fact Sheets:
http://www.americanheart.org/presenter.jhtml?identifier=2007
We thank Drs Robert Adams, Philip Gorelick, Matt Wilson, and Philip Wolf (members of the Statistics Committee or Stroke Statistics Subcommittee); Brian Eigel; Gregg Fonarow; Kathy Jenkins; Gail Pearson; and Michael Wolz for their valuable comments and contributions. We would like to acknowledge Tim Anderson and Tom Schneider for their editorial contributions and Karen Modesitt for her administrative assistance.
# 1. About These Statistics {#article-title-2}
The American Heart Association (AHA) works with the Centers for Disease Control and Prevention’s National Center for Health Statistics (CDC/NCHS); the National Heart, Lung, and Blood Institute (NHLBI); the National Institute of Neurological Disorders and Stroke (NINDS); and other government agencies to derive the annual statistics in this Update. This chapter describes the most important sources and the types of data we use from them. For more details and an alphabetical list of abbreviations, see Chapter 21 of this document, the Glossary and Abbreviation Guide.
The surveys used are:
5,393 citations
"Getting neurorehabilitation right: ..." refers background in this paper
...Stroke is the leading cause of disability among adults, and hemiparesis is the most common impairment after stroke.(1) Animal models suggest a time-limited window of heightened plasticity in the brain early after stroke when most recovery from impairment occurs....
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TL;DR: The statistical update brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update.
Abstract: We thank Drs Sean Coady, Eric L. Ding, Brian Eigel, Gregg C. Fonarow, Linda Geiss, Cherie James, Michael Mussolino, and Michael Wolz for their valuable comments and contributions. We acknowledge Tim Anderson and Tom Schneider for their editorial contributions, and Karen Modesitt for her administrative assistance.
Disclosures
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# Summary {#article-title-2}
Each year, the American Heart Association, in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay …
5,019 citations
TL;DR: Each year the American Heart Association brings together the most up-to-date statistics on heart disease, stroke, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update.
Abstract: We thank Drs Robert Adams, Gary Friday, Philip Gorelick, and Sylvia Wasserthiel-Smoller, members of Stroke Statistics Subcommittee; Drs Joe Broderick, Brian Eigel, Kimberlee Gauveau, Jane Khoury, Jerry Potts, Jane Newburger, and Kathryn Taubert; and Sean Coady and Michael Wolz for their valuable comments and contributions. We acknowledge Tim Anderson and Tom Schneider for their editorial contributions and Karen Modesitt for her administrative assistance.
View this table:
Writing Group Disclosures
# Summary {#article-title-2}
Each year the American Heart Association, in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media, the lay public, and many others who seek the …
4,962 citations
TL;DR: 10 principles of experience-dependent neural plasticity and considerations in applying them to the damaged brain are reviewed from the perspective of basic neuroscientists but in a manner intended to be useful for the development of more effective clinical rehabilitation interventions.
Abstract: Purpose This paper reviews 10 principles of experience-dependent neural plasticity and considerations in applying them to the damaged brain. Method Neuroscience research using a variety of models o...
1,907 citations