Promoting recovery from ischemic stroke

ABSTRACT

Over recent decades, experimental and clinical stroke studies have identified a number of neurorestorative treatments that stimulate neural plasticity and promote functional recovery. In contrast to the acute stroke treatments thrombolysis and endovascular thrombectomy, neurorestorative treatments are still effective when initiated days after stroke onset, which makes them applicable to virtually all stroke patients. In this article, selected physical, pharmacological and cell-based neurorestorative therapies are discussed, with special emphasis on interventions that have already been transferred from the laboratory to the clinical setting. We explain molecular and structural processes that promote neural plasticity, discuss potential limitations of neurorestorative treatments, and offer a speculative viewpoint on how neurorestorative treatments will evolve.

KEYWORDS:

• Ischemic stroke
• recovery
• regeneration
• neural plasticity
• neurorestorative treatments

Financial & competing interests disclosure

A Schmidt received a research grant of the Medical Faculty of the University of Münster. J Minnerup is supported by the Else Kröner-Fresenius-Stiftung (2014_EKES.16). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Stroke is the second most frequent cause of death and a major cause of adult disability and cognitive impairment in industrialized countries.

• Due to a narrow time window and strict eligibility criteria, the acute stroke treatments thrombolysis and endovascular thrombectomy are available for a minority of stroke patients.

• In the last decades, experimental and clinical studies have identified neurorestorative treatments that improve the functional recovery by promoting endogenous repair mechanisms like neurogenesis, angiogenesis and axonal remodeling.

• Neurorestorative treatments include physical treatments, pharmacological treatments, the application of growth factors and cell therapies.

• In contrast to acute stroke treatments, neurorestorative treatments are still effective, when initiated days after stroke onset.

• In contrast to neuroprotective approaches, recovery-enhancing treatments have already demonstrated successful translation from animal stroke studies to large clinical trials.

• Factors like age and comorbidities, which have an impact on endogenous repair mechanisms, may compromise the treatment effect, but neurorestorative therapies have still demonstrated efficacy in aged and diseased subjects.

• Constraint-induced movement therapy, physical fitness training and pharmacological treatments with selective serotonin reuptake inhibitors like fluoxetine have been successfully transferred from animal studies to the clinical setting.

• Among experimental treatments that have not been investigated in a clinical trial yet, Nogo-A inhibition is a particularly promising approach to enhance neuronal plasticity, even when initiated 9 weeks after stroke onset.