Repairing the human brain after stroke. II. Restorative therapies

Spontaneous behavioral recovery is usually limited after stroke, making stroke a leading source of disability. A number of therapies in development aim to improve patient outcomes not by acutely salvaging threatened tissue, but instead by promoting repair and restoration of function in the subacute or chronic phase after stroke. Examples include small molecules, growth factors, cell-based therapies, electromagnetic stimulation, device-based strategies, and task-oriented and repetitive training-based interventions. Stage of development across therapies varies widely, from preclinical to late-phase clinical trials. The optimal methods to prescribe such therapies require further studies, for example, to best identify appropriate patients or to guide features of dosing. Likely, anatomic, functional, and behavioral measures of brain state, as well as measures of injury, will each be useful in this regard. Considerations for clinical trials of restorative therapies are provided, emphasizing both similarities and points of divergence with acute stroke clinical trial design.