Mechanisms and challenges in translational stroke research

Abstract

Translating basic science advances into clinical meaning has been challenging for stroke research. This does not, however, mean that the investigation of basic mechanisms is irrelevant. Translation is difficult because the underlying mechanisms are complex and ill-defined. The original focus on neuroprotection has now evolved into a broader consideration of the role of non-neuronal cells in stroke pathophysiology. The neurovascular unit may provide a conceptual framework within which interactions between neural, glial, and vascular cells comprise a basis for function and dysfunction in the central nervous system. Importantly, these cell–cell signaling pathways are also biphasic in nature, that is, mechanisms that are deleterious in the acute phase may surprisingly be required for neurovascular remodeling and plasticity during stroke recovery. Furthermore, injury-into-repair gradients are significantly influenced by a host of modifying factors and comorbidities. Rigorous dissection of these complex and recursive mechanisms should be required before they can be rationally targeted for stroke.