2013 Thomas Willis Award Lecture: Causation and collaboration for stroke research.

The pathophysiology of stroke is complex. Adaptive and maladaptive signalling occurs between multiple cell types in the brain. There is crosstalk between central and systemic responses. And there are overlapping pathways during initial injury and subsequent repair. These numerous feed-forward and feed-back interactions have made it difficult to translate experimental discoveries into clinical applications. An emerging hypothesis in biomedical research now suggests that contrary to a traditional model, translation may not be efficiently obtained without a rigorous understanding of mechanisms. Hence, to optimize diagnostics and therapeutics for stroke patients, it is necessary to identify and define causal mechanisms. Mirroring the multi-compartment interactions in stroke pathophysiology, bench-to-bedside, and bedside-back-to-bench advances in stroke may be best achieved with inter-disciplinary collaborations between basic research, neuroimaging, and broadly based clinical science. Causation can then be two-fold, ie, dissecting mechanisms and targets, as well as developing future scientists who can blur the boundaries between basic, translational, and clinical research. In systems theory, a critical goal is to distinguish causation from correlation. In stroke research, causation may perhaps be found through a collaborative search for mechanisms.