Translating the frontiers of brain repair to treatments: starting not to break the rules.

The field of neural repair in stroke has identified cellular systems of reorganization and possible molecular mechanisms. Conceptual barriers now limit the generation of clinically useful agents. First, it is not clear what the causal mechanisms of neural repair are in stroke. Second, adequate delivery systems for neural repair drugs need to be determined for candidate molecules. Third, ad hoc applications of existing pharmacological agents that enhance attention, mood or arousal to stroke have failed. New approaches that specifically harness the molecular systems of learning and memory provide a new avenue for stroke repair drugs. Fourth, combinatorial treatments for neural repair need to be considered for clinical therapies. Finally, neural repair therapies have as a goal altering brain connections, cognitive maps and active neural networks. These actions may trigger a unique set of "neural repair side effects" that need to be considered in planning clinical trials.