Encouraging an excitable brain state: mechanisms of brain repair in stroke

Stroke induces a plastic state in the brain. This period of enhanced plasticity leads to the sprouting of new axons, the formation of new synapses and the remapping of sensory-motor functions, and is associated with motor recovery. This is a remarkable process in the adult brain, which is normally constrained in its levels of neuronal plasticity and connectional change. Recent evidence indicates that these changes are driven by molecular systems that underlie learning and memory, such as changes in cellular excitability during memory formation. This Review examines circuit changes after stroke, the shared mechanisms between memory formation and brain repair, the changes in neuronal excitability that underlie stroke recovery, and the molecular and pharmacological interventions that follow from these findings to promote motor recovery in animal models. From these findings, a framework emerges for understanding recovery after stroke, central to which is the concept of neuronal allocation to damaged circuits. The translation of the concepts discussed here to recovery in humans is underway in clinical trials for stroke recovery drugs. Stroke initially causes cell injury and death. After these acute events, there is a period of increased plasticity in the brain. Joy and Carmichael review changes in neuronal excitability systems during this period that lead to neural circuit reformation after stroke and how they may be targeted to promote functional recovery.