Cellular and molecular mechanisms of neural repair after stroke: making waves.

Stroke is associated with a limited degree of functional recovery. Imaging studies in humans have shown that reorganization in periinfarct and connected cortical areas most closely correlates with functional recovery after stroke. On a cellular level, two major regenerative events occur in periinfarct cortex: axons sprout new connections and establish novel projection patterns, and newly born immature neurons migrate into periinfarct cortex. Stroke induces a unique microenvironment for axonal sprouting in periinfarct cortex, in which growth-inhibitory molecules are reduced for 1 month after the infarct. During this period, neurons activate growth-promoting genes in successive waves. Neurogenesis also occurs through waves of migration of immature neurons from their origin in the subventricular zone into periinfarct cortex. This migration is mediated, in part, by the cytokine erythropoietin. These data indicate that the cellular environment after stroke is far from one of just death and destruction, but rather involves a longer evolving process of neuronal regeneration. Poststroke neuronal regeneration is characterized by waves of specific cellular and molecular events. Manipulating these waves of regeneration may provide for novel therapies that will improve recovery after stroke.