Review ArticleMolecular, cellular and functional events in axonal sprouting after stroke

•Stroke induces the formation of new connections in brain and spinal cord.•These mediate some aspects of motor recovery.•A unique molecular program, a regenerative transcriptome, underlies post-stroke axonal sprouting.•Axonal sprouting occurs in three different patterns: reactive, reparative and unbounded.•Each pattern of post-stroke axonal sprouting has unique relationships to behavioral activity and molecular control points.

Stroke is the leading cause of adult disability. Yet there is a limited degree of recovery in this disease. One of the mechanisms of recovery is the formation of new connections in the brain and spinal cord after stroke: post-stroke axonal sprouting. Studies indicate that post-stroke axonal sprouting occurs in mice, rats, primates and humans. Inducing post-stroke axonal sprouting in specific connections enhances recovery; blocking axonal sprouting impairs recovery. Behavioral activity patterns after stroke modify the axonal sprouting response. A unique regenerative molecular program mediates this aspect of tissue repair in the CNS. The types of connections that are formed after stroke indicate three patterns of axonal sprouting after stroke: reactive, reparative and unbounded axonal sprouting. These differ in mechanism, location, relationship to behavioral recovery and, importantly, in their prospect for therapeutic manipulation to enhance tissue repair.