Functional Recovery after Experimental Stroke in Mice- Involvement of Enriched Environment, BDNF and Cell Genesis

Sammanfattning: Stroke is caused by an obstruction of blood flow to a part of the brain, resulting in brain damage. Stroke is the third most common cause of death in the industrialized world, and the primary cause of adult-onset disability. There is a spontaneous recovery of function after stroke but several factors, such as the environment can influence the speed and extent of this recovery. This thesis deals with functional recovery after an experimental stroke in mice and how the surrounding environment can influence on such recovery. Housing mice in an enriched environment, with both physical and social stimulation, results in an improved motor function after focal ischemia. However stimulation must maintain for at least a month for stable recovery. The enriched environment affects gene expression as well as cell genesis in the brain. We show that a low endogenous level of BDNF leads to an improved motor function after stroke, similar to the improvement caused by exposure to the enriched environment. It has previously been shown that housing post-ischemic animals in a stimulating environment leads to a downregulation of the neurotrophic factor BDNF, indicating that a low level of BDNF is beneficial for motor function after stroke. In general this thesis shows that the effect of enriched environment on motor function after an experimental stroke is different to the affected pathways stimulated by the environment in the intact brain. Both the gene expression of NGFI-A and vimentin is downregulated after exposure to an enriched environment after stroke, as well as a downregulation of the level of cell genesis and cell migration to the striatum. The thesis suggests that the enriched environment appears to provide relevant sensori-motor input to the neuronal networks during the recovery phase, structuring gene expression and depressing redundant cell genesis, leading to an improved motor function in mice.