Stroke and Functional Recovery - An experimental study on environmental influence and gene expression after cortical infarcts in the rat

Sammanfattning: Abstract Stroke is the third leading cause of death in the western world, and the number one cause of disability. 85% of all strokes are ischemic. Most stroke survivors will experience recovery of function. The mechanisms behind this improvement are partly unknown, but may involve elements of both compensation and restoration. Exposure to an enriched environment (EE) that stimulates social interaction, expanded learning abilities and spontaneous physical activity which also consists elements of training, alters behaviour and brain morphology with an increase in dendritic branching and number of synapses in intact animals. Enriched housing after a cortical infarct improves functional outcome. This thesis is based on studies of cortical infarcts in rats and demonstrates that management and housing conditions after an experimental stroke significantly alters functional outcome. To examine the influence of different environmental conditions on functional recovery and potential mediators of brain plasticity, we compared rats housed in an enriched or social environment with rats housed in isolation with or without access to a running wheel. EE or social interaction resulted in significantly higher mRNA expression of NGFI-A and NGFI-B in regions outside the infarct and this was correlated to better outcome compared to running or isolated housing. The observed differences in functional recovery were not related to changes in gene expression of BDNF. Housing animals in an EE with the opportunity to engage in various activities without specific training significantly improves functional outcome and does not increase tissue loss. However additional training initiated 24 h after MCAo resulted in an increase in infarct volume without affecting functional outcome as early trained rats housed in EE improved more than standard rats in the behavioural tests used. Stroke induces a stress reaction with an increase in glucocorticoid (GC) levels, suggested to exaggerate neuronal damage and negatively affect outcome. We found that inhibition of GCs increases tissue loss, and failed to improve outcome, a result that partly might be due to dampening of the anti-inflammatory response provided by corticosterone. In conclusion the present thesis shows that postischemic EE can influence recovery and NGFI-A gene expression that may be related to better outcome. Enriched housing supporting voluntary activities improves outcome and does not increase tissue loss after a cortical infarct. However additional training initiated 24 h after MCA occlusion can increase infarct volume without negative effects on outcome. The stress response seen after stroke may have a beneficial effect as inhibition of GSs increases tissue loss and negatively affects outcome.