Stroke recovery activity-dependent mechanisms

Abstract: Stroke is the leading cause of disability in developed countries and among the major causes of death worldwide. During a stroke, neurons deprived of their normal metabolic substrates cease to function in seconds and show signs of structural damage after only a few minutes which result in the impairment of sensory and motor function. Loss of function after stroke is due to neuronal death and irreversible ischemic damage in the infarct core but also to cell dysfunction in the areas surrounding the infarct. These areas represent the peri-infarct, a region of reduced blood supply and reversible damage, and the intact remote areas directly connected to the damaged tissue or hub regions of the brain network.Clinical evidence shows that physical and cognitive therapy, as well as social interactions, facilitate the recovery process and promote improvement of lost neurological function after stroke. In the experimental setting, these observations can be mimicked by an enriched environment (EE), which provides an activity-dependent stimulation of the brain. The EE is a housing condition for rodents combining multisensory stimulation and social interactions that improve lost neurological function without affecting the extent of brain damage after experimental stroke.This thesis deals with the concept of EE and mechanisms underlying activity-dependent plasticity in the brain after stroke and their influence on functional recovery. We propose that EE balances mechanisms critical for stroke recovery, such as the detrimental and beneficial components of the post-stroke inflammatory response, and the activation of ECM-degrading processes which ultimately lead to improved brain functional connectivity and behavioral outcome. Finally, this thesis suggests that a general stimulating and positive environment can be the optimal base for specific interventions in neurological rehabilitation.