In acute neurodegenerative disorders, following a sudden insult, neurons are rapidly damaged and usually die but cellular loss can occur hours and days thereafter. These diseases cause massive morbidity and mortality and tremendous economic and societal burden, especially ischemic stroke, which is a leading cause of death and disability with no effective treatment to promote recovery. The brain responds to a stroke, i.e., occlusion of a cerebral artery, with an inflammatory process characterized by rapid activation of resident cells including microglia and astrocytes, production of proinflammatory mediators, and infiltration of various types of immune cells. Recent studies have suggested that the local inflammation is not only detrimental but can also be beneficial for the repair process. Our proposal unites 7 leading academic teams and 2 experienced SMEs and aims to develop a pre-clinical protocol for immunomodulation leading to enhancement of cellular plasticity and improved functional recovery in stroke patients. To achieve this goal we will study the temporal and spatial role of inflammatory cells in stroke-induced brain damage and determine the action of inflammatory cells in the activation and support of regenerative processes, including the formation of new neurons from endogenous and transplanted neural stem cells (NSCs). We will investigate the ability of transplanted NSCs to modulate the inflammatory response and to affect the characteristics of the stroke-induced lesion and subsequent recovery. The overriding social objective of our project is to develop a novel therapeutic strategy which will shorten the recovery phase, minimize the motor impairments, and improve the patients’quality of life after stroke.