Background: Stroke induces long-lasting and profound neuroinflammation, revealing a deficit in efficient resolution of inflammation.
Hypothesis: We hypothesize that microglia are a critical checkpoint in the resolution of inflammation and recovery of functional deficits after stroke.
Strategy: This project will investigate the switch from an activated to homeostatic microglial function and the pathophysiological mechanisms which impede this checkpoint in order to improve recovery in an experimental stroke model.


Stroke induces a plethora of immune responses well comparable to those occurring in primary inflammatory brain disorders, such as multiple sclerosis. We have recently identified that acute brain ischemia not only induces acute inflammation but results in long-lasting and profound neuroinflammation. These novel observations reveal a surprising deficit in resolving inflammation after acute brain injury in contrast to acute tissue injuries of other organs such as myocardial infarction. Normalization of microglial polarization to a homeostatic phenotype is the critical checkpoint in resolution of neuroinflammation after stroke. In preliminary experiments, we have identified by transcriptomic analysis a failure of homeostatic recovery of microglia in the chronic phase after stroke. These findings suggest either a deficiency in endogenous resolution mechanisms such as the anti-inflammatory properties of regulatory T cells or a preponderance of currently unknown mechanisms driving chronic immune activation. Chronic microglial activation can result in secondary neuronal cell death or dysfunction and impair neuronal plasticity which is necessary for post-stroke recovery. Therefore, this project will investigate mechanisms impeding the return to homeostatic microglial function and explore novel therapeutic strategies to modulate this critical checkpoint in the resolution of post-stroke chronic neuroinflammation.

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Principal investigator

Arthur Liesz

Prof. Dr. Arthur Liesz

Institute for Stroke and Dementia Research
Feodor-Lynen-Str. 17, 81377 Munich
Tel: + 49-(0)89-4400-46169