Ischemic stroke is a vascular disease affecting neuronal function. The ‘bimodal response’ of the neurovascular unit (NVU) to brain ischemia is characterized by an early blood-brain-barrier (BBB) disruption followed later by vascular remodeling and, hence, a switch from brain injury to repair and recovery. Acute effects include endothelium-dependent vasodilation, cerebral blood flow ( CBF ) regulation and mechanisms of BBB breakdown. However, weeks after brain ischemia, the complex mechanisms underlying post-stroke angiogenesis and vessel maturation contribute to improved long-term stroke outcome. Current work within the neurovascular field investigates the impact of metabolites (e.g. trimethyllysine and propionate) and the hippo-signaling pathway on post-stroke angiogenesis and outcome.

Another main research interest is to investigate and modulate the brain’s inflammatory response to ischemic damage. The complexity and Janus-faced nature of post-stroke neuro-inflammation, which evolves with time and may have widely varying effects during the early versus subacute phases following focal brain ischemia, remains a huge challenge in stroke research. Specifically, we focus on the diverse roles of resident versus invading CNS myeloid cells (i.e., resident microglia versus the monocyte-derived macrophages recruited from the circulation) in shaping stroke outcome.

When considered from a mental-health perspective, stroke can be conceptualized as a disruptive and highly traumatic event that may precipitate a host of psychological problems, including posttraumatic stress disorder (PTSD) and depressive symptoms. However, there is growing evidence of a bidirectional relationship between neuropsychiatric disorders and stroke. The pathomechanisms underlying the development of post-stroke depression (PSD) and PTSD remain poorly understood. Our current research focus lays on genetic models (e.g., Tph2 knockout mice lacking brain serotonin mice) and pharmacological interventions (SSRI, SSRE) to elucidate the effects of serotonergic signaling on stroke outcome. In addition, we study systemic effects of stress on metabolic and cardiac function. Furthermore, we recently finished the translational SATURN study in stroke survivors (ClinicalTrials.gov Identifier: NCT03496480). We found that a history of trauma exposure in tandem with endorsing subsequent PTSD symptoms was linked with significantly increased post-stroke PTSD and depressive symptoms together with decreased psychological well-being.