Figure 1.

Overview of inflammatory pathways and imaging targets in the CNS and periphery. (A) Interplay between gut and the brain as an important route for inflammatory signals from and to the brain influencing stroke outcome. (B) Overview of key infiltration routes of peripheral innate and adaptive immune cells. Peripheral immune cells can enter into the ischemic brain from the (i) subarachnoid space (SAS), (ii) direct crossing of the blood brain barrier, and (iii) the choroid plexus across the blood-cerebrospinal fluid (CSF) barrier. (C) Dysregulated microbiota and resident intestinal immune cells send inflammatory mediators including cytokines via the hypothalamus-pituitary-adrenal glands axis (HPA), the autonomic nervous system, and the enteric nervous system (ENS). (D) Detailed view of the inflammatory events after ischemic stroke at the neurovascular unit (NVU) and SAS. CNS-resident microglia and astrocytes become activated and, depending on their polarization state, promote disease progression and repair. Resident and infiltrating immune cells exert their bi-modal functions via cell contact-dependent mechanisms and through the action of soluble inflammatory mediators. The NVU represents the target structure for functional tissue repair by neuroinflammatory processes. The NVU components may serve as imaging targets for the investigation of novel image-guided therapies targeting the rescue of NVU function.