TOPIC NEUROLOGICAL DISEASES
The CNS harbors a unique vascular system, which provides sufficient oxygen and glucose levels to meet the high metabolic rate of the brain and protects sensitive neurons from toxic substances. Hence, the CNS endothelium differs from non-CNS endothelia in the presence of intercellular tight junctions as well as brain-specific enzymes and transport protein. Moreover, CNS capillaries have a higher coverage of pericytes (PCs), which regulate the formation of the blood-brain barrier (BBB). These PCs and the surrounding astroglial foot processes, the Glia limitans interna, form an additional continuous layer that separates the blood vessels from the brain parenchyma.
Stroke
In adults, the CNS vasculature is extremely stable under physiological conditions. However, this system can be structurally and functionally disrupted under acute pathological conditions such as ischemic stroke and traumatic brain injuries. A variety of cellular and molecular responses in the brain take place after ischemic stroke, including BBB breakdown, excitotoxicity, reactive free radical generation, inflammation, and ischemia-reperfusion injury. The disintegration of the BBB can be attributed to several processes including the death of PCs as well as the activation of matrix metalloproteinases, the upregulation of inflammatory cytokines, and the disruption of tight junctions.
Projects
The neurovascular factor EGFL7 stimulates blood vessel formation in vitro and in vivo acts by acting as a ligand for integrin αvβ3. Expression levels of EGFL7 are increased during physiological angiogenesis in the proliferating, migrating or remodeling endothelium as well as by pathological stimuli, such as arterial injury or hypoxia. We reported the upregulation of EGFL7 in the penumbra of stroke after cerebral ischemia using a reversible middle cerebral artery occlusion (MCAO) model, where it may contribute to the activation of microglia. Further, EGFL7 beneficially regulated CNS inflammation by affecting immune cell evasion in a model of multiples sclerosis. Currently, we further study these phenotypes and explore their application potential for clinical applications.
Most relevant papers
- Larochelle C … Schmidt MHH*, Zipp F* (2018) EGFL7 reduces CNS inflammation in mouse. Nature Comm 9 (1), 819. (*equal contribution, Impact Factor 11.9)
- Jolivel V … Zipp F*, Schmidt MHH* (2015) Perivascular microglia promote blood vessel disintegration in the ischemic penumbra. Acta Neuropathol 129 (2), 279-295. (*equal contribution, Impact Factor 10.8)
- Nikolić I … Schmidt MHH (2013) EGFL7 ligates endothelial αVβ3 integrin to enhance vessel formation. Blood 121 (15), 3041-3050. (Impact Factor 9.8)