Astrocytic Network Functions in a Cerebral Microinfarct Model

Andrea Delekate1, Gabor Petzold2

1 Neurovascular Diseases Lab, DZNE Bonn
2 Neurovascular Diseases Lab, DZNE Bonn; Division of Vascular Neurology Dpt. of Neurology, University Hospital Bonn

Cerebral microinfarcts are microscopic ischemic lesions consisting of a small necrotic core that is sharply delineated by astrocytic and microglial gliosis. Microinfarcts are difficult to detect with conventional clinical imaging methods, but microscopically they can be commonly found in a widespread area throughout the aging brain. Importantly, they appear to be a crucial and independent vascular factor contributing to neurodegeneration, brain atrophy and cognitive impairment. However, the exact pathways by which microinfarcts lead to cognitive decline have remained unclear.

We established a mouse model of cerebral microinfarcts by endovascular injections of fluorescent microspheres that block penetrating arterioles with a diameter of 20-27 µm. With this model we were able to recapitulate histopathological findings from human post-mortem tissue.
To assess cellular changes especially at the neurovascular unit we performed acute and chronic in vivo imaging experiments of astrocytic calcium activity in anesthetised as well as awake animals that underwent microinfarct surgeries. Initial results point to an increased astrocytic calcium activity in animals that were subjected to microinfarcts.
Furthermore, we induced microinfarcts in an animal model of Alzheimer’s disease and are investigating to what extent pathological changes are aggravated when both pathologies are present.