Intravital imaging of immune response and cerebrovascular alteration in the pathogenesis of neurodegenerative disease

Abstract

Neurodegenerative diseases include Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and so on, and induce cognitive and behavior impairments. However, cellular-level dynamics at the onset of neuro-logical disease is poorly understood because of the technical limitation. Herein, our custom-built video-rate laser-scanning confocal microscopy system allowed to spatiotemporally visualize cerebral cortex in vivo though brain imaging window, and to investigate immune response and cerebrovascular alteration in the pathogenesis of chronic neuroinflammation and cerebral microinfarction model.

We successfully established a chronic neuroinflammation model, which is detected at the onset of neuro-degenerative disease, using 3-nitropropionic acid and performed a 30-day longitudinal intravital imaging of immune response and the alteration of blood-brain barrier in meninges and cerebral cortex.

We performed a 30-day longitudinal intravital imaging of cerebral microinfarct formation after inducing an acute focal ischemic damage in cerebral cortex. Astrocytes, pericytes and endothelial cells, which compose neurovascular unit, were visualized in vivo at same time, and the imaging data showed that a partial recovery of pericytes and endothelial cells restored blood flow from the blocked blood flow after the ischemic damage. On the other hand, an astrocyte reactivity, such as an increase of astrocyte soma size and a glial fibrillary acidic protein (GFAP) expression, highly increased at the peri-infarct area and was associated with a massive collagen deposition in the peri-infarct, resulting from glial scar formation. Furthermore, an administration of a reversible monoamine oxidase B (MAO-B) inhibitor suppressed astrocyte reactivity at the peri-infarct, lead-ing to decrease the collagen deposition in the microinfarct.