In vivo longitudinal visualization of the brain neuroinflammatory response at the cellular level in LysM-GFP mice induced by 3-nitropropionic acid

Abstract

Blood-brain barrier (BBB) dysfunction is related to the development of neuroinflammation in the central nervous system (CNS). Neuroinflammation has been implicated as one of the key factors in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease. Despite its importance, the impacts and underlying cellular mechanisms of chronic BBB impairment in neurodegenerative diseases are poorly understood. In this work, we performed a longitudinal intravital brain imaging of mouse model with neuroinflammation induced by 3-nitropropionic acid (3-NP). For this, we obtained a transgenic LysM-GFP mouse expressing the green fluorescence protein (GFP) in a subset of leukocytes. By using intravenously injected fluorescence blood tracers, we longitudinally observed in vivo dynamic cellular behaviors and the BBB integrity through a 30-day neuroinflammatory state. Vascular leakages in the cerebral cortex reflecting BBB impairment were observed at two weeks, which persisted to the third week, followed by a severe inflammatory response with massive leukocytes infiltration at day 30. These descriptions can help in the development of novel approaches to treat neurodegenerative conditions.