Minimally Invasive in Vivo Detection and Tracking of Neuroinflammation via Glia-Derived Exosomes 

Project: Research

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Description

Neuroinflammation is one of important causatives promoting the neuropathogenesis of many neurological diseases, such as Alzheimer disease (AD), Parkinson’s disease (PD), and Multiple Sclerosis (MS), inducing abnormal motor and cognitive functions and behavior. Particularly, in traumatic brain injury (TBI) and spinal cord injury (SCI), neuroinflammation is involved in the nerve degeneration and regeneration. In neuroinfectious diseases, such as Coronavirus associated PD, inflammation is directly induced by the interaction between immune cells and glia cells, such as microglia and astroglia. However, the precise detection of brain inflammation is challenged because of lack of non-invasive biosensing tools and neuroinflammation biomarkers. Recent evidence has demonstrated that exosomes released from neurons and glia in healthy- or diseased- brain can cross the blood–cerebrospinal fluid barrier (BCSFB) and the bloodbrain- barrier (BBB) into the cerebrospinal fluid (CSF) and the circulating blood, supporting the exosomal component from the CSF and the peripheral blood as potential biomarkers to track the molecular and pathological features of parental brain cells. Microglia and astroglia actively control the initiation and progression of neuroinflammation through the release of pro-inflammatory, or anti-inflammatory cytokines and chemokines, therefore, precise label-free detection of inflammation biomarkers in microglia- and astroglia- derived exosomes from the blood and the CSF can be a great biosensing method to dynamically track the inflammatory activity of parent microglia and astroglia in the brain with a time-dependent manner. Analysis of brain-derived exosomes in neurodegenerative diseases has done with RNA seq. and pretomics. However, it is complex, expensive, time-consuming, invasive, and non-translatable. Therefore, minimally invasive and sensitive detection method such as Localized Surface Plasmon Resonance (LSPR) - and Atomic Force Microscopy (AFM)- biosensors can be a simple, cost-effective, precise, sensitive, and translatable method. Label-free quantitative detection of exosomal inflammation biomarkers, such as CD86 and MHCII (M1 microglia-derived exosomes), CD206 and CD163 (M2 microglia-derived exosomes), MHCII (A1 astroglia-derived exosomes), and CD206 (A2 astroglia-derived exosomes), will be very informative to prevent, diagnosis, and treat neuroinflammation present in many neurological disorders as a liquid biopsy. Utilizing mouse models of neuroinflammation, PDGFR-alpha CreERT x MCT1f/f mouse model of chronic neuroinflammation and LPS- induced mouse model of acute neuroinflammation, LSPR and AFM-based detection of inflammation biomarkers in microglia- and astroglia- derived exosomes from the blood and the CSF of the mouse models will be a very effective way for the monitoring of neuroinflammation initiation and progression, and for the testing of the efficacy of drugs in treating neuroinflammation. 

Detail(s)

Project number9043124
Grant typeGRF
StatusActive
Effective start/end date1/01/22 → …