Live Mapping of the Brain Extracellular Matrix and Remodeling in Neurological Disorders

Live imaging of the brain extracellular matrix (ECM) provides vital insights into changes that occur in neurological disorders. Current techniques such as second or third-harmonic generation offer limited contrast for live imaging of the brain ECM. Here, a new method, pan-ECM via chemical labeling of extracellular proteins, is introduced for live brain ECM imaging. pan-ECM labels all major ECM components in live tissue including the interstitial matrix, basement membrane, and perineuronal nets. pan-ECM enables in vivo observation of the ECM heterogeneity between the glioma core and margin, as well as the assessment of ECM deterioration under stroke condition, without ECM shrinkage from tissue fixation. These findings indicate that the pan-ECM approach is a novel way to image the entire brain ECM in live brain tissue with optical resolution. pan-ECM has the potential to advance the understanding of ECM in brain function and neurological diseases. A novel approach, pan-ECM, is introduced to live imaging of the brain extracellular matrix (ECM) in the brain, which is previously challenging to observed in live tissue with conventional imaging methods. The method utilizes a non-aggregated and protein-reactive dye to bind proteins in the ECM, achieving homogenous labeling on brain ECM compartments, such as presented on the interstitial matrix, basement, and perineuronal nets.image