Neuroanatomical Tract Tracers: Not Just for Neural Tracing Anymore

Abstract

Neuroanatomical tract tracers (NaTTs) have been used for neural circuit tracing for decades and now find recent applications in disease diagnosis and drug and gene delivery. In this Review, first the different subclasses of NaTTs including nonviral and viral types and their unique properties are discussed. The focus then is shifted to recent developments in improving the design and performance of NaTTs for neural circuit mapping, their role in disease diagnostics, and the emerging applications in drug and gene delivery targeted to the nervous system. In contrast to most molecular and biologic drugs that do not pass through the blood−brain barrier, NaTTs, including certain types of plant lectins, bacterial toxins, and some viruses, are readily taken up by nerve endings in mammalian muscle and efficiently transported within the central nervous system to the brain. Incorporating NaTTs into nanomedicines to bypass biological barriers and to deliver drugs to specific neurons thus presents an exciting direction and offers many possibilities for drug delivery. We hope that this Review will catalyze further discussions and collaborations among neuroscientists, biomedical researchers, and nanotechnologists that lead to innovative therapeutic options for treating neurological diseases.

Fluorescence imaging of peripheral nerve function and structure

“…These tracers can be locally injected to achieve fluorescence labeling of nerve fibers. Since several great reviews summarizing work on viral tracers have been published recently, 36–38 this section in our review will simply list and discuss some of the most commonly utilized virus-related tracers.…”

Real time monitoring peripheral nerve function with ICG and BDA-ICG by NIR-II fluorescence imaging

“…Owing to these distinct benefits, fluorescence imaging has found extensive applications in the diagnosis of diseases, evaluation of drug distribution and metabolism, and image-guided precision surgery [ 5 , 6 ]. There have been many fluorescent tracers used in neuroanatomical tracing to study the complex interconnections of the nervous system, including fluorescent dyes (carbocyanine, rhodamine, fast blue) and fluorescent compounds (dextran molecules, biotinylated dextran amines) [ 7 ]. In our previous studies, carbonized polymer dots and Au nanodots were conjugated with Cholera toxin B (CTB) or biotinylated dextran amine (BDA, an anterograde neural tracer which produces sensitive and detailed labelling) to make novel fluorescent neural tracers with significant advantages, such as excellent optical properties, physiochemical stability, and biocompatibility [ [8] , [9] , [10] ].…”