Cervical Lymph Duct-Cannulated Rat Model for Assessing Lymphatic Transport from the Head and Brain

Lymph flows from the central nervous system (CNS) via a series of lymphatic vessels (LVs) and lymph nodes that converge at the cervical lymph ducts. In addition to maintaining fluid balance, these lymphatic ducts play a key role in transporting a wide array of substances, including endogenous metabolites, signaling molecules, immune cells, and small and macromolecular drugs. This is critical for physiological homeostasis and immune function in both intracranial (e.g., brain) and extracranial regions (e.g., nasal and oral cavities). Impaired lymphatic drainage from the brain has increasingly been linked to a range of neurological and neurodegenerative disorders. Cervical lymph duct cannulation enables the collection of lymph draining the head and brain, allowing the measurement of the concentration and transport rate of various substances via the lymphatic system. Changes in these factors in response to different challenges (e.g., drugs, stress, trauma) and diseases (e.g., stroke, infection, Alzheimer's disease) can also be determined. Here, we describe an anesthetized, deep cervical lymph duct cannulated rat model that enables lymph collection for several hours following surgery. The method may be combined with imaging and multi-omics technologies for the measurement of a wide range of parameters of interest in the lymph. This facilitates fundamental physiological and pathophysiological research of the head and neck region, as well as pharmacokinetic/pharmacodynamic studies of drugs, particularly for the treatment of CNS diseases.