Extending the glymphatic system beyond the brain: The Cochlear aqueduct as a neuroimmune gateway to the inner ear.

The cochlear aqueduct, located within the temporal bone, forms a narrow connection between the cerebrospinal fluid (CSF) in the subarachnoid space and the perilymph of the scala tympani in the inner ear. The anatomical linkage provides a potential interface for pressure regulation, molecular exchange, and therapeutic access to the cochlea. Recent findings further indicate that the cochlear aqueduct is functionally coupled to the brain's glymphatic system, permitting CSF flow to the inner ear and raising the possibility of an inner ear glymphatic system. Morphological studies demonstrate substantial interspecies variability in cochlear aqueduct size and patency among species, and identified a diaphragm-like terminal membrane at its lateral end. In mice, immunocytochemical analyses indicate a lymphatic-like phenotype reminiscent of the subarachnoid lymphatic-like membrane (SLYM). The presence of macrophages with phagocytic capacity and the fact that the membrane is activated during bacterial meningitis further supports a role in local immune surveillance. The translational relevance of the cochlear aqueduct has gained attention with advances in inner-ear gene therapy. Tracers injected in cisterna magna in mice reach the inner ear rapidly. In rodents and non-human primates, intracisternal injection of viral vectors via achieves efficient bilateral cochlear transduction, including restoration of hearing in VGLUT3-deficient mice, a model of nonsyndromic deafness. These findings position the cochlear as a minimally invasive route for inner-ear therapy, potentially avoiding direct cochlear surgery. However, interspecies differences and age-related changes in cochlear aqueduct patency must be carefully evaluated before clinical translation.