Loss of aquaporin-4 results in glymphatic system dysfunction via brain-wide interstitial fluid stagnation.

The glymphatic system is a fluid transport network of cerebrospinal fluid (CSF) entering the brain along arterial perivascular spaces, exchanging with interstitial fluid (ISF), ultimately establishing directional clearance of interstitial solutes. CSF transport is facilitated by the expression of aquaporin-4 (AQP4) water channels on the perivascular endfeet of astrocytes. Mice with genetic deletion of AQP4 (AQP4 KO) exhibit abnormalities in the brain structure and molecular water transport.

Intranasal delivery of growth differentiation factor 5 to the central nervous system.

Context: Growth differentiation factor 5 (GDF5), in addition to its role in bone and joint development, protects dopaminergic (DA) neurons from degeneration, and is a potential therapeutic agent for Parkinson's disease. Its large size and insolubility at physiologic pH are obstacles for drug administration to the central nervous system (CNS) in humans.

Objective: In this study, formulations to deliver GDF5 to the brain using intranasal (IN) administration were developed.

Intranasal deferoxamine provides increased brain exposure and significant protection in rat ischemic stroke.

Deferoxamine (DFO) is a high-affinity iron chelator approved by the Food and Drug Administration for treating iron overload. Preclinical research suggests that systemically administered DFO prevents and treats ischemic stroke damage and intracerebral hemorrhage. However, translation into human trials has been limited, probably because of difficulties with DFO administration.

Intranasal tat alters gene expression in the mouse brain.

Intranasal (IN) delivery of HIV-1 Tat in aging mice was investigated as a possible model for HIV-1 infection in the brain. After IN administration, the distribution of [(125)I]-labeled Tat in the brains of Swiss Webster mice was evaluated by autoradiography and gamma counting. [(125)I]-labeled Tat was detected at the highest concentrations in the olfactory bulb, cervical nodes, and trigeminal nerve tract.