Aquaporin-4 mediates blood brain barrier permeability during endotoxemia

Aquaporin-4 (AQP4) is a water channel expressed on astrocytes known to regulate the exchange of fluids and solutes between the parenchyma of the central nervous system (CNS) and perivascular spaces. We hypothesized that activation of AQP4 may mediate permeability of the CNS during systemic inflammation. Here, mice were i.v. injected with fluorescent tracers of low (1 kd) and intermediate (10 kd) molecular weights 24 hours after induction of endotoxemia with i.p. LPS. Fluorescent microscopy using tissue sections and cleared half-brains showed that endotoxemia increased tracer penetrance into the brain parenchyma. Temporal and spatial distribution of tracers suggested that penetrance occurred across neurovasculature, choroid plexus, and circumventricular organs (CVOs). Treatment with the AQP4 inhibitor, AER-271, blocked tracer passage across the glia limitans and caused tracer accumulation within perivascular spaces. These data show that AQP4 mediates the flux of solutes from the perivascular space to the brain parenchyma during systemic inflammation and highlight a novel strategy to neuroprotection during sepsis.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Animal Sciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2022

Author dc:creator

• Gonzalez Ricon, Rafael Jaime

Contributors dc:contributor

• McKim, Daniel Boyce
• Rhodes, Justin
• Raetzman, Lori

• AQP4
• Sepsis
• Blood brain barrier (BBB).

Statement dc:rights

• Copyright 2021 Rafael Jaime Gonzalez Ricon

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/112977

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/112977