Aquaporin-4 mediates blood brain barrier permeability during endotoxemia

Gonzalez Ricon, Rafael Jaime

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https://hdl.handle.net/2142/112977 Copy

Description

Title

Aquaporin-4 mediates blood brain barrier permeability during endotoxemia

Author(s)

Gonzalez Ricon, Rafael Jaime

Issue Date

2021-07-01

Director of Research (if dissertation) or Advisor (if thesis)

McKim, Daniel Boyce

Committee Member(s)

• Rhodes, Justin
• Raetzman, Lori

Department of Study

Animal Sciences

Discipline

Animal Sciences

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

M.S.

Degree Level

Thesis

Keyword(s)

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

Abstract

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.

Graduation Semester

2021-08

Type of Resource

Thesis

Permalink

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

Copyright and License Information

Copyright 2021 Rafael Jaime Gonzalez Ricon

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