University of Illinois Urbana-Champaign

Aquaporin-4 mediates blood brain barrier permeability during endotoxemia

Gonzalez Ricon, Rafael Jaime

Content Files
GONZALEZRICON-THESIS-2021.pdf

Permalink

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

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
Date of Ingest
2022-01-12T21:45:23Z
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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Graduate Dissertations and Theses at Illinois PRIMARY
Graduate Theses and Dissertations at Illinois
Dissertations and Theses - Animal Sciences