Monitoring the Response of Hyperbilirubinemia in the Mouse Brain by In Vivo Bioluminescence Imaging.

Isabella Manni, Giuliana Di Rocco, Salvatore Fusco, Lucia Leone, Saviana Antonella Barbati, Carmine Maria Carapella, Claudio Grassi, Giulia Piaggio, Gabriele Toietta

Overview

The study assessed the brain response to hyperbilirubinemia in vivo by non invasive bioluminescence imaging into a mouse model in which light emission is restricted to the regions of active cell proliferation.

Altmetric Statistics

Monitoring the Response of Hyperbilirubinemia in the Mouse Brain by In Vivo Bioluminescence Imaging.

Int J Mol Sci 2016 Dec 28;18(1). Epub 2016 Dec 28.

Department of Research, Advanced Diagnostic, and Technological Innovation, Regina Elena National Cancer Institute, 00144 Rome, Italy.

Increased levels of unconjugated bilirubin are neurotoxic, but the mechanism leading to neurological damage has not been completely elucidated. Innovative strategies of investigation are needed to more precisely define this pathological process. By longitudinal in vivo bioluminescence imaging, we noninvasively visualized the brain response to hyperbilirubinemia in the MITO-Luc mouse, in which light emission is restricted to the regions of active cell proliferation. We assessed that acute hyperbilirubinemia promotes bioluminescence in the brain region, indicating an increment in the cell proliferation rate. Immunohistochemical detection in brain sections of cells positive for both luciferase and the microglial marker allograft inflammatory factor 1 suggests proliferation of microglial cells. In addition, we demonstrated that brain induction of bioluminescence was altered by pharmacological displacement of bilirubin from its albumin binding sites and by modulation of the blood-brain barrier permeability, all pivotal factors in the development of bilirubin-induced neurologic dysfunction. We also determined that treatment with minocycline, an antibiotic with anti-inflammatory and neuroprotective properties, or administration of bevacizumab, an anti-vascular endothelial growth factor antibody, blunts bilirubin-induced bioluminescence. Overall the study supports the use of the MITO-Luc mouse as a valuable tool for the rapid response monitoring of drugs aiming at preventing acute bilirubin-induced neurological dysfunction.

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms18010050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297685PMC
December 2016
151 Reads
2.862 Impact Factor

Publication Analysis

Top Keywords

vivo bioluminescence
8
cell proliferation
8
mito-luc mouse
8
bioluminescence imaging
8
response hyperbilirubinemia
8
bioluminescence
5
brain
5
brain induction
4
demonstrated brain
4
cells addition
4
suggests proliferation
4
factor suggests
4
proliferation microglial
4
microglial cells
4
induction bioluminescence
4
addition demonstrated
4
pharmacological displacement
4
binding sites
4
sites modulation
4
modulation blood-brain
4

References

(Supplied by CrossRef)
The blood–brain barrier and bilirubin encephalopathy
Wennberg et al.
Cell. Mol. Neurobiol. 2000

Similar Publications