This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We have previously reported that a number of astrocytes can express VCAM-1 and peripherin, an intermediate filament normally found in peripheral neurons. We have also shown that MCP-3 is upregulated close to the blood-brain barrier at the same time. Our hypothesis was that these astrocytes had been activated by viral-infected cells and were a catalyst for the development of encephalitis. Using ex vivo and in vitro models, we examined the timing of increased expression of peripherin in astrocytes, and the concomitant secretion of chemokines. Astrocytes had decreased GFAP expression coincident with increased peripherin. At this time, they were also actively secreting the chemokine MCP-3. This chemokine is important for monocyte migration into brain and the concomitant disruption of the BBB. Thus, MCP-3 is important in neuropathogenesis. It was noted that astrocytes also had increased expression of S100b protein following incubation with SIV infected macrophages. """"""""Cold chase"""""""" studies revealed that astrocytes have the capacity to revert to their native state of low peripherin with high GFAP intermediate filaments and low expression of inflammatory cytokines / chemokines. Thus, the inflammatory stimulus is necessary and sufficient for the production of mediator the leads to BBB disruption. Astrocytes have a plasticity of expression of this and other intermediate filaments. This coincides with the synthesis and secretion of biologically relevant chemokines for the development of encephalitis and disruption of the blood-brain barrier.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000164-50
Application #
8358123
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
50
Fiscal Year
2011
Total Cost
$57,750
Indirect Cost
Name
Tulane University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
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