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PMID: 11240016 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Reduction in glial immunity and neuropathology by a PAF antagonist and an MMP and TNFalpha inhibitor in SCID mice with HIV-1 encephalitis.

Journal of neuroimmunology ·Vol. 114 ·No. 1-2 ·2001-03-01 ·Pages 57-68

Persidsky Y, Limoges J, Rasmussen J, Zheng J, Gearing A, Gendelman HE

Abstract

The effects of anti-inflammatory drugs on glial immunity and neuropathology were determined in a severe combined immune deficiency (SCID) mouse model of HIV-1 encephalitis. HIV-1-infected human monocyte-derived macrophages (MDM) are stereotactically inoculated into basal ganglia resulting in a multinucleated giant cell encephalitis. A platelet activating factor antagonist and a matrix metalloproteinase inhibitor, which also inhibits tumor necrosis factor alpha release, were administered to animals at the time of the MDM inoculation. The drugs administered in combination markedly reduced brain inflammation, astrogliosis and microglia activation. These findings demonstrate that reduction of brain inflammatory responses, independent of viral replication, can affect HIVE pathology in an animal model system of disease.

MeSH Terms

AIDS Dementia Complex/drug therapy,immunology Animals Benzyl Compounds Cell Survival/immunology Dexamethasone/pharmacology Disease Models, Animal Drug Combinations Gliosis/immunology HIV-1 Humans In Vitro Techniques Interleukin-1/metabolism Interleukin-8/metabolism Leucine/analogs & derivatives,pharmacology Macrophages/immunology,metabolism Male Matrix Metalloproteinase 2/metabolism Matrix Metalloproteinase 9/metabolism Matrix Metalloproteinase Inhibitors Mice Mice, SCID Microglia/immunology,pathology,virology Neurons/immunology,pathology Pentoxifylline/pharmacology Platelet Activating Factor/antagonists & inhibitors,biosynthesis Protease Inhibitors/pharmacology Succinates Transforming Growth Factor beta/metabolism Tumor Necrosis Factor-alpha/antagonists & inhibitors,biosynthesis

Chemicals

BB 1101 BB 882 Benzyl Compounds Drug Combinations Interleukin-1 Interleukin-8 Matrix Metalloproteinase Inhibitors Platelet Activating Factor Protease Inhibitors Succinates Transforming Growth Factor beta Tumor Necrosis Factor-alpha Dexamethasone Matrix Metalloproteinase 2 Matrix Metalloproteinase 9 Leucine Pentoxifylline

Authors & Affiliations

6 authors, click to expand affiliations / ORCID

Persidsky Y

The Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, 985215 Nebraska Medical Center, Omaha, NE 68198-5215, USA. ypersids@unmc.edu

Limoges J

Rasmussen J

Zheng J

Gearing A

Gendelman H E

Article Info

Journal

Journal of neuroimmunology

Abbr.

J Neuroimmunol

ISSN

0165-5728

DOI

10.1016/s0165-5728(00)00454-9

ypersids@unmc.edu

Published

2001-03-01

Pages

57-68

Language

English

Region

Netherlands

NLM ID

8109498

Subset

Grants

NIMH NIH HHS · K08 MH01552-01A1 · United States

NINDS NIH HHS · P01NS31492-01 · United States

NINDS NIH HHS · R01NS34239-01 · United States

NINDS NIH HHS · R01NS34239-02 · United States

NINDS NIH HHS · R01NS36126-01 · United States

NIAID NIH HHS · R29 AI42404-02 · United States

External Links

PubMed source DOI: 10.1016/s0165-5728(00)00454-9 View journal details

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Reduction in glial immunity and neuropathology by a PAF antagonist and an MMP and TNFalpha inhibitor in SCID mice with HIV-1 encephalitis.

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