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PMID: 11414473 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S. Review

Crosstalk between components of the blood brain barrier and cells of the CNS in microglial activation in AIDS.

Brain pathology (Zurich, Switzerland) ·Vol. 11 ·No. 3 ·2001-07-00 ·Pages 306-12

Langford D, Masliah E

Abstract

During the progression of AIDS, a majority of patients develop cognitive disorders such as HIV encephalitis (HIVE) and AIDS dementia complex (ADC), which correlate closely with macrophage infiltration into the brain and microglial activation. Microglial activation occurs in response to infection, inflammation and neurological disorders including HIVE, Alzheimer's disease, Parkinson's disease and multiple sclerosis. Microglia can be activated by immunoreactive cells independent of, but enhanced by HIV infection, from at least two routes. Activation may occur from signals originating from activated monocytes and lymphocytes in the blood stream, which initiate a cascade of stimuli that ultimately reach microglia in the brain or from activated macrophages/microglia/astrocytes within the brain. Effects of microglial activation stemming from both systemic and CNS HIV infection act together to commence signaling feedback, leading to HIVE and increased neurodegeneration. Most recent data indicate that in AIDS patients, microglial activation in the brain with subsequent release of excitotoxins, cytokines and chemokines leads to neurodegeneration and cognitive impairment. Since the presence of HIV in the brain results from migration of infected monocytes and lymphocytes across the vascular boundary, the development of novel therapies aimed at protecting the integrity of the blood brain barrier (BBB) upon systemic HIV infection is critical for controlling CNS infection.

MeSH Terms
AIDS Dementia Complex/metabolism,pathology Acquired Immunodeficiency Syndrome/metabolism,pathology Astrocytes/physiology Blood-Brain Barrier/physiology Chemotaxis, Leukocyte Cytokines/physiology Endothelium, Vascular/pathology Feedback Gene Products, tat/physiology HIV/physiology Humans Lymphocytes/virology Macrophage Activation Microglia/metabolism,pathology Monocytes/virology Nerve Degeneration/virology Signal Transduction tat Gene Products, Human Immunodeficiency Virus
Chemicals
Cytokines Gene Products, tat tat Gene Products, Human Immunodeficiency Virus
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Langford D
Department of Neurosciences, University of California San Diego, La Jolla 92093, USA.
Masliah E
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Article Info
Journal
Brain pathology (Zurich, Switzerland)
Abbr.
Brain Pathol
ISSN
1015-6305
DOI
10.1111/j.1750-3639.2001.tb00401.x
Published
2001-07-00
Pages
306-12
Language
English
Region
Switzerland
NLM ID
9216781
PMCID
PMC8098377
Subset
IM
Grants
NIDA NIH HHS · DA12065 · United States
NIMH NIH HHS · MH45294 · United States
NIMH NIH HHS · MH59745 · United States
External Links
PubMed source DOI: 10.1111/j.1750-3639.2001.tb00401.x PMC Full Text View journal details
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