Abstract
Matrix metalloproteinases (MMPs) have been identified as mediators of brain injury in HIV-associated neurological diseases. The activity of the 72 kDa gelatinase A (MMP-2) and 92 kDa gelatinase B (MMP-9) was detected by zymography in the cerebrospinal fluid (CSF) of 138 HIV-infected patients (40 with AIDS dementia, 83 with brain opportunistic infections and 15 neurologically asymptomatic), 26 HIV-seronegative individuals with inflammatory neurological diseases (IND) and 12 HIV-seronegative subjects with noninflammatory neurological diseases (NIND). MMP-2 was present in all CSF samples from HIV-seropositive and HIV-seronegative individuals, including those of subjects with NIND. On the contrary, MMP-9 was absent in the CSF of NIND controls, whereas the activity of this MMP was found in the 77 - 100% of CSF samples from HIV-infected patients, including those with HIV dementia, central nervous system (CNS) opportunistic infections or neurologically asymptomatic subjects. The highest levels of MMP-9 were found in the CSF of patients with cryptococcosis, cytomegalovirus encephalitis and tuberculous meningitis and were comparable with those found in the CSF of HIV-negative patients with multiple sclerosis or meningitis. A significant correlation between CSF MMP-9 activity and CSF cell count was found only in patients with HIV dementia. The increased CSF activity of MMPs capable to degrade components of the extracellular matrix of blood-brain barrier may contribute to the transendothelial migration of virus-infected cells into the CNS and development of HIV-associated neurologic damage.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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AIDS Dementia Complex / cerebrospinal fluid*
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AIDS Dementia Complex / enzymology
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AIDS-Related Opportunistic Infections / cerebrospinal fluid*
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AIDS-Related Opportunistic Infections / enzymology
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Adolescent
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Adult
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Blood-Brain Barrier
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CD4 Lymphocyte Count
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Cell Count
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Cell Movement
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Cerebrospinal Fluid / cytology
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Cerebrospinal Fluid Proteins / analysis*
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Child
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Child, Preschool
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Cytomegalovirus Infections / cerebrospinal fluid
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Cytomegalovirus Infections / enzymology
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Disease Progression
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Encephalitis, Viral / cerebrospinal fluid
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Encephalitis, Viral / enzymology
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Female
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HIV Infections / cerebrospinal fluid*
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HIV Infections / enzymology
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HIV Seronegativity
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HIV-1*
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Humans
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Male
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Matrix Metalloproteinase 2 / biosynthesis
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Matrix Metalloproteinase 2 / cerebrospinal fluid*
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Matrix Metalloproteinase 2 / genetics
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Matrix Metalloproteinase 9 / biosynthesis
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Matrix Metalloproteinase 9 / cerebrospinal fluid*
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Matrix Metalloproteinase 9 / genetics
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Meningitis, Bacterial / cerebrospinal fluid
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Meningitis, Bacterial / enzymology
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Meningitis, Cryptococcal / cerebrospinal fluid
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Meningitis, Cryptococcal / enzymology
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Middle Aged
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Motor Neuron Disease / cerebrospinal fluid
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Motor Neuron Disease / enzymology
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Multiple Sclerosis / cerebrospinal fluid
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Multiple Sclerosis / enzymology
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Nervous System Diseases / cerebrospinal fluid*
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Nervous System Diseases / enzymology
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Toxoplasmosis, Cerebral / cerebrospinal fluid
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Toxoplasmosis, Cerebral / enzymology
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Tuberculosis, Meningeal / cerebrospinal fluid
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Tuberculosis, Meningeal / enzymology
Substances
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Cerebrospinal Fluid Proteins
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9