Increased activity of matrix metalloproteinases in the cerebrospinal fluidof patients with HIV-associated neurological diseases

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 zymog raphy in the cerebrospinal fluid (CSF) of 138 HIV-infected patients (40 wit h AIDS dementia, 83 with brain opportunistic infections and 15 neurological ly asymptomatic), 26 HIV-seronegative individuals with inflammatory neurolo gical 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 fr om HIV-infected patients, including those with HIV dementia, central nervou s system (CNS) opportunistic infections or neurologically asymptomatic subj ects, The highest levels of MMP-9 were found in the CSF of patients with cr yptococcosis, cytomegalovirus encephalitis and tuberculous meningitis and w ere comparable with those found in the CSF of HIV-negative patients with mu ltiple 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 ext racellular matrix of blood-brain barrier may contribute to the transendothe lial migration of virus-infected cells into the CNS and development of HIV- associated neurologic damage.