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To investigate the effect of cerebrospinal fluid (CSF) of HIV-1-seropositive patients with and without HIV-1-associated dementia complex (HADC) on the intracellular Ca2+ regulation of cultured cortical astrocytes.In a blinded study the effects of CSF samples from HADC patients and from HIV-1-seropositive but not demented patients on intracellular Ca2+ regulation of cultured cortical astrocytes were investigated. Astrocytes were chosen because they contribute to both electrophysiological and immunological processes within the brain.Astrocytes were incubated in CSF samples for 1 h, loaded with the Ca2+ indicator dye Fura-2 and intracellular Ca2+ responses upon glutamate application were measured.CSF samples from 10 out of 11 HADC patients induced a significant reduction of the intracellular Ca2+ increase upon glutamate application. On the contrary, seven out of 10 CSF samples from HIV-1-seropositive patients without HADC as well as 10 out of 10 CSF samples from HIV-1-seronegative controls did not affect the intracellular Ca2+ response.Our data strongly confirm the hypothesis that CSF samples of HADC patients contain soluble factors which interfere with the function of astrocytes. These factors may include HIV-1 proteins, locally released cytokines or neurotoxins.