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Chemokines may play a role in leukocyte migration across the blood-brain barrier (BBB) during neuroinflammation and other neuropathological processes, such as epilepsy. We investigated the role of the chemokine receptor CCR5 in seizures. We used a rat model based on intraperitoneal kainic acid (KA) administration. Four months before KA injection, adult rats(More)
Gene transfer to the central nervous system (CNS) has been approached using various vectors. Recombinant SV40-derived vectors (rSV40s) transduce neurons and microglia effectively in vitro, so we tested rSV40s gene transfer to the CNS in vivo, and characterized the distribution, duration and cell types transduced. We used rSV40s carrying Human(More)
CCR3 has been implicated as a co-receptor for human immunodeficiency virus type 1 (HIV-1), particularly in brain microglia cells. We sought to clarify the comparative roles of CCR3 and CCR5 in the central nervous system (CNS) HIV-1 infection and the potential utility of CCR3 as a target for manipulation via gene transfer. To target CCR3, we developed a(More)
Human immunodeficiency virus-1 (HIV-1) infection in the central nervous system (CNS) may lead to neuronal loss and progressively deteriorating CNS function: HIV-1 gene products, especially gp120, induce free radical-mediated apoptosis. Reactive oxygen species (ROS), are among the potential mediators of these effects. Neurons readily form ROS after gp120(More)
Blood-brain barrier (BBB) disruption occurs during human immunodeficiency virus encephalopathy, but the mechanisms involved are not understood. We studied how acute and ongoing exposure to human immunodeficiency virus 1 envelope gp120 alters BBB structure and permeability. Intravenous Evans blue, given before stereotaxic gp120 injection into the caudate(More)
HIV-associated neurocognitive disorder (HAND) is an increasingly common, progressive disease characterized by neuronal loss and progressively deteriorating CNS function. HIV-1 gene products, particularly gp120 and Tat elicit reactive oxygen species (ROS) that lead to oxidant injury and cause neuron apoptosis. Understanding of, and developing therapies for,(More)
Matrix metalloproteinases (MMPs) are implicated in diverse processes, such as neuroinflammation, leakiness of the blood-brain barrier (BBB) and direct cellular damage in neurodegenerative and other CNS diseases. Tissue destruction by MMPs is regulated by their endogenous tissue inhibitors (TIMPs). TIMPs prevent excessive MMP-related degradation of(More)
We examined the role of reactive oxygen species (ROS) in loss of dopaminergic neurons (DNs) from the substantia nigra (SN) in neuroAIDS. The frequency of Parkinson-like symptomatology, and DN loss, in neuroAIDS is often attributed to nonspecific DN fragility to oxidative stress. Cultured DN are more sensitive to ROS than non-dopaminergic neurons (RN): DN(More)
Human immunodeficiency virus-1 (HIV-1) is the most frequent cause of dementia in adults under 40. We sought to use gene delivery to protect from HIV-1-related neuron loss. Because HIV-1 envelope (Env) gp120 elicits oxidant stress and apoptosis in cultured neurons, we established reproducible parameters of Env-mediated neurotoxicity in vivo, then tested(More)
HIV-1 gp120 neurotoxicity and oxidant injury are well documented, but consequent neuroinflammation is less understood. Rat caudate-putamens (CPs) were challenged with 100-500 ng HIV-1BaL gp120, with or without prior rSV40-delivered superoxide dismutase or glutathione peroxidase. CD11b-positive microglia were increased 1 day post-challenge; Iba-1- and(More)