Lokesh Agrawal

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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-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)
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)
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)
Toxicity of HIV-1 envelope glycoprotein (gp120) for substantia nigra (SN) neurons may contribute to the Parkinsonian manifestations often seen in HIV-1-associated dementia (HAD). We studied the neurotoxicity of gp120 for dopaminergic neurons and potential neuroprotection by antioxidant gene delivery. Rats were injected stereotaxically into their(More)
HIV-1 effects on the blood-brain barrier (BBB) structure and function are still poorly understood in animal models based on direct administration of recombinant HIV proteins. We therefore injected HIV-1 envelope glycoprotein, gp120, into rat caudate-putamens (CPs) and examined vascular integrity and function. Gp120 coimmunostained with endothelial cell(More)
Caspases are implicated in neuronal death in neurodegenerative and other central nervous system (CNS) diseases. In a rat model of human immunodeficiency virus type 1 (HIV-1) associated neurocognitive disorders (HAND), we previously characterized HIV-1 envelope gp120-induced neuronal apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling(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)
Human immunodeficiency virus 1 (HIV-1) encephalopathy is thought to result in part from the toxicity of HIV-1 envelope glycoprotein gp120 for neurons. Experimental systems for studying the effects of gp120 and other HIV proteins on the brain have been limited to the acute effects of recombinant proteins in vitro or in vivo in simian immunodeficiency(More)
We and others have identified luteinizing hormone-releasing hormone (LHRH) in cells of the immune system in both animals and humans. LHRH is an immunostimulant, and testosterone is an immunosuppressant. Because testosterone is known to modulate the concentrations of hypothalamic LHRH, we wondered whether testosterone might also alter the concentrations of(More)