HIV and antiretroviral therapy in the brain: neuronal injury and repair

Ellis, Ronald J.; Langford, Dianne; Masliah, Eliezer; Grant, Igor; Heaton, Robert K.; Wong, Joseph K.; Smith, Davey M; Letendre, Scott; McCutchan, Allen

doi:10.1186/1753-6561-2-s1-s13

Cited by 85 publications

(135 citation statements)

References 141 publications

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“…Neuronal and synaptic damage has been hypothesized to be mediated by neurotoxins derived from activated and infected macrophages that infiltrate the brain (reviewed in (Ellis et al, 2007)). Since brain macrophages are key to the pathogenesis of lentiviral encephalitis, imaging these cells in vivo will enable detection and progression of encephalitis.…”

Section: Discussionmentioning

confidence: 99%

“…Since macrophages are the predominant infected cells in the brain in lentiviral encephailitis (Ellis et al, 2007) Figure 4A) and SIV-infected macrophages ( Figure 4C), but not with GFAP labeled astrocytes ( Figure 4B). Similar results including colocalization of HIV infected cells with [ 3 H]DAA1106 autoradiography were seen in HIVE brain tissues ( Figure 4D).…”

Section: [ 3 H]daa1106 Binding Corresponds To Activated and Infected mentioning

confidence: 99%

“…Deficits observed in these individuals range from minor cognitive impairment, motor and psychiatric dysfunctions to frank dementia thought to result from neuronal damage (Nath et al, 2006). Neuronal and synaptic injury is attributed to viral proteins and toxic products derived from HIV-infected and activated infiltrating macrophages (Ellis et al, 2007). These infected and activated macrophages manifest in the brain as microglial nodules, multinucleated giant cells and perivascular macrophage infiltrates, histopathologically referred to as HIVE.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The high affinity peripheral benzodiazepine receptor ligand DAA1106 binds to activated and infected brain macrophages in areas of synaptic degeneration: Implications for PET imaging of neuroinflammation in lentiviral encephalitis

Venneti

Wang

Wiley

2008

Neurobiology of Disease

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Section: Discussionmentioning

confidence: 99%

Section: [ 3 H]daa1106 Binding Corresponds To Activated and Infected mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The high affinity peripheral benzodiazepine receptor ligand DAA1106 binds to activated and infected brain macrophages in areas of synaptic degeneration: Implications for PET imaging of neuroinflammation in lentiviral encephalitis

Venneti

Wang

Wiley

2008

Neurobiology of Disease

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“…However, most antiretroviral drugs do not penetrate the brain effectively; thereby, HIV can be latently preserved in the CNS, generating an important viral reservoir [reviewed by Ellis et al (2007)]. Several mechanisms are responsible for the restricted movement of many antiretroviral drugs from the circulation into the CNS.…”

Section: Introductionmentioning

confidence: 99%

Intact Lipid Rafts Regulate HIV-1 Tat Protein-Induced Activation of the Rho Signaling and Upregulation of P-Glycoprotein in Brain Endothelial Cells

Zhong

Hennig

Toborek

2009

J Cereb Blood Flow Metab

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The Rho signaling has an essential function in human immunodeficiency virus (HIV)-1-mediated disruption of the integrity of the blood-brain barrier (BBB). However, it is unknown how membrane domains, such as lipid rafts, can influence HIV-1-mediated activation of the Rho pathway and how these processes can affect the expression of the efflux transporters at the BBB level. This study is focused on the function of HIV-1 protein Tat in activation of the Rho signaling and upregulation of P-glycoprotein (P-gp) in human brain endothelial cells. Treatment with Tat markedly elevated GTPRhoA levels and the potential downstream effectors, such as myosin phosphatase target subunit 1 and myosin light chain. In addition, Tat upregulated expression and promoter activity of P-gp as well as its efflux function. Inhibition of the Rho signaling cascade effectively blocked P-gp overexpression at the level of promoter activity. Disruption of lipid rafts by depletion of membrane cholesterol by methyl-beta-cyclodextrin, but not caveolin-1 silencing, also abolished Tat-mediated RhoA activation and P-gp upregulation. The present data indicate the critical function of intact lipid rafts and the Rho signaling in HIV-1-mediated upregulation of P-gp and potential development of drug resistance in brain endothelial cells.

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“…Ellis and colleagues [4,40] found that the historically lowest CD4 count predicts cognitive impairment and is associated with the diagnosis of HAND [41]. ART is considered a positive advancement since it supports and assists the immune system and reduces peripheral viral load; however, there is evidence that the ART used to treat HIV may be responsible for exacerbating common illnesses, especially heart, hepatic, and renal disease [42].…”

Section: Confounding and Complicating Factorsmentioning

confidence: 99%

HIV-Related Neurocognitive Disorders and Drugs of Abuse: Mired in Confound, Surrounded by Risk

Kennedy

Zerbo

2014

Curr Addict Rep

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It has long been known that human immunodeficiency virus (HIV) uses the central nervous system (CNS) as a reservoir and nursery to replicate; therein, it does damage to cells and creates an inflammation that in turn allows for more virus to pass the blood-brain barrier. The inflammatory process itself can cause considerable damage. Neurocognitive disturbance from HIV infection is also known to occur at any stage of the infection. Likewise, common drugs of abuse also have adverse neurocognitive effects on their own. This review examines the literature available to try to elucidate the mechanisms of neurocognitive disorders in the HIV-infected individuals who have used drugs of abuse. Although the incidence of HIV-associated dementia (HAD) has decreased with the advent of highly active anti-retroviral therapy, less severe forms of neurocognitive impairment persist, even with supported immune systems and undetectable viral loads. Considerations for prevention are discussed.

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HIV and antiretroviral therapy in the brain: neuronal injury and repair

Cited by 85 publications

References 141 publications

The high affinity peripheral benzodiazepine receptor ligand DAA1106 binds to activated and infected brain macrophages in areas of synaptic degeneration: Implications for PET imaging of neuroinflammation in lentiviral encephalitis

The high affinity peripheral benzodiazepine receptor ligand DAA1106 binds to activated and infected brain macrophages in areas of synaptic degeneration: Implications for PET imaging of neuroinflammation in lentiviral encephalitis

Intact Lipid Rafts Regulate HIV-1 Tat Protein-Induced Activation of the Rho Signaling and Upregulation of P-Glycoprotein in Brain Endothelial Cells

HIV-Related Neurocognitive Disorders and Drugs of Abuse: Mired in Confound, Surrounded by Risk

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