Human Immunodeficiency Virus-Associated Dementia: An Evolving Disease

McArthur, Justin C.; Haughey, Norman J.; Gartner, Suzanne; Conant, Kathy; Pardo, Carlos A.; Nath, Avi; Sacktor, Ned

doi:10.1080/13550280390194109

Cited by 361 publications

(284 citation statements)

References 127 publications

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“…Recent concern about the consequences of HAD has emerged with the increasing resistance to antiretroviral drugs. With introduction of HAART, therefore, the patients on HAART with a slowly progressive dementia and incomplete virological control have been proposed (McArthur et al, 2003). Recently, Brenchley et al reported that plasma LPS levels are still higher in chronic HIV-infected patients with HAART than in the uninfected (Brenchley et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide-enhanced transcellular transport of HIV-1 across the blood-brain barrier is mediated by the p38 mitogen-activated protein kinase pathway

Dohgu

Banks

2008

Experimental Neurology

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Chronic systemic inflammation in the late stage of human immunodeficiency virus type-1 (HIV-1) infection could increase neuroinvasion of infected monocytes and cell-free virus, causing an aggravation of neurological disorders in AIDS patients. We previously showed that the peripheral administration of lipopolysaccharide (LPS) enhanced the uptake across the blood-brain barrier (BBB) of the HIV-1 viral protein gp120. Brain microvessel endothelial cells are targets of LPS. Here, we investigated whether the direct interaction between LPS and the BBB also affected HIV-1 transport using primary mouse brain microvessel endothelial cells (BMECs). LPS produced a dose (1-100 μg/mL)-and time (0.5-4 hr)-dependent increase in HIV-1 transport and a decrease in transendothelial electrical resistance (TEER). Whereas indomethacin (cyclooxygenase inhibitor) and L-NAME (NO synthase inhibitor) did not affect the LPS-induced changes in HIV-1 transport or TEER, pentoxifylline (TNF-αinhibitor) attenuated the decrease in TEER induced by LPS, but not the LPSinduced increase in HIV-1 transport. LPS also increased the phosphorylation of p44/42 MAPK and p38 MAPK but not that of JNK. U0126 (p44/42 MAPK inhibitor) and SP600125 (JNK inhibitor) did not inhibit the LPS-induced increase in HIV-1 transport although U0126 attenuated the reduction in TEER. SB203580 (p38 MAPK inhibitor) inhibited the LPS-induced increase in HIV-1 transport without affecting TEER. Thus, LPS-enhanced HIV-1 transport is independent of changes in TEER and so is attributed to increased transcellular trafficking of HIV-1 across the BBB. These results show that LPS increases HIV-1 transcellular transport across the BBB by a pathway that is mediated by p38 MAPK phosphorylation in BMECs.

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Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide-enhanced transcellular transport of HIV-1 across the blood-brain barrier is mediated by the p38 mitogen-activated protein kinase pathway

Dohgu

Banks

2008

Experimental Neurology

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“…With increased life expectancy, the prevalence of HIV-associated cognitive and neurological impairment is actually rising despite highly active antiretroviral therapy. 5,6 A number of therapeutic agents have been tried to target pathological sequelae of HIV neurological infection, ranging from the pain associated with peripheral neuropathology to neuron dysfunction and death, but few have been approved for clinical use. Thus, it is necessary to explore alternative strategies for treating HIV-associated neurological diseases.…”

Section: Human Immunodeficiency Virus (Hiv)-1 Tat Protein Ismentioning

confidence: 99%

Protection against Human Immunodeficiency Virus Type 1 Tat Neurotoxicity by Ginkgo biloba Extract EGb 761 Involving Glial Fibrillary Acidic Protein

Zou

Kim

Zhou

et al. 2007

The American Journal of Pathology

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Human immunodeficiency virus (HIV)-1 Tat protein isan important pathogenic factor in HIV-associated neuropathogenesis. Despite recent progress, the molecular mechanisms underlying Tat neurotoxicity are still not completely understood. However, few therapeutics have been developed to specifically target HIV infection in the brain. Recent development of an inducible brain-specific Tat transgenic mouse model has made it possible to define the mechanisms of Tat neurotoxicity and evaluate anti-neuroAIDS therapeutic candidates in the context of a whole organism. Herein, we demonstrate that administration of EGb 761, a standardized formulation of Ginkgo biloba extract, markedly protected Tat transgenic mice from Tat-induced developmental retardation, inflammation, death, astrocytosis, and neuron loss. EGb 761 directly down-regulated glial fibrillary acidic protein (GFAP) expression at both protein and mRNA levels. This down-regulation was, at least in part, attributable to direct effects of EGb 761 on the interactions of the AP1 and NF-B transcription factors with the GFAP promoter. Most strikingly, Tat-induced neuropathological phenotypes including macrophage/microglia activation, central nervous system infiltration of T lymphocytes, and oxidative stress were significantly alleviated in GFAP-null/Tat transgenic mice. Taken together, these results provide the first evidence to support the potential for clinical use of EGb 761 to treat HIV-associated neurological diseases. Moreover, these findings suggest for the first time that GFAP activation is directly involved in Tat neurotoxicity, supporting the notion that astrocyte activation or astrocytosis may directly contribute to HIV-associated neurological disorders.

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“…Graus menores de dano cognitivo, motor e funcional, na qual não são suficientes para o diagnóstico de demência é chamado transtorno cognitivo-motor menor associado-HIV e nem sempre pacientes com estes transtornos evoluem para franca demência 5 .…”

Section: Diagnóstico Das Alterações Cognitivas Da Aidsunclassified

“…Portanto é importante reconhecer precocemente danos sutis, já que, em alguns casos, podem significativamente melhorar a chance de reversão da demência com HAART 5 , melhorar a qualidade de vida com tratamentos adicionais 46 e mesmo possibilitar a monitorização da aderência do paciente à medicação. Além do fato de poder melhorar a orientação para os familiares sobre as alterações comportamentais e cognitivas do paciente.…”

Section: Diagnóstico Das Alterações Cognitivas Da Aidsunclassified

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Alterações cognitivas na infecção pelo HIV e Aids

Christo¹

2010

Rev. Assoc. Med. Bras.

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Human Immunodeficiency Virus-Associated Dementia: An Evolving Disease

Abstract: This article reviews the changing epidemiology of HIV-associated dementia, current concepts of the different patterns of dementia under the influence of highly active antiretroviral therapy, and reviews therapeutic aspects.

Cited by 361 publications

References 127 publications

Lipopolysaccharide-enhanced transcellular transport of HIV-1 across the blood-brain barrier is mediated by the p38 mitogen-activated protein kinase pathway

Lipopolysaccharide-enhanced transcellular transport of HIV-1 across the blood-brain barrier is mediated by the p38 mitogen-activated protein kinase pathway

Protection against Human Immunodeficiency Virus Type 1 Tat Neurotoxicity by Ginkgo biloba Extract EGb 761 Involving Glial Fibrillary Acidic Protein

Alterações cognitivas na infecção pelo HIV e Aids

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