HIV-1-Associated Dementia

Keywords HTV infection dementia antiretroviral therapy adjuvant therapy 

The Trojan Horse model proposes that infected monocytes (but also macrophages and CD4 T cells) cross the blood-brain barrier in response to chemokine stimulation. After infiltrating brain parenchyma, these cells also release additional chemokines and further attract additional inflammatory cells (Strelow et al., 2001). 

Alternatively, endothelial cells and astrocytes (which compose the blood-brain barrier) are infected directly (Strelow et al., 2001). A variant of this theory is that infectious virions are transported in the cytoplasm of astrocytes and endothelial cells, and eventually transferred to central nervous system cells by trans-cytosis or macropynocytosis) (Marechal et al., 2001). 

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Sevigny JJ, Albert SM, McDermott MP, McArthur JC, Sacktor N, Conant K, Schifitto G, Seines OA, Stem Y, McClernon DR, Palumbo D, Kieburtz K, Riggs G, Cohen B, Epstein LG, Marder K (2004) Evaluation of HIV RNA and markers of immune activation as predictors of HIV-associated dementia. Neurology 63(ll) 2084-2090... 

Woods SP, Conover E, Rippeth ID, Carey CL, Gonzalez R, Marcotte TD, Heaton RK, Grant I (2004) Qualitative aspects of verbal fluency in HIV-associated dementia a deficit in rule-guided lexical-semantic search processes Neuropsychologia 42(6) 801-809... 

Alzheimer s disease in which the pathogenicity of amyloid peptides depends on proteases, namely secretases, involved in amyloid precursor protein (APP) maturation. This chapter will describe how the proteolysis of chemokines might participate in the neuropathogenesis of HIV infection, thus contributing to the development of the central nervous system disorder termed HIV-associated dementia (HAD). 

Kaul M, Garden GA, Lipton SA (2001) Pathways to neuronal injury and apoptosis in HIV-associated dementia. Nature 410 988-994... 

Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R, Kitazawa S, Miyachi H, Maeda S, Egashira K, Kasuga M (2006) MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Qin Invest 116 1494-1505 Kaul M, Garden GA, Lipton SA (2001) Pathways to neuronal injury and apoptosis in HIV-associated dementia. Nature 410 988-994... 

Opiate drug exposure has a significant impact on HIV infection as well as progression to HIV-associated dementia. On a cellular level it is comprehendible that drugs of abuse such as opioids would reduce the threshold for neurotoxicity such that a marginally toxic insult would now be exacerbated and lead to cell death or injury... 

Besides AD, memantine has been used for the treatment of stroke, Parkinson disease, amyotrophic lateral sclerosis, epilepsy, HIV associated dementia,... 

III. Calcium-Dependent Glutamate Release from Astrocytes is Deregulated in Pathological Conditions with an Inflammatory Component A. The Case of HIV-Associated Dementia... 

Glass ID, Wesselingh SL, Seines OA, McArfiiur- JC (1993) Clinical neuT opatliologic coiTelation in HIV-associated dementia. Neurology 43 223(V2237. 

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