HIV-1 associated dementia: Symptoms and causes

Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Pennsylvania 19122, USA.
Retrovirology (Impact Factor: 4.19). 02/2006; 3(1):28. DOI: 10.1186/1742-4690-3-28
Source: PubMed


Despite the use of highly active antiretroviral therapy (HAART), neuronal cell death remains a problem that is frequently found in the brains of HIV-1-infected patients. HAART has successfully prevented many of the former end-stage complications of AIDS, however, with increased survival times, the prevalence of minor HIV-1 associated cognitive impairment appears to be rising among AIDS patients. Further, HIV-1 associated dementia (HAD) is still prevalent in treated patients as well as attenuated forms of HAD and CNS opportunistic disorders. HIV-associated cognitive impairment correlates with the increased presence in the CNS of activated, though not necessarily HIV-1-infected, microglia and CNS macrophages. This suggests that indirect mechanisms of neuronal injury and loss/death occur in HIV/AIDS as a basis for dementia since neurons are not themselves productively infected by HIV-1. In this review, we discussed the symptoms and causes leading to HAD. Outcome from this review will provide new information regarding mechanisms of neuronal loss in AIDS patients.

Download full-text


Available from: Shohreh Amini
  • Source
    • "u - rons ( Fig . 2 ) . Within 4 h , labeled monocyte - derived exosomes were internalized by neural cells , as observed by confocal microscopy . That monocyte - derived exosomes are inter - nalized by neural cells may have implications in several neurological disorders characterized by peripheral inflam - mation such as HIV - associated dementia ( Ghafouri et al . , 2006 ) ."
    [Show abstract] [Hide abstract]
    ABSTRACT: Extracellular vesicles classified as exosomes, microvesicles, or apoptotic bodies based on size are shed from most cells under normal as well as pathological conditions. They are released into the surrounding milieu, including plasma, urine, saliva, and tissues. Exosomes are highly enriched in microRNAs (miRs), which function in recipient cells by regulating posttranscriptional processing of targeted genes. Interaction of a miR with its mRNA target typically results in suppression of its gene expression. Peripheral inflammatory conditions can modulate miR expression in immune cells such as circulating monocytes that can influence their migration and differentiation. Changes within monocyte-derived macrophage miR expression can influence exosome content and further affect end-organ target cells.
    Full-text · Article · May 2015 · DNA and cell biology
  • Source
    • "The introduction of antiretroviral therapy (ART) has reduced the prevalence of dementia. However, as the lifespan of HIV-1 infected patients has been prolonged by ART, the prevalence of HAND with aging remains high [4]. HAND probably arises from direct and maintained viral invasion of the central nervous system (CNS), which is an important reservoir for HIV-1 virus regardless of plasma viral suppression or cumulative time on ART. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Older human immunodeficiency virus (HIV)-1 transgenic rats are a model for HIV-1 associated neurocognitive disorders (HAND). They show behavioral changes, neuroinflammation, neuronal loss, and increased brain arachidonic acid (AA) enzymes. Aspirin (acetylsalicylate, ASA) inhibits AA oxidation by cyclooxygenase (COX)-1 and COX-2. Chronic low-dose ASA will downregulate brain AA metabolism in HIV-1 transgenic rats. Nine month-old HIV-1 transgenic and wildtype rats were given 42 days of 10mg/kg/day ASA or nothing in drinking water; eicosanoids were measured using ELISAs on microwaved brain extracts. Brain 15-epi-lipoxin A4 and 8-isoprostane concentrations were significantly higher in HIV-1 transgenic than wildtype rats; these differences were prevented by ASA. ASA reduced prostaglandin E2 and leukotriene B4 concentrations in HIV-1 Tg but not wildtype rats. Thromboxane B2, 15-HETE, lipoxin A4 and resolvin D1 concentrations were unaffected by genotype or treatment. Chronic low-dose ASA reduces AA-metabolite markers of neuroinflammation and oxidative stress in a rat model for HAND. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Jan 2015 · Prostaglandins Leukotrienes and Essential Fatty Acids
  • Source
    • "The " Trojan Horse Hypothesis " model states that, in HIV + subjects, the loss of blood–brain barrier (BBB) integrity allows infected cells to enter the CNS. HIV released from the infected cells causes infection in brain tissues resulting in inflammation, neuronal damage and the establishment of central reservoirs (Ghafouri et al. 2006; Kaul 2009; Lamers et al. 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: HIV-1 infection can lead to neurocognitive impairment collectively known as HIV-associated neurocognitive disorders (HAND). Although combined antiretroviral treatment (cART) has significantly ameliorated HIV's morbidity and mortality, persistent neuroinflammation and neurocognitive dysfunction continue. This review focuses on the current clinical and molecular evidence of the viral and host factors that influence glutamate-mediated neurotoxicity and neuropathogenesis as an important underlying mechanism during the course of HAND development. In addition, discusses potential pharmacological strategies targeting the glutamatergic system that may help prevent and improve neurological outcomes in HIV-1-infected subjects.
    Full-text · Article · May 2014 · Journal of NeuroVirology
Show more