Neuronal loss in symptom-free HIV infection

Everall, Ian; Gray, Françoise; Barnes, H.; Durigon, Michel; Luthert, Philip J.

doi:10.1016/0140-6736(92)92603-d

Cited by 31 publications

(17 citation statements)

References 10 publications

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“…Apoptotic neuronal loss has been well documented in H IV E cases and was detected mainly in the neocortex, limbic system and basal ganglia [36]. Rare apoptotic neurones have been seen in some late HIV asymptomatic cases [37], but generally neuronal loss is not thought to occur till the symptomatic phase of HIV infection [12,30,38]. These findings are in accordance with an increased viral load seen in the brain at this stage of disease.…”

Section: Neuronal Damage In Aidssupporting

confidence: 74%

“…There is accumulative evidence that neurological A ID S can be correlated with an increased viral load, vary ing forms of neuronal damage and increased levels of potential neurotoxins in the C SF [reviewed in 10 and 28], Moreover, numerous studies have shown that at the cellu lar level in A ID S there is a 38-50% neuronal loss through out regions of the cerebral cortex [29][30][31] and a 30-50% decrease in large, pyramidal neurones with simplification of neuronal processes [32,33].…”

Section: Neuronal Damage In Aidsmentioning

confidence: 99%

“…In H IVE, different neuronal populations seem to be selectively vulnerable to damage by apoptotic pro cesses [reviewed in 28]. These include large pyramidal neurones and interneurones in the cortex [29][30][31][32]. spiny neurones in the putamen [39], and CA3 interneuroncs of the hippocampus [31].…”

Section: Neuronal Damage In Aidsmentioning

confidence: 99%

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Neuronal Damage and Its Relation to Dementia in Acquired Immunodeficiency Syndrome (AIDS)

Trillo-Pazos¹,

Everall²

1996

Pathobiology

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There are an estimated 21.8 million people infected with human immunodeficiency virus (HIV) worldwide [Weekly Epidemiol Rec 1996;27:204-208] and 90% of these people will have some form of neuropathological abnormality during the course of acquired immunodeficiency syndrome (AIDS). In this review, we will highlight the primary HIV-associated brain disorders. The role of HIV proteins and cytokines on neuronal damage will be assessed. We will also discuss the role of neuronal loss and functional damage in HIV-associated dementia.

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Section: Neuronal Damage In Aidssupporting

confidence: 74%

Section: Neuronal Damage In Aidsmentioning

confidence: 99%

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Neuronal Damage and Its Relation to Dementia in Acquired Immunodeficiency Syndrome (AIDS)

Trillo-Pazos¹,

Everall²

1996

Pathobiology

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“…Microglial activation was proposed as a better correlate for cognitive impairment than viral multiplication in full-blown AIDS (48), but no clear correlation between microglial activation, neuronal damage, and cognitive disorders could be found at that stage (6). This discrepancy is particularly striking in pre-AIDS cases that show conspicuous microglial activation (49,50) but have no obvious cognitive disorder, no neuronal loss (51), and little or no neuronal apoptosis (6,7,49,52).…”

Section: Discussionmentioning

confidence: 75%

Expression of Excitatory Amino Acid Transporter-1 in Brain Macrophages and Microglia of HIV-Infected Patients. A Neuroprotective Role for Activated Microglia?

Vallat-Decouvelaere

Chrétien

Gras

et al. 2003

J Neuropathol Exp Neurol

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Abstract. Recent experimental studies showed that activated macrophages/microglia (AMM) express excitatory amino acid transporters (EAATs), suggesting that, in addition to their neurotoxic properties, they also have a neuroprotective role by clearing extracellular glutamate and producing antioxidant glutathione. To test this hypothesis in human, the brain of 12 HIVpositive patients and 3 controls were immunostained for EAAT-1. EAAT-1 was expressed by AMM in all HIV-infected cases but not in HIV-negative controls. Expression varied according to the disease stage. In 5 cases with active HIV-encephalitis (HIVE), AMM strongly expressed EAAT-1 in the white matter and basal ganglia, analogous to HLA-DR and CD68 expression. There was weaker expression in the cortex and perineuronal microglial cells were not involved. In a case with ''burnt out'' HIVE following highly active antiretroviral therapy (HAART), EAAT-1 expression was mild, identical to that of HLA-DR and CD68 in the white matter and cortex and involved perineuronal microglial cells. In 3 AIDS patients without HIVE and in 3 pre-AIDS cases, EAAT-1 expression in the white matter was weaker than HLA-DR and CD68 expression; there was stronger correlation in the gray matter where perineuronal microglial cells were stained predominantly. Our findings in humans tend to confirm that AMM, particularly perineuronal microglial cells, play a neuroprotective role in the early stages of HIV infection and, possibly, following treatment. This is in keeping with the early microglial activation seen in pre-AIDS cases, and the late occurrence of neuronal loss. It may also explain the reversible cognitive disorders following treatment in some cases.

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“…The importance of macrophages in HIV-associated neuropathogenesis is further underlined by the emergence of specific monocyte subsets in the peripheral blood of patients with HAD, which express specific markers and demonstrate enhanced ability to migrate and secrete neurotoxins (19,37,42). Nevertheless, a paradoxical contrast exists between macrophage/microglia activation, that may be set up early in the disease at the asymptomatic pre-AIDS stage (2,50), and the neuronal apoptosis (1) and loss (14) that occur very late (for review, see Ref. 15).…”

mentioning

confidence: 96%

Glutamate metabolism in HIV-infected macrophages: implications for the CNS

Porcheray

Léone²,

Samah³

et al. 2006

American Journal of Physiology-Cell Physiology

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Central nervous system disorders are still a common complication of human immunodeficiency virus (HIV) infection and can lead to dementia and death. They are mostly the consequences of an inflammatory macrophagic activation and relate to glutamate-mediated excitotoxicity. However, recent studies also suggest neuroprotective aspects of macrophage activation through the expression of glutamate transporters and glutamine synthetase. We thus aimed to study whether HIV infection or activation of macrophages could modulate glutamate metabolism in these cells. We assessed the effect of HIV infection on glutamate transporter expression as well as on glutamate uptake by macrophages and showed that glutamate transport was partially decreased in the course of virus replication, whereas excitatory amino acid transporter-2 (EAAT-2) gene expression was dramatically increased. The consequences of HIV infection on glutamine synthetase were also measured and for the first time we show the functional expression of this key enzyme in macrophages. This expression was repressed during virus production. We then quantified EAAT-1 and EAAT-2 gene expression as well as glutamate uptake in differentially activated macrophages and show that the effects of HIV are not directly related to pro- or anti-inflammatory mediators. Finally, this study shows that glutamate transport by macrophages is less affected than what has been described in astrocytes. Macrophages may thus play a role in neuroprotection against glutamate in the infected brain, through their expression of both EAATs and glutamine synthetase. Because glutamate metabolism by activated macrophages is sensitive to both HIV infection and inflammation, it may thus be of potential interest as a therapeutic target in HIV encephalitis.

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Neuronal loss in symptom-free HIV infection

Cited by 31 publications

References 10 publications

Neuronal Damage and Its Relation to Dementia in Acquired Immunodeficiency Syndrome (AIDS)

Neuronal Damage and Its Relation to Dementia in Acquired Immunodeficiency Syndrome (AIDS)

Expression of Excitatory Amino Acid Transporter-1 in Brain Macrophages and Microglia of HIV-Infected Patients. A Neuroprotective Role for Activated Microglia?

Glutamate metabolism in HIV-infected macrophages: implications for the CNS

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