- AIDS related dementia, nice overview

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Ann N Y Acad Sci. 1994 Dec 15;747:205-24.

AIDS-related dementia and calcium homeostasis.

Lipton SA.Department of Neurology, Children's Hospital, Boston, Massachusetts.

Approximately a third of adults and half of

children with acquired immunodeficiency syndrome (AIDS) eventually

suffer from neurological manifestations, including dysfunction of

cognition, movement, and sensation. Among the various pathologies

reported in the brain of patients with AIDS is neuronal injury and

loss. A paradox arises, however, because neurons themselves are for all

intents and purposes not infected by human immunodeficiency virus type

1 (HIV-1). This paper reviews evidence suggesting that at least part of

the neuronal injury observed in the brain of AIDS patients is related

to excessive influx of Ca2+. There is growing support for the existence

of HIV- or immune-related toxins that lead indirectly to the injury or

death of neurons via a potentially complex web of interactions between

macrophages (or microglia), astrocytes, and neurons. Human

immunodeficiency virus-infected monocytoid cells (macrophages,

microglia, or monocytes), especially after interacting with astrocytes,

secrete substances that potentially contribute to neurotoxicity. Not

all of these substances are yet known, but they may include

eicosanoids, that is, arachidonic acid and its metabolites, as well as

platelet-activating factor. Macrophages activated by HIV-1 envelope

protein gp120 also appear to release arachidonic acid and its

metabolites. These factors can lead to increased glutamate release or

decreased glutamate reuptake. In addition, gamma interferon (IFN-gamma)

stimulation of macrophages induce release of the glutamate-like agonist

quinolinate. Human immunodeficiency virus-infected or gp120-stimulated

macrophages also produce cytokines, including tumor necrosis

factor-alpha and interleukin-1 beta, which contribute to astrogliosis.

A final common pathway for neuronal susceptibility appears to be

operative, similar to that observed in stroke, trauma, epilepsy,

neuropathic pain, and several neurodegenerative diseases, possibly

including Huntington's disease, Parkinson's disease, and amyotrophic

lateral sclerosis. This mechanism involves the activation of

voltage-dependent Ca2+ channels and N-methyl-D-aspartate (NMDA)

receptor-operated channels, and therefore offers hope for future

pharmacological intervention. This review focuses on clinically

tolerated calcium channel antagonists and NMDA antagonists with the

potential for trials in humans with AIDS dementia in the near future.

PMID: 7847672 [PubMed - indexed for MEDLINE]