Document 0268
 DOCN  M9550268
 TI    AIDS-related dementia and calcium homeostasis.
 DT    9505
 AU    Lipton SA; Department of Neurology, Children's Hospital, Boston,;
       Massachusetts.
 SO    Ann N Y Acad Sci. 1994 Dec 15;747:205-24. Unique Identifier : AIDSLINE
       MED/95150339
 AB    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.
 DE    Astrocytes/PHYSIOLOGY  AIDS Dementia Complex/DRUG
       THERAPY/PATHOLOGY/*PHYSIOPATHOLOGY  Calcium/*PHYSIOLOGY  Calcium Channel
       Blockers/PHARMACOLOGY  Central Nervous System/PATHOLOGY  Homeostasis
       Human  HIV Envelope Protein gp120/PHARMACOLOGY  Monocytes/PHYSIOLOGY
       Nerve Degeneration  Oligodendroglia/PHYSIOLOGY  Receptors,
       N-Methyl-D-Aspartate/ANTAGONISTS & INHIB/PHYSIOLOGY  Support, Non-U.S.
       Gov't  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE  REVIEW  REVIEW,
       ACADEMIC

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).