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Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1998 Jul;65(1):23–28. doi: 10.1136/jnnp.65.1.23

Hypothesis on the pathogenesis of vacuolar myelopathy, dementia, and peripheral neuropathy in AIDS

S Tan 1, R Guiloff 1
PMCID: PMC2170156  PMID: 9667556

Abstract

Certain aspects of the clinical syndrome of dementia, cerebral atrophy, predominantly sensory neuropathy, and vacuolar myelopathy in AIDS resemble those seen in vitamin B12 deficiency. Pathologically, there are similarities not only in the changes in the spinal cord, but also in the brain and peripheral nerves. The pathogenesis of vacuolar myelopathy may be secondary to a combination of immune mediated myelin and oligodendrocyte injury, and simultaneous impairment of repair mechanisms due to a deficiency of S-adenosylmethionine (SAM). Products derived from macrophages may interfere directly with the methyl transfer cycle through the generation of reactive oxygen intermediates and reactions involving nitric oxide and peroxynitrite which may limit the supply of methionine for conversion to SAM, both by direct interaction as well as through inhibition of methionine synthase. Macrophage activation with secretion of cytokines and other biologically reactive substances within the nervous system is sustained in the late stages of HIV infection by the general effects of immune depletion, including loss of T cells (with concomitant reduction of macrophage regulatory molecules) and recurrent opportunistic infections, and may be further augmented by the local presence of the virus itself (or its surface glycoprotein gp120). This would account for the common, but not exclusive, occurrence of vacuolar myelopathy in AIDS. The ability of the virus and its products to stimulate macrophage and microglial activation may also explain the association between severity ofvacuolar myelopathy and the presence of HIV encephalitis. A similar mechanism may underlie the pathogenesis of dementia, cerebral atrophy, and peripheral neuropathy. Local factors or differential susceptibility between the central and peripheral nervous system may determine whether myelinotoxic or neurotoxic processes predominate; the prominence of myelin involvement in the spinal cord, and axonal involvement peripherally may reflect both ends of this range, with the brain manifesting a more equal balance of both processes. 



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Selected References

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  1. Akaike A., Tamura Y., Sato Y., Yokota T. Protective effects of a vitamin B12 analog, methylcobalamin, against glutamate cytotoxicity in cultured cortical neurons. Eur J Pharmacol. 1993 Sep 7;241(1):1–6. doi: 10.1016/0014-2999(93)90925-8. [DOI] [PubMed] [Google Scholar]
  2. Apostolski S., McAlarney T., Quattrini A., Levison S. W., Rosoklija G., Lugaressi A., Corbo M., Sadiq S. A., Lederman S., Hays A. P. The gp120 glycoprotein of human immunodeficiency virus type 1 binds to sensory ganglion neurons. Ann Neurol. 1993 Dec;34(6):855–863. doi: 10.1002/ana.410340616. [DOI] [PubMed] [Google Scholar]
  3. Baldessarini R. J. Neuropharmacology of S-adenosyl-L-methionine. Am J Med. 1987 Nov 20;83(5A):95–103. doi: 10.1016/0002-9343(87)90860-6. [DOI] [PubMed] [Google Scholar]
  4. Benveniste E. N. Cytokine circuits in brain. Implications for AIDS dementia complex. Res Publ Assoc Res Nerv Ment Dis. 1994;72:71–88. [PubMed] [Google Scholar]
  5. Berger R., Nowak H. A new medical approach to the treatment of osteoarthritis. Report of an open phase IV study with ademetionine (Gumbaral). Am J Med. 1987 Nov 20;83(5A):84–88. doi: 10.1016/0002-9343(87)90858-8. [DOI] [PubMed] [Google Scholar]
  6. Bottiglieri T., Hyland K., Reynolds E. H. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs. 1994 Aug;48(2):137–152. doi: 10.2165/00003495-199448020-00002. [DOI] [PubMed] [Google Scholar]
  7. Bottiglieri T., Laundy M., Martin R., Carney M. W., Nissenbaum H., Toone B. K., Johnson A. L., Reynolds E. H. S-adenosylmethionine influences monoamine metabolism. Lancet. 1984 Jul 28;2(8396):224–224. doi: 10.1016/s0140-6736(84)90507-5. [DOI] [PubMed] [Google Scholar]
  8. Bukrinsky M. I., Nottet H. S., Schmidtmayerova H., Dubrovsky L., Flanagan C. R., Mullins M. E., Lipton S. A., Gendelman H. E. Regulation of nitric oxide synthase activity in human immunodeficiency virus type 1 (HIV-1)-infected monocytes: implications for HIV-associated neurological disease. J Exp Med. 1995 Feb 1;181(2):735–745. doi: 10.1084/jem.181.2.735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Castagna A., Le Grazie C., Accordini A., Giulidori P., Cavalli G., Bottiglieri T., Lazzarin A. Cerebrospinal fluid S-adenosylmethionine (SAMe) and glutathione concentrations in HIV infection: effect of parenteral treatment with SAMe. Neurology. 1995 Sep;45(9):1678–1683. doi: 10.1212/wnl.45.9.1678. [DOI] [PubMed] [Google Scholar]
  10. Chamouard J. M., Smadja D., Chaunu M. P., Bouche P. Neuropathie par vasculite nécrosante au cours de l'infection par le VIH1. Rev Neurol (Paris) 1993;149(5):358–361. [PubMed] [Google Scholar]
  11. Chiodi F., Norkrans G., Hagberg L., Sönnerborg A., Gaines H., Frøland S., Fenyö E. M., Norrby E., Vandvik B. Human immunodeficiency virus infection of the brain. II. Detection of intrathecally synthesized antibodies by enzyme linked immunosorbent assay and imprint immunofixation. J Neurol Sci. 1988 Oct;87(1):37–48. doi: 10.1016/0022-510x(88)90052-4. [DOI] [PubMed] [Google Scholar]
  12. Dawson V. L., Dawson T. M., Uhl G. R., Snyder S. H. Human immunodeficiency virus type 1 coat protein neurotoxicity mediated by nitric oxide in primary cortical cultures. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3256–3259. doi: 10.1073/pnas.90.8.3256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dinn J. J., McCann S., Wilson P., Reed B., Weir D., Scott J. Animal model for subacute combined degeneration. Lancet. 1978 Nov 25;2(8100):1154–1154. doi: 10.1016/s0140-6736(78)92314-0. [DOI] [PubMed] [Google Scholar]
  14. Everall I. P., Luthert P. J., Lantos P. L. Neuronal loss in the frontal cortex in HIV infection. Lancet. 1991 May 11;337(8750):1119–1121. doi: 10.1016/0140-6736(91)92786-2. [DOI] [PubMed] [Google Scholar]
  15. Fuller G. N., Jacobs J. M., Guiloff R. J. Association of painful peripheral neuropathy in AIDS with cytomegalovirus infection. Lancet. 1989 Oct 21;2(8669):937–941. doi: 10.1016/s0140-6736(89)90952-5. [DOI] [PubMed] [Google Scholar]
  16. Fuller G. N., Jacobs J. M., Guiloff R. J. Axonal atrophy in the painful peripheral neuropathy in AIDS. Acta Neuropathol. 1990;81(2):198–203. doi: 10.1007/BF00334508. [DOI] [PubMed] [Google Scholar]
  17. Fuller G. N., Jacobs J. M., Guiloff R. J. Nature and incidence of peripheral nerve syndromes in HIV infection. J Neurol Neurosurg Psychiatry. 1993 Apr;56(4):372–381. doi: 10.1136/jnnp.56.4.372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gelman B. B., Guinto F. C., Jr Morphometry, histopathology, and tomography of cerebral atrophy in the acquired immunodeficiency syndrome. Ann Neurol. 1992 Jul;32(1):31–40. doi: 10.1002/ana.410320107. [DOI] [PubMed] [Google Scholar]
  19. Genis P., Jett M., Bernton E. W., Boyle T., Gelbard H. A., Dzenko K., Keane R. W., Resnick L., Mizrachi Y., Volsky D. J. Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease. J Exp Med. 1992 Dec 1;176(6):1703–1718. doi: 10.1084/jem.176.6.1703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Glass J. D., Wesselingh S. L., Selnes O. A., McArthur J. C. Clinical-neuropathologic correlation in HIV-associated dementia. Neurology. 1993 Nov;43(11):2230–2237. doi: 10.1212/wnl.43.11.2230. [DOI] [PubMed] [Google Scholar]
  21. Goudreau G., Carpenter S., Beaulieu N., Jolicoeur P. Vacuolar myelopathy in transgenic mice expressing human immunodeficiency virus type 1 proteins under the regulation of the myelin basic protein gene promoter. Nat Med. 1996 Jun;2(6):655–661. doi: 10.1038/nm0696-655. [DOI] [PubMed] [Google Scholar]
  22. Harriman G. R., Smith P. D., Horne M. K., Fox C. H., Koenig S., Lack E. E., Lane H. C., Fauci A. S. Vitamin B12 malabsorption in patients with acquired immunodeficiency syndrome. Arch Intern Med. 1989 Sep;149(9):2039–2041. [PubMed] [Google Scholar]
  23. Healton E. B., Savage D. G., Brust J. C., Garrett T. J., Lindenbaum J. Neurologic aspects of cobalamin deficiency. Medicine (Baltimore) 1991 Jul;70(4):229–245. doi: 10.1097/00005792-199107000-00001. [DOI] [PubMed] [Google Scholar]
  24. Heyes M. P., Brew B. J., Martin A., Price R. W., Salazar A. M., Sidtis J. J., Yergey J. A., Mouradian M. M., Sadler A. E., Keilp J. Quinolinic acid in cerebrospinal fluid and serum in HIV-1 infection: relationship to clinical and neurological status. Ann Neurol. 1991 Feb;29(2):202–209. doi: 10.1002/ana.410290215. [DOI] [PubMed] [Google Scholar]
  25. Hirata F., Axelrod J. Phospholipid methylation and biological signal transmission. Science. 1980 Sep 5;209(4461):1082–1090. doi: 10.1126/science.6157192. [DOI] [PubMed] [Google Scholar]
  26. Kamin S. S., Petito C. K. Idiopathic myelopathies with white matter vacuolation in non-acquired immunodeficiency syndrome patients. Hum Pathol. 1991 Aug;22(8):816–824. doi: 10.1016/0046-8177(91)90211-7. [DOI] [PubMed] [Google Scholar]
  27. Keating J. N., Trimble K. C., Mulcahy F., Scott J. M., Weir D. G. Evidence of brain methyltransferase inhibition and early brain involvement in HIV-positive patients. Lancet. 1991 Apr 20;337(8747):935–939. doi: 10.1016/0140-6736(91)91570-k. [DOI] [PubMed] [Google Scholar]
  28. Layzer R. B. Myeloneuropathy after prolonged exposure to nitrous oxide. Lancet. 1978 Dec 9;2(8102):1227–1230. doi: 10.1016/s0140-6736(78)92101-3. [DOI] [PubMed] [Google Scholar]
  29. Lipkin W. I., Parry G., Kiprov D., Abrams D. Inflammatory neuropathy in homosexual men with lymphadenopathy. Neurology. 1985 Oct;35(10):1479–1483. doi: 10.1212/wnl.35.10.1479. [DOI] [PubMed] [Google Scholar]
  30. Mastroianni C. M., Sebastiani G., Folgori F., Ajassa C., Vullo V., Volpi A. Detection of cytomegalovirus-matrix protein (pp65) in leukocytes of HIV-infected patients with painful peripheral neuropathy. J Med Virol. 1994 Oct;44(2):172–175. doi: 10.1002/jmv.1890440210. [DOI] [PubMed] [Google Scholar]
  31. McCall T., Vallance P. Nitric oxide takes centre-stage with newly defined roles. Trends Pharmacol Sci. 1992 Jan;13(1):1–6. doi: 10.1016/0165-6147(92)90002-n. [DOI] [PubMed] [Google Scholar]
  32. Miller B., Sarantis M., Traynelis S. F., Attwell D. Potentiation of NMDA receptor currents by arachidonic acid. Nature. 1992 Feb 20;355(6362):722–725. doi: 10.1038/355722a0. [DOI] [PubMed] [Google Scholar]
  33. Nicolaou A., Ast T., Garcia C. V., Anderson M. M., Gibbons J. M., Gibbons W. A. In vitro NO and N2O inhibition of the branch point enzyme vitamin B12 dependent methionine synthase from rat brain synaptosomes. Biochem Soc Trans. 1994 Aug;22(3):296S–296S. doi: 10.1042/bst022296s. [DOI] [PubMed] [Google Scholar]
  34. Olanow C. W. A radical hypothesis for neurodegeneration. Trends Neurosci. 1993 Nov;16(11):439–444. doi: 10.1016/0166-2236(93)90070-3. [DOI] [PubMed] [Google Scholar]
  35. Pajares M. A., Durán C., Corrales F., Pliego M. M., Mato J. M. Modulation of rat liver S-adenosylmethionine synthetase activity by glutathione. J Biol Chem. 1992 Sep 5;267(25):17598–17605. [PubMed] [Google Scholar]
  36. Petito C. K., Navia B. A., Cho E. S., Jordan B. D., George D. C., Price R. W. Vacuolar myelopathy pathologically resembling subacute combined degeneration in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1985 Apr 4;312(14):874–879. doi: 10.1056/NEJM198504043121402. [DOI] [PubMed] [Google Scholar]
  37. Petito C. K., Vecchio D., Chen Y. T. HIV antigen and DNA in AIDS spinal cords correlate with macrophage infiltration but not with vacuolar myelopathy. J Neuropathol Exp Neurol. 1994 Jan;53(1):86–94. doi: 10.1097/00005072-199401000-00011. [DOI] [PubMed] [Google Scholar]
  38. Poli G., Kinter A., Justement J. S., Kehrl J. H., Bressler P., Stanley S., Fauci A. S. Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression. Proc Natl Acad Sci U S A. 1990 Jan;87(2):782–785. doi: 10.1073/pnas.87.2.782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Pryor W. A., Jin X., Squadrito G. L. One- and two-electron oxidations of methionine by peroxynitrite. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11173–11177. doi: 10.1073/pnas.91.23.11173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Radi R., Beckman J. S., Bush K. M., Freeman B. A. Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide. J Biol Chem. 1991 Mar 5;266(7):4244–4250. [PubMed] [Google Scholar]
  41. Radi R., Beckman J. S., Bush K. M., Freeman B. A. Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys. 1991 Aug 1;288(2):481–487. doi: 10.1016/0003-9861(91)90224-7. [DOI] [PubMed] [Google Scholar]
  42. Rosenberg Z. F., Fauci A. S. Immunopathogenesis of HIV infection. FASEB J. 1991 Jul;5(10):2382–2390. doi: 10.1096/fasebj.5.10.1676689. [DOI] [PubMed] [Google Scholar]
  43. Rosenberg Z. F., Fauci A. S. Immunopathogenic mechanisms of HIV infection: cytokine induction of HIV expression. Immunol Today. 1990 May;11(5):176–180. doi: 10.1016/0167-5699(90)90070-p. [DOI] [PubMed] [Google Scholar]
  44. Rosenblum M., Scheck A. C., Cronin K., Brew B. J., Khan A., Paul M., Price R. W. Dissociation of AIDS-related vacuolar myelopathy and productive HIV-1 infection of the spinal cord. Neurology. 1989 Jul;39(7):892–896. doi: 10.1212/wnl.39.7.892. [DOI] [PubMed] [Google Scholar]
  45. Schmidbauer M., Huemer M., Cristina S., Trabattoni G. R., Budka H. Morphological spectrum, distribution and clinical correlation of white matter lesions in AIDS brains. Neuropathol Appl Neurobiol. 1992 Oct;18(5):489–501. doi: 10.1111/j.1365-2990.1992.tb00816.x. [DOI] [PubMed] [Google Scholar]
  46. Scott J. M., Dinn J., Wilson P., Weir D. G. Subacute combined degeneration. Lancet. 1982 Jan 2;1(8262):51–52. doi: 10.1016/s0140-6736(82)92599-5. [DOI] [PubMed] [Google Scholar]
  47. Scott J. M., Weir D. G. The methyl folate trap. A physiological response in man to prevent methyl group deficiency in kwashiorkor (methionine deficiency) and an explanation for folic-acid induced exacerbation of subacute combined degeneration in pernicious anaemia. Lancet. 1981 Aug 15;2(8242):337–340. doi: 10.1016/s0140-6736(81)90650-4. [DOI] [PubMed] [Google Scholar]
  48. Selmaj K. W., Raine C. S. Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol. 1988 Apr;23(4):339–346. doi: 10.1002/ana.410230405. [DOI] [PubMed] [Google Scholar]
  49. Selmaj K., Raine C. S., Farooq M., Norton W. T., Brosnan C. F. Cytokine cytotoxicity against oligodendrocytes. Apoptosis induced by lymphotoxin. J Immunol. 1991 Sep 1;147(5):1522–1529. [PubMed] [Google Scholar]
  50. Sherry B., Cerami A. Cachectin/tumor necrosis factor exerts endocrine, paracrine, and autocrine control of inflammatory responses. J Cell Biol. 1988 Oct;107(4):1269–1277. doi: 10.1083/jcb.107.4.1269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Simpson D. M., Tagliati M. Nucleoside analogue-associated peripheral neuropathy in human immunodeficiency virus infection. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Jun 1;9(2):153–161. [PubMed] [Google Scholar]
  52. Snyder S. H. Nitric oxide and neurons. Curr Opin Neurobiol. 1992 Jun;2(3):323–327. doi: 10.1016/0959-4388(92)90123-3. [DOI] [PubMed] [Google Scholar]
  53. Stramentinoli G. Pharmacologic aspects of S-adenosylmethionine. Pharmacokinetics and pharmacodynamics. Am J Med. 1987 Nov 20;83(5A):35–42. doi: 10.1016/0002-9343(87)90849-7. [DOI] [PubMed] [Google Scholar]
  54. Stuehr D. J., Cho H. J., Kwon N. S., Weise M. F., Nathan C. F. Purification and characterization of the cytokine-induced macrophage nitric oxide synthase: an FAD- and FMN-containing flavoprotein. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7773–7777. doi: 10.1073/pnas.88.17.7773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Surtees R. Biochemical pathogenesis of subacute combined degeneration of the spinal cord and brain. J Inherit Metab Dis. 1993;16(4):762–770. doi: 10.1007/BF00711908. [DOI] [PubMed] [Google Scholar]
  56. Surtees R., Hyland K., Smith I. Central-nervous-system methyl-group metabolism in children with neurological complications of HIV infection. Lancet. 1990 Mar 17;335(8690):619–621. doi: 10.1016/0140-6736(90)90409-x. [DOI] [PubMed] [Google Scholar]
  57. Surtees R., Leonard J., Austin S. Association of demyelination with deficiency of cerebrospinal-fluid S-adenosylmethionine in inborn errors of methyl-transfer pathway. Lancet. 1991 Dec 21;338(8782-8783):1550–1554. doi: 10.1016/0140-6736(91)92373-a. [DOI] [PubMed] [Google Scholar]
  58. Tan S. V., Guiloff R. J., Henderson D. C., Gazzard B. G., Miller R. AIDS-associated vacuolar myelopathy and tumor necrosis factor-alpha (TNF alpha). J Neurol Sci. 1996 Jun;138(1-2):134–144. doi: 10.1016/0022-510x(95)00354-5. [DOI] [PubMed] [Google Scholar]
  59. Tan S. V., Guiloff R. J., Scaravilli F. AIDS-associated vacuolar myelopathy. A morphometric study. Brain. 1995 Oct;118(Pt 5):1247–1261. doi: 10.1093/brain/118.5.1247. [DOI] [PubMed] [Google Scholar]
  60. Tweardy D. J., Glazer E. W., Mott P. L., Anderson K. Modulation by tumor necrosis factor-alpha of human astroglial cell production of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF). J Neuroimmunol. 1991 Jun;32(3):269–278. doi: 10.1016/0165-5728(91)90197-f. [DOI] [PubMed] [Google Scholar]
  61. Tyor W. R., Glass J. D., Baumrind N., McArthur J. C., Griffin J. W., Becker P. S., Griffin D. E. Cytokine expression of macrophages in HIV-1-associated vacuolar myelopathy. Neurology. 1993 May;43(5):1002–1009. doi: 10.1212/wnl.43.5.1002. [DOI] [PubMed] [Google Scholar]
  62. Tyor W. R., Glass J. D., Griffin J. W., Becker P. S., McArthur J. C., Bezman L., Griffin D. E. Cytokine expression in the brain during the acquired immunodeficiency syndrome. Ann Neurol. 1992 Apr;31(4):349–360. doi: 10.1002/ana.410310402. [DOI] [PubMed] [Google Scholar]
  63. Tyor W. R., Wesselingh S. L., Griffin J. W., McArthur J. C., Griffin D. E. Unifying hypothesis for the pathogenesis of HIV-associated dementia complex, vacuolar myelopathy, and sensory neuropathy. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Aug 1;9(4):379–388. [PubMed] [Google Scholar]
  64. VICTOR M., LEAR A. A. Subacute combined degeneration of the spinal cord; current concepts of the disease process; value of serum vitamin B12; determinations in clarifying some of the common clinical problems. Am J Med. 1956 Jun;20(6):896–911. doi: 10.1016/0002-9343(56)90210-8. [DOI] [PubMed] [Google Scholar]
  65. Vara E., Arias-Díaz J., García C., Villa N., Simón C., Ortiz P., Balibrea J. L. S-adenosyl-methionine may protect transplanted hepatocytes against the toxic effects of cytokines. Transplant Proc. 1994 Dec;26(6):3364–3366. [PubMed] [Google Scholar]
  66. Veilleux M., Paltiel O., Falutz J. Sensorimotor neuropathy and abnormal vitamin B12 metabolism in early HIV infection. Can J Neurol Sci. 1995 Feb;22(1):43–46. doi: 10.1017/s0317167100040488. [DOI] [PubMed] [Google Scholar]
  67. Wahl L. M., Corcoran M. L., Pyle S. W., Arthur L. O., Harel-Bellan A., Farrar W. L. Human immunodeficiency virus glycoprotein (gp120) induction of monocyte arachidonic acid metabolites and interleukin 1. Proc Natl Acad Sci U S A. 1989 Jan;86(2):621–625. doi: 10.1073/pnas.86.2.621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Weiser B., Peress N., La Neve D., Eilbott D. J., Seidman R., Burger H. Human immunodeficiency virus type 1 expression in the central nervous system correlates directly with extent of disease. Proc Natl Acad Sci U S A. 1990 May;87(10):3997–4001. doi: 10.1073/pnas.87.10.3997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Wesselingh S. L., Glass J., McArthur J. C., Griffin J. W., Griffin D. E. Cytokine dysregulation in HIV-associated neurological disease. Adv Neuroimmunol. 1994;4(3):199–206. doi: 10.1016/s0960-5428(06)80258-5. [DOI] [PubMed] [Google Scholar]
  70. Wesselingh S. L., Power C., Glass J. D., Tyor W. R., McArthur J. C., Farber J. M., Griffin J. W., Griffin D. E. Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dementia. Ann Neurol. 1993 Jun;33(6):576–582. doi: 10.1002/ana.410330604. [DOI] [PubMed] [Google Scholar]
  71. Zhao X. J., Sampath V., Caughey W. S. Cytochrome c oxidase catalysis of the reduction of nitric oxide to nitrous oxide. Biochem Biophys Res Commun. 1995 Jul 26;212(3):1054–1060. doi: 10.1006/bbrc.1995.2076. [DOI] [PubMed] [Google Scholar]
  72. van den Berg L. H., Sadiq S. A., Lederman S., Latov N. The gp120 glycoprotein of HIV-1 binds to sulfatide and to the myelin associated glycoprotein. J Neurosci Res. 1992 Dec;33(4):513–518. doi: 10.1002/jnr.490330403. [DOI] [PubMed] [Google Scholar]

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