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Inflammatory changes and breakdown of microvascular integrity in early human immunodeficiency virus dementia

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Abstract

Increased postcontrast enhancement in contrast-enhanced magnetic resonance imaging (CE-MRI) of the central nervous system (CNS) is a predictor of human immunodeficiency virus (HIV) dementia severity in HIV-infected subjects. The present study confirms this earlier finding in a mildly impaired patient cohort, and demonstrates that the increased postcontrast enhancement is correlated with increased cerebrospinal fluid (CSF) levels of monocyte chemoattractant protein (MCP)-1, an inflammatory chemokine, and increased CNS levels of mI, a microglial marker. These results suggest that early CNS inflammation may underlie the microvascular changes observed, and may be a factor in the development of HIV dementia.

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References

  • Alger JR, Symko SC, Bizzi A, Posse S, DesPres DJ, Armstrong MR (1993). Absolute quantitation of short TE brain 1H-MR spectra and spectroscopic imaging data. J Comput Assist Tomogr 17: 191–199.

    Article  CAS  PubMed  Google Scholar 

  • Andersson LM, Hagberg L, Fuchs D, Svennerholm B, Gisslen M (2001). Increased blood-brain barrier permeability in neuro-asymptomatic HIV-1-infected individuals—correlation with cerebrospinal fluid HIV-1 RNA and neopterin levels. J NeuroVirol 7: 542–547.

    Article  CAS  PubMed  Google Scholar 

  • Avison MJ, Nath A, Berger JR (2002). Understanding pathogenesis and treatment of HIV dementia: a role for magnetic resonance? Trends Neurosci 25: 468–473.

    Article  CAS  PubMed  Google Scholar 

  • Bagasra O, Lavi E, Bobroski L, Khalili K, Pestaner JP, Tawadros R, Pomerantz RJ (1996). Cellular reservoirs of HIV-1 in the central nervous system of infected individuals: identification by the combination of in situ polymerase chain reaction and immunohistochemistry. AIDS 10: 573–585.

    Article  CAS  PubMed  Google Scholar 

  • Barker PB, Lee RR, McArthur JC (1995). AIDS dementia complex: evaluation with proton MR spectroscopic imaging. Radiology 195: 58–64.

    CAS  PubMed  Google Scholar 

  • Bell JE (1998). The neuropathology of adult HIV infection. Rev Neurol (Paris) 154: 816–829.

    CAS  Google Scholar 

  • Berger JR, Nath A, Greenberg RN, Andersen AH, Greene RA, Bognar A, Avison MJ (2000). Cerebrovascular changes in the basal ganglia with HIV dementia. Neurology 54: 921–926.

    CAS  PubMed  Google Scholar 

  • Brew BJ, Rosenblum M, Cronin K, Price RW (1995). AIDS dementia complex and HIV-1 brain infection: clinical-virological correlations [see comments]. Ann Neurol 38: 563–570.

    Article  CAS  PubMed  Google Scholar 

  • Budka H, Costanzi G, Cristina S, Lechi A, Parravicini C, Trabattoni R, Vago L (1987). Brain pathology induced by infection with the human immunodeficiency virus (HIV). A histological, immunocytochemical, and electron microscopical study of 100 autopsy cases. Acta Neuropathol 75: 185–198.

    Article  CAS  PubMed  Google Scholar 

  • Burger DM, Boucher CA, Meenhorst PL, Kraayeveld CL, Portegies P, Mulder JW, Hoetelmans RM, Beijnen JH (1997). HIV-1 RNA levels in the cerebrospinal fluid may increase owing to damage to the blood-brain barrier. Antivir Ther 2: 113–117.

    CAS  PubMed  Google Scholar 

  • Chang L, Ernst T, Leonido-Yee M, Walot I, Singer E (1999a). Cerebral metabolite abnormalities correlate with clinical severity of HIV-1 cognitive motor complex. Neurology 52: 100–108.

    CAS  PubMed  Google Scholar 

  • Chang L, Ernst T, Leonido-Yee M, Witt M, Speck O, Walot I, Miller EN (1999b). Highly active antiretroviral therapy reverses brain metabolite abnormalities in mild HIV dementia. Neurology 53: 782–789.

    CAS  PubMed  Google Scholar 

  • Cherner M, Masliah E, Ellis RJ, Marcotte TD, Moore DJ, Grant I, Heaton RK (2002). Neurocognitive dysfunction predicts postmortem findings of HIV encephalitis. Neurology 59: 1563–1567.

    CAS  PubMed  Google Scholar 

  • Cinque P, Vago L, Ceresa D, Mainini F, Terreni MR, Vagani A, Torri W, Bossolasco S, Lazzarin A (1998). Cerebrospinal fluid HIV-1 RNA levels: correlation with HIV encephalitis. AIDS 12: 389–394.

    Article  CAS  PubMed  Google Scholar 

  • Clifford DB, McArthur JC, Schifitto G, Kieburtz K, McDermott MP, Letendre S, Cohen BA, Marder K, Ellis RJ, Marra CM (2002). A randomized clinical trial of CPI-1189 for HIV-associated cognitive-motor impairment. Neurology 59: 1568–1573.

    CAS  PubMed  Google Scholar 

  • Conant K, McArthur JC, Griffin DE, Sjulson L, Wahl LM, Irani DN (1999). Cerebrospinal fluid levels of MMP-2, 7, and 9 are elevated in association with human immunodeficiency virus dementia. Ann Neurol 46: 391–398.

    Article  CAS  PubMed  Google Scholar 

  • Deutsch R, Ellis RJ, McCutchan JA, Marcotte TD, Letendre S, Grant I (2001). AIDS-associated mild neurocognitive impairment is delayed in the era of highly active antiretroviral therapy. AIDS 15: 1898–1899.

    Article  CAS  PubMed  Google Scholar 

  • Dhawan S, Weeks BS, Soderland C, Schnaper HW, Toro LA, Asthana SP, Hewlett IK, Stetler-Stevenson WG, Yamada SS, Yamada KM, et al (1995). HIV-1 infection alters monocyte interactions with human microvascular endothelial cells. J Immunol 154: 422–432.

    CAS  PubMed  Google Scholar 

  • Dore GJ, Correll PK, Li Y, Kaldor JM, Cooper DA, Brew BJ (1999). Changes to AIDS dementia complex in the era of highly active antiretroviral therapy. AIDS 13: 1249–1253.

    Article  CAS  PubMed  Google Scholar 

  • Ernst T, Itti E, Itti L, Chang L (2000). Changes in cerebral metabolism are detected prior to perfusion changes in early HIV-CMC: A coregistered (1)H MRS and SPECT study. J Magn Reson Imaging 12: 859–865.

    Article  CAS  PubMed  Google Scholar 

  • Falangola MF, Hanly A, Galvao Castro B, Petito CK (1995). HIV infection of human choroid plexus: a possible mechanism of viral entry into the CNS. J Neuropathol Exp Neurol 54: 497–503.

    Article  CAS  PubMed  Google Scholar 

  • Fujimura RK, Goodkin K, Petito CK, Douyon R, Feaster DJ, Concha M, Shapshak P (1997). HIV-1 proviral DNA load across neuroanatomic regions of individuals with evidence for HIV-1-associated dementia. J Acquir Immune Defic Syndr Hum Retrovirol 16: 146–152.

    CAS  PubMed  Google Scholar 

  • Gisolf EH, van Praag RM, Jurriaans S, Portegies P, Goudsmit J, Danner SA, Lange JM, Prins JM (2000). Increasing cerebrospinal fluid chemokine concentrations despite undetectable cerebrospinal fluid HIV RNA in HIV-1-infected patients receiving antiretroviral therapy. J Acquir Immune Defic Syndr 25: 426–433.

    Article  CAS  PubMed  Google Scholar 

  • Gray F, Lescs MC, Keohane C, Paraire F, Marc B, Durigon M, Gherardi R (1992). Early brain changes in HIV infection: neuropathological study of 11 HIV seropositive, non-AIDS cases. J Neuropathol Exp Neurol 51: 177–185.

    Article  CAS  PubMed  Google Scholar 

  • Hickey WF (1999). Leukocyte traffic in the central nervous system: the participants and their roles. Semin Immunol 11: 125–137.

    Article  CAS  PubMed  Google Scholar 

  • Hofman FM, Dohadwala MM, Wright AD, Hinton DR, Walker SM (1994). Exogenous tat protein activates central nervous system-derived endothelial cells. J Neuroimmunol 54: 19–28.

    Article  CAS  PubMed  Google Scholar 

  • Hurwitz AA, Berman JW, Lyman WD (1994). The role of the blood-brain barrier in HIV infection of the central nervous system. Adv Neuroimmunol 4: 249–256.

    Article  CAS  PubMed  Google Scholar 

  • Jones MV, Bell JE, Nath A (2000). Immunolocalization of HIV envelope gp120 in HIV encephalitis with dementia. AIDS 14: 2709–2713.

    Article  CAS  PubMed  Google Scholar 

  • Kandanearatchi A, Williams B, Everall IP (2003). Assessing the efficacy of highly active antiretroviral therapy in the brain. Brain Pathol 13: 104–110.

    Article  PubMed  Google Scholar 

  • Kelder W, McArthur JC, Nance Sproson T, McClernon D, Griffin DE (1998). Beta-chemokines MCP-1 and RANTES are selectively increased in cerebrospinal fluid of patients with human immunodeficiency virus-associated dementia. Ann Neurol 44: 831–835.

    Article  CAS  PubMed  Google Scholar 

  • Kure K, Llena JF, Lyman WD, Soeiro R, Weidenheim KM, Hirano A, Dickson DW (1991). Human immunodeficiency virus-1 infection of the nervous system: an autopsy study of 268 adult, pediatric, and fetal brains. Hum Pathol 22: 700–710.

    Article  CAS  PubMed  Google Scholar 

  • Langford TD, Letendre SL, Larrea GJ, Masliah E (2003). Changing patterns in the neuropathogenesis of HIV during the HAART era. Brain Pathol 13: 195–210.

    Article  CAS  PubMed  Google Scholar 

  • Laubenberger J, Haussinger D, Bayer S, Thielemann S, Schneider B, Mundinger A, Hennig J, Langer M (1996). HIV-related metabolic abnormalities in the brain: depiction with proton MR spectroscopy with short echo times. Radiology 199: 805–810.

    CAS  PubMed  Google Scholar 

  • Levy JA (1997). HIV neuropathogenesis. J NeuroVirol 3: S14-S15.

    PubMed  Google Scholar 

  • Liuzzi GM, Mastroianni CM, Santacroce MP, Fanelli M, D’Agostino C, Vullo V, Riccio P (2000). Increased activity of matrix metalloproteinases in the cerebrospinal fluid of patients with HIV-associated neurological diseases. J NeuroVirol 6: 156–163.

    Article  CAS  PubMed  Google Scholar 

  • Masliah E, DeTeresa RM, Mallory ME, Hansen LA (2000). Changes in pathological findings at autopsy in AIDS cases for the last 15 years. AIDS 14: 69–74.

    Article  CAS  PubMed  Google Scholar 

  • McArthur JC, McClernon DR, Cronin MF, Nance Sproson TE, Saah AJ, St Clair M, Lanier ER (1997). Relationship between human immunodeficiency virus-associated dementia and viral load in cerebrospinal fluid and brain [see comments]. Ann Neurol 42: 689–698.

    Article  CAS  PubMed  Google Scholar 

  • Meyerhoff DJ, Weiner MW, Fein G (1996). Deep gray matter structures in HIV infection: a proton MR spectroscopic study. AJNR Am J Neuroradiol 17: 973–978.

    CAS  PubMed  Google Scholar 

  • Moses AV, Bloom FE, Pauza CD, Nelson JA (1993). Human immunodeficiency virus infection of human brain capillary endothelial cells occurs via a CD4/ galactosylceramide-independent mechanism. Proc Natl Acad Sci USA 90: 10474–10478.

    Article  CAS  PubMed  Google Scholar 

  • Neuen-Jacob E, Arendt G, Wendtland B, Jacob B, Schneeweis M, Wechsler W (1993). Frequency and topographical distribution of CD68-positive macrophages and HIV-1 core proteins in HIV-associated brain lesions. Clin Neuropathol 12: 315–324.

    CAS  PubMed  Google Scholar 

  • Neuenburg JK, Brodt HR, Herndier BG, Bickel M, Bacchetti P, Price RW, Grant RM, Schlote W (2002). HIV-related neuropathology, 1985 to 1999: rising prevalence of HIV encephalopathy in the era of highly active antiretroviral therapy. J Acquir Immune Defic Syndr 31: 171–177.

    PubMed  Google Scholar 

  • Nottet HS (1999). Interactions between macrophages and brain microvascular endothelial cells: role in pathogenesis of HIV-1 infection and blood-brain barrier function. J NeuroVirol 5: 659–669.

    Article  CAS  PubMed  Google Scholar 

  • Petito CK, Cash KS (1992). Blood-brain barrier abnormalities in the acquired immunodeficiency syndrome: immunohistochemical localization of serum proteins in postmortem brain. Ann Neurol 32: 658–666.

    Article  CAS  PubMed  Google Scholar 

  • Power C, Kong PA, Crawford TO, Wesselingh S, Glass JD, McArthur JC, Trapp BD (1993). Cerebral white matter changes in acquired immunodeficiency syndrome dementia: alterations of the blood-brain barrier. Ann Neurol 34: 339–350.

    Article  CAS  PubMed  Google Scholar 

  • Power C, Selnes OA, Grim JA, McArthur JC (1995). HIV Dementia Scale: a rapid screening test. J Acquir Immune Defic Syndr Hum Retrovirol 8: 273–278.

    Article  CAS  PubMed  Google Scholar 

  • Price RW, Brew BJ (1988). The AIDS dementia complex. J Infect Dis 158: 1079–1083.

    CAS  PubMed  Google Scholar 

  • Pumarola Sune T, Navia BA, Cordon Cardo C, Cho ES, Price RW (1987). HIV antigen in the brains of patients with the AIDS dementia complex. Ann Neurol 21: 490–496.

    Article  CAS  PubMed  Google Scholar 

  • Robertson K, Fiscus S, Kapoor C, Robertson W, Schneider G, Shepard R, Howe L, Silva S, Hall C (1998). CSF, plasma viral load and HIV associated dementia. J NeuroVirol 4: 90–94.

    Article  CAS  PubMed  Google Scholar 

  • Sacktor N, Lyles RH, Skolasky R, Kleeberger C, Selnes OA, Miller EN, Becker JT, Cohen B, McArthur JC (2001). HIV-associated neurologic disease incidence changes: Multicenter AIDS Cohort Study, 1990–1998. Neurology 56: 257–260.

    CAS  PubMed  Google Scholar 

  • Sacktor N, McDermott MP, Marder K, Schifitto G, Selnes OA, McArthur JC, Stern Y, Albert S, Palumbo D, Kieburtz K, De Marcaida JA, Cohen B, Epstein L (2002). HIV-associated cognitive impairment before and after the advent of combination therapy. J NeuroVirol 8: 136–142.

    Article  PubMed  Google Scholar 

  • Salvan AM, Vion-Dury J, Confort-Gouny S, Nicoli F, Lamoureux S, Cozzone PJ (1997a). Brain proton magnetic resonance spectroscopy in HIV-related encephalopathy: identification of evolving metabolic patterns in relation to dementia and therapy. AIDS Res Hum Retroviruses 13: 1055–1066.

    Article  CAS  PubMed  Google Scholar 

  • Salvan AM, Vion-Dury J, Confort-Gouny S, Nicoli F, Lamoureux S, Cozzone PJ (1997b). Cerebral metabolic alterations in human immunodeficiency virus-related encephalopathy detected by proton magnetic resonance spectroscopy. Comparison between sequences using short and long echo times. Invest Radiol 32: 485–495.

    Article  CAS  PubMed  Google Scholar 

  • Schmitt FA, Bigley JW, McKinnis R, Logue PE, Evans RW, Drucker JL (1988). Neuropsychological outcome of zidovudine (AZT) treatment of patients with AIDS and AIDS-related complex. N Engl J Med 319: 1573–1578.

    Article  CAS  PubMed  Google Scholar 

  • Schmitt FA, Wetherby M, Stern Y (1997). Neuropsychological changes in human immunodeficiency virus infection. In: AIDS and the nervous system (2nd ed). Berger JR, Levy RM (eds). Philadelphia: Lippincott-Raven. 401–417.

    Google Scholar 

  • Seilhean D, Dzia-Lepfoundzou A, Sazdovitch V, Cannella B, Raine CS, Katlama C, Bricaire F, Duyckaerts C, Hauw JJ (1997). Astrocytic adhesion molecules are increased in HIV-1-associated cognitive/motor complex. Neuropathol Appl Neurobiol 23: 83–92.

    Article  CAS  PubMed  Google Scholar 

  • Silver NC, Good CD, Sormani MP, MacManus DG, Thompson AJ, Filippi M, Miller DH (2001a). A modified protocol to improve the detection of enhancing brain and spinal cord lesions in multiple sclerosis. J Neurol 248: 215–224.

    Article  CAS  PubMed  Google Scholar 

  • Silver NC, Tofts PS, Symms MR, Barker GJ, Thompson AJ, Miller DH (2001b). Quantitative contrast-enhanced magnetic resonance imaging to evaluate blood-brain barrier integrity in multiple sclerosis: a preliminary study. Mult Scler 7: 75–82.

    CAS  PubMed  Google Scholar 

  • Smith TW, DeGirolami U, Henin D, Bolgert F, Hauw JJ (1990). Human immunodeficiency virus (HIV) leukoencephalopathy and the microcirculation. J Neuropathol Exp Neurol 49: 357–370.

    Article  CAS  PubMed  Google Scholar 

  • Soontornniyomkij V, Nieto Rodriguez JA, Martinez AJ, Kingsley LA, Achim CL, Wiley CA (1998). Brain HIV burden and length of survival after AIDS diagnosis. Clin Neuropathol 17: 95–99.

    CAS  PubMed  Google Scholar 

  • Tracey I, Carr CA, Guimaraes AR, Worth JL, Navia BA, Gonzalez RG (1996). Brain choline-containing compounds are elevated in HIV-positive patients before the onset of AIDS dementia complex: a proton magnetic resonance spectroscopic study [published erratum appears in Neurology 1996 Jun;46(6):1787]. Neurology 46: 783–788.

    CAS  PubMed  Google Scholar 

  • Tracey I, Hamberg LM, Guimaraes AR, Hunter G, Chang I, Navia BA, Gonzalez RG (1998). Increased cerebral blood volume in HIV-positive patients detected by functional MRI. Neurology 50: 1821–1826.

    CAS  PubMed  Google Scholar 

  • Tyor WR, Glass JD, Griffin JW, Becker PS, McArthur JC, Bezman L, Griffin DE (1992). Cytokine expression in the brain during the acquired immunodeficiency syndrome. Ann Neurol 31: 349–360.

    Article  CAS  PubMed  Google Scholar 

  • van Gorp WG, Miller EN, Marcotte TD, Dixon W, Paz D, Selnes O, Wesch J, Becker JT, Hinkin CH, Mitrushina M, et al (1994). The relationship between age and cognitive impairment in HIV-1 infection: findings from the Multicenter AIDS Cohort Study and a clinical cohort. Neurology 44: 929–935.

    PubMed  Google Scholar 

  • Weis S, Haug H, Budka H (1996). Vascular changes in the cerebral cortex in HIV-1 infection: I. A morphometric investigation by light and electron microscopy. Clin Neuropathol 15: 361–366.

    CAS  PubMed  Google Scholar 

  • Wiley CA, Soontornniyomkij V, Radhakrishnan L, Masliah E, Mellors J, Hermann SA, Dailey P, Achim CL (1998). Distribution of brain HIV load in AIDS. Brain Pathol 8: 277–284.

    Article  CAS  PubMed  Google Scholar 

  • Woodman SE, Benveniste EN, Nath A, Berman JW (1999). Human immunodeficiency virus type 1 TAT protein induces adhesion molecule expression in astrocytes. J NeuroVirol 5: 678–684.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, University of Kentucky Medical Center, Lexington, Kentucky, USA

    Malcolm J. Avison, Avindra Nath, Frederick A. Schmitt, Rodney A. Bales, As’ad Ethisham & Joseph R. Berger

  2. Department of Internal Medicine, University of Kentucky Medical Center, Lexington, Kentucky, USA

    Richard N. Greenberg

  3. Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky Medical Center, Lexington, Kentucky, USA

    Robin Greene-Avison

  4. Department of Neurology, Johns-Hopkins Medical School, Baltimore, Maryland, USA

    Avindra Nath

  5. Departments of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA

    Malcolm J. Avison

  6. Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA

    Malcolm J. Avison

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  1. Malcolm J. Avison
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  2. Avindra Nath
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Avison, M.J., Nath, A., Greene-Avison, R. et al. Inflammatory changes and breakdown of microvascular integrity in early human immunodeficiency virus dementia. Journal of NeuroVirology 10, 223–232 (2004). https://doi.org/10.1080/13550280490463532

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