Research Article - Journal of Drug and Alcohol Research ( 2021) Volume 10, Issue 11
The Impact of Addictive Drugs on HIV ImmunopathogenesisXiaochun Li1, Wei Jiang7,12, Lei Huang11, Aimee McRae-Clark6, Ren Lang10, Danielle Macedo9, Jingjing Wang8, Azizul Haque7, Amanda Wagner6, Lishomwa C. Ndhlovu5, Binhua Ling4, Yifang Wen3, Wenwen He2 and Davide Amato13*
2The Sixth People�s Hospital of Xinjiang, Clinical Laboratory Center, China
3The Sixth People�s Hospital of Xinjiang, Hepatitis Treatment Center, China
4Department of Microbiology and Immunology, Tulane University, USA
5Department of Infectious Diseases, Weill Cornell Medical College, USA
6Department of Psychiatry and Behavioral Sciences, The Medical University of South Carolina, USA
7Department of Microbiology and Immunology, The Medical University of South Carolina, USA
8Department of Immunology, Flinders University, Australia
9Department of Physiology and Pharmacology, Universidade Federal do Ceara, Brazil
10Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, China
11Treatment and Research Center for Infectious Diseases, The 302 Hospitals of PLA, China
12Department of Medicine, The Medical University of South Carolina, USA
13Department of Neurosciences, The Medical University of South Carolina, USA
Davide Amato, Department of Neurosciences, The Medical University of South Carolina, USA, Email: email@example.com
Received: 09-Nov-2021;Accepted Date: Nov 23, 2021; Published: 30-Dec-2021
Substance Use Disorder (SUD) is associated with neurocognitive disorders as well as with alterations of the immune system function. Different addictive drugs exhibit differences in neurocognitive performance and immune response against inflammation. In HIV disease, SUD is associated with increased HIV susceptibility and infection, HIV replication, blunted CD4+ T cell reconstitution under viral suppressive Antiretroviral Therapy (ART), perturbations of immune system and accelerated HIV-associated neurologic disorders (HAND). To date, extensive studies have been done to understand high incidence of HAND in HIV disease, but the exact mechanisms are not completely understood, especially of long term ART and viral suppression settings. We have reviewed work on the impact of addictive drugs on HAND in HIV immunopathogenesis
HIV; Substance use disorder; CD4+ T cells; Neurocognition; HAND; Antiretroviral therapy
• Substance use disorder is associated with neuroinflammation and neurocognitive disorders.
• In HIV disease, addictive drug abuse is associated with increased HIV susceptibility and infection.
• Bacterial product translocation is a potential mechanism through with substance of abuse can aggravate HIV impact on overall clinical course and brain function.
• The use of animal models can be fundamental to gain insight into the mechanisms underlying HIV and neurocognitive disorders comorbidity.
HIV-Associated Neurocognitive Disorder (HAND) persists in people living with HIV infection (PLWH) despite viral suppression by ART [1-4]. Brain abnormalities are observed in 30%-50% of PLWH and are known to be driven partly by systemic neuroinflammation [5-11]. In PLWH, impaired amygdala responses were associated with increased neurocognitive symptoms such as depression, anxiety, and reduced emotional awareness. Reduced putamen size was associated with impaired motor function in HIV.
The most commonly abused addictive drugs by HIV-infected individuals include cannabis, Cocaine, morphine, methamphetamine, heroin, and amphetamine. The use of addictive drugs is associated with increased incidence of HIV infection, neurocognitive disorders, HIV replication, morbidity and mortality compared to non-HIV drug users and HIV-infected non users [1-4]. Currently, most patients in the US receive viral suppressive Antiretroviral Therapy (ART) treatment to suppress viral replication and control disease progression. However, Substance Use Disorders (SUD) in HIV patients could be a main factor underlying low adherence to ART treatment, uncontrolled viremia, and increased chronic inflammation diseasmay account for blunted CD4+ T cell reconstitution [5-8]. Thus, HIV infected individuals with comorbid addictive drug use disorders may characterize a distinct subgroup of patients who will suffer a more severe clinical course [9- 13]. To date, extensive studies have been done to understand high incidence of HIV Associated Neurologic Disorders (HAND) in HIV disease, but the exact mechanisms are not completely understood, especially of long term ART and viral suppression settings.
The Impact of Addictive Drug on HIV Viral Replication
It is challenging to study the impact of addictive drugs on immune perturbations in HIV as several confounding factors are involved (e.g., ART treatment adherence and viral replication levels). ART treatment adherence and viral replication levels are often related to addictive drug abuse, suggesting a mechanism of addictive drug mediated immune perturbations and faster disease progression in HIV [14,15]. Moreover, factors including single or multiple drug use, duration of drug use, and route of drug use contribute to drug associated disease progression. Previous studies showed that both substance abuse and heightened levels of T cell activation are associated with poor CD4+ T cell recovery under ART in HIV disease; and drug use associated low adherence to ART treatment and loss of virology control mainly account for poor immune reconstitution in these patients [16-20]. Nevertheless, previous studies show that treatment of cocaine, cannabis, or opiates impacts HIV viral replication using animal models or using human cells in vitro [21-23]. Notably, treatment with 200 mg/L-1000 mg/L of cocaine results in CD4+ T cell death in vitro, implies that cocaine may have a direct role in poor CD4+ T cell recovery and uncontrolled HIV replication . In addition, increased susceptibility to HIV infection and HIV reservoir have been observed in cultured brain cells treated with cocaine [25,26]. Thus, SUD is associated with loss of viral control, accelerated disease transmission and progression, mortality, and morbidity.
The Impact of Addictive Drug on Systemic Immunities in HIV Disease
It is critical to study the impact of addictive drugs on systemic immune perturbations in HIV disease under viral suppressive ART treatment. Previous investigations have shown that HIV-infected patients with SUD have poor CD4+ T cell recovery, accelerated disease progression, and mortality [6,27]. Monocyte and macrophage activation play a key role in persistent immune activation and inflammation, as well as increased incidence of cardiovascular diseases in HIV and neuro HIV infection [28-31]. Soluble CD163 and CD14 can be produced by monocytes in response to LPS stimulation [7,8,32-37]. SUD is associated with increased plasma levels of soluble CD163 and CD14, suggesting cell activation and oxidative stress of monocytes or macrophages [32-35]. Studies from Brenchley group and our group show that HIV/SIV infection results in intestinal barrier impairment, systemic bacterial product translocation, and as a consequences of cell activation, apoptosis and persistent inflammation [38-41]. HIV has been reported to have a direct effect on epithelial cells; HIV Tat and gp120 proteins decrease tight junction (claudin 1, 2, 4, occludin and ZO-1) protein expression using human primary cells and cell lines in vitro [42,43].
The activation of monocytes or macrophages may result from increased gut permeability and microbial translocation in drug users in HIV disease. Some factors have the potential to affect the microbial translocation and cell activation, the route of drug use and microbiome. Ingestion of drug most likely affects the intestinal tract; inhalation of drug most likely affects lung and respiratory tract; and vascular injection of drug most likely affects the whole system. The translocated bacterial products may also play a role in cell activation, as some inflammatory strain of bacterial products may promote heightened inflammation and non-inflammatory or commensal strain of bacterial products may inhibit inflammation. Nonetheless, the exact mechanisms on how drug abuse mediated CD4+ T cell decline, persistent immune activation and inflammation even in HIV-infected patients with long term viral suppressive ART treatment remain unclear.
The Impact of Addictive Drug on Neuro-impairment in HIV Disease
There are about one third of ART-treated HIV-infected patients who exhibit HAND under viral suppressive ART treatment . This may occur via alteration of blood brain barrier by addictive drugs abuse allowing faster replication of HIV virus infection in the brain . Cocaine has been shown to induce macrophage and microglia activation directly, resulting in neuro-inflammation and neurotoxicity and uncontrolled HIV viral replication [46,47]. Moreover, increased intestinal and blood brain barrier permeability has been reported in cells or animals after treatment with cocaine, opioid, and morphine . However, decreased blood brain barrier permeability has been reported in rat models after treatment with cannabis . Because of permeable barriers, microbial translocation promotes cell activation, migration and induce pro-inflammatory cytokine (e.g., TNF-α) production, resulting in the activation of microglia, astrocytes, and perivascular macrophages and neuroinflammation. Furthermore, the cytokines and chemokines (e.g., IL-6, MCP-1, MIP-1) produced by these activated CNS cells recruit circulating lymphocytes to CNS and induce in neuronal injury . Importantly, microbial TLR-related proinflammatory cytokines such as IL-17a, IL-10, IL-6, IL-8, TNF-α, IP-10, MIP-α, and IL- 12/IL-23p40 are increased in the CNS in patients with neuro- cognitive impairment [44,51]. These cytokines can be produced by microglia and astrocyte activation in response to TLR4 ligation and are associated with HIV HAND without being further stratified by use of a particular drug [52- 56]. Moreover, plasma levels of soluble CD163 and CD14 are associated with neurocognitive disorders in HIV diseases, another evidence of monocyte activation in response to bacterial products [57-59]. These lines of evidence strongly suggest that the host defense to foreign antigens may play a double edged role: They are essential to control invading pathogens, but the perturbed systemic or CNS immune responses could be harmful.
Associated brain cell markers such as Neurofilament Light chain protein (NFL) in Cerebrospinal Fluid (CSF) has been shown association with neuronal injury in HIV patients especially with dementia . In ART naïve patients, plasma level of NFL is directly associated with CSF NFL level, indicating a potential non-invasive biomarker for HAND in HIV . In addition, S100B is a calcium binding protein in astrocytes and may associate with neurodegeneration; quinolinic acid, a neuroexcitotoxic metabolite of L-tryptophan, has been found to increase in HAND HIV patients [44,60]. Increased inflammation and acute phase proteins Creative Protein (CRP) and amyloid A (SAA) is associated with HIV patients with cocaine abuse and increased neuro- inflammation .
Neuro-HIV Animal Models
Neuro-HIV animal models have been critical for investigating causality and mechanisms of neuro-HIV disease pathogenesis, evaluating novel therapies along with the interaction of virus with neuroimmune responses and behavior [47,62-64]. Potential confounding factors can be evaluated using animal models including food, gene, environmental, and socio economic factors. HAND includes HIV-Associated Dementia (HAD) Asymptomatic Neurocognitive Impairment (ANI) and Milder Neurocognitive Disorder (MND) . HAD exhibits irreversible neuronal impairment and neurodysfunction; whereas ANI and MND may have reversible physiological and neurodisorders . The incidence of HAD is significantly decreased after introduction of ART treatment, and ANI and MND are the most prevalent neurodisorders in ART treated HIV disease [65,66]. Notably, there are about 50% HIV-infected population who have HAND despite ART treatment. HIV-infected patients with HAND exhibit mild learning and/or memory disturbances, consistent with data from HAND animal models [47, 62-67]. Therefore, HAND animal models can help to evaluate behavioral performance similar to neurocognitive disorders in HIV patients. Furthermore, neuro histopathological parameters may not present in ANI and MND, which rely on both neuropathological parameters and behavioral assessments. It is important to have a window of plasticity when animal models are used to evaluate a novel treatment to reverse neurological impairments such as memory performance.
In animal models memory can be quantified and assessed using the Object Recognition Test (ORT), which evaluates the ability to remember and recognize a previously presented object and discriminate it from a new one. There will be a new object if the animal has a successful memory retention [68,69]. Thus HAND animal models can be used to characterize learning and memory, as well as the alteration of brain cellular activity and cognition. The limitation of the HAND mouse model is that they cannot perfectly represent HIV patients with HAND. However, they serve as an excellent preclinical model for novel treatment and for pathogenetic studies. Notably, a reliable marker of human HAND and autopsy studies are critical for us to define a more precise model. Our goal is to eliminate HIV reservoir and HIV infection in the brain. The HAND animal models may be applied to investigate other diseases with neuro- cognitive disorders.
In summary, drugs of abuse combined with HIV infection accelerate systemic immune perturbations and neurological disorders leading to increase mortality and morbidity. Animal models are warned to be a suitable approach to characterize the underlying mechanisms of HIV-SUD comorbidity.
We thank Ms. Ariana Angelis for assistance and comments. This work was supported by NIH grants MH116844 (Ling), CA129560 (Haque), DA038240 (McRae-Clark), MH104141 (Ndhlovu), MH112457 (Ndhlovu), the Australian National Health and Medical Research Council Early Career Fellowship grant 1090759 (Wang), Deutsche Forschungsgemeinschaft (AM 488/1-2) and the Brain & Behavior Research Foundation NARSAD Young Investigator Grant (Amato), Beijing Natural Science Foundation (Grant No.7152063, Lang) and Scientific Research Common Program of Beijing Municipal Commission of Education (KM2016100250017, Lang), and the National Natural Science Foundation of China (81772185, Huang). Translational Sciences of the National Institutes of Health under Award Number UL1TR001450 (the pilot grant, W.J.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
- M. K. Baum, A. Camp, J. B. Page, Recruitment, Follow-Up and characteristics of HIV infected adults who use illicit drugs in Southern Africa, J Drug Abuse, 1 (2015).
- M. Tyagi, J. Weber, M. Bukrinsky, G. L. Simon, The effects of cocaine on HIV transcription, J Neurovirol, 22 (2016), 261-274.
- R. J. Ellis, M. E. Childers, M. Cherner, Increased human immunodeficiency virus loads in active methamphetamine users are explained by reduced effectiveness of antiretroviral therapy, J Infect Dis, 188 (2003), 1820-1826.
- N. Fairbairn, T. Kerr, M. J. Milloy, R. Zhang, J. Montaner, et al. Crystal methamphetamine injection predicts slower HIV RNA suppression among injection drug users, Addict Behav, 36 (2011), 762-763.
- J. A. Cook, D. D. Grey, J. K. Burke-Miller, Illicit drug use, depression and their association with highly active antiretroviral therapy in HIV-positive women, Drug Alcohol Depend, 89 (2007), 74-81.
- R. C. Passaro, J. Pandhare, H. Z. Qian, C. Dash, The complex interaction between methamphetamine abuse and HIV-1 Pathogenesis, J Neuroimmune Pharmacol, 10 (2015), 477-486.
- J. Meng, H. Yu, J. Ma, Morphine induces bacterial translocation in mice by compromising intestinal barrier function in a TLR-dependent manner, PLoS One, 8 (2013), e54040.
- S. Banerjee, G. Sindberg, F. Wang, Opioid-induced gut microbial disruption and bile dysregulation leads to gut barrier compromise and sustained systemic inflammation, Mucosal Immunol, 2016.
- I. C. Anthony, J. C. Arango, B. Stephens, P. Simmonds, J. E. Bell, The effects of illicit drugs on the HIV infected brain, Front Biosci, 13 (2008), 1294-1307.
- J. E. Bell, R. P. Brettle, A. Chiswick, P. Simmonds, HIV encephalitis, proviral load and dementia in drug users and homosexuals with AIDS, Effect of neocortical involvement, Brain, 121 (1998), 2043-2052.
- P. S. Silverstein, A. Shah, R. Gupte, Methamphetamine toxicity and its implications during HIV-1 infection, J Neurovirol, 17 (2011), 401-415.
- P. J. Gaskill, T. M. Calderon, J. S. Coley, J. W. Berman. Drug induced increases in CNS dopamine alter monocyte, macrophage and T cell functions: Implications for HAND, J Neuroimmune Pharmacol, 8 (2013), 621-642.
- V. J. Meyer, D. M. Little, D. A. Fitzgerald, Crack cocaine use impairs anterior cingulate and prefrontal cortex function in women with HIV infection, J Neurovirol, 20 (2014), 352-361.
- J. T. Parsons, W. J. Kowalczyk, M. Botsko, J. Tomassilli, S. A. Golub. Aggregate versus day level association between methamphetamine use and HIV medication non-adherence among gay and bisexual men, AIDS Behav, 17 (2013), 1478-1487.
- C. Marquez, S. J. Mitchell, C. B. Hare, M. John, J. D. Klausner, Methamphetamine use, sexual activity, patient-provider communication, and medication adherence among HIV-infected patients in care, San Francisco 2004-2006, AIDS Care, 21 (2009), 575-582.
- H. Valdez, E. Connick, K. Y. Smith, Limited immune restoration after 3 years' suppression of HIV-1 replication in patients with moderately advanced disease, AIDS, 16 (2002), 1859-1866.
- P. W. Hunt, J. N. Martin, E. Sinclair, T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy, J Infect Dis, 187 (2003), 1534-1543.
- A. Landay, L. Benning, J. Bremer, Correlates of immune activation marker changes in human immunodeficiency virus (HIV)-seropositive and high-risk HIV-seronegative women who use illicit drugs, J Infect Dis, 188, (2003), 209-218.
- A. Cescon, K. Chan, J. M. Raboud, Significant differences in clinical outcomes between HIV-hepatitis C virus coinfected individuals with and without injection drug use history, AIDS, 28 (2014), 121-127.
- F. N. Engsig, R. Zangerle, O. Katsarou, Long-term mortality in HIV-positive individuals virally suppressed for >3 years with incomplete CD4 recovery, Clin Infect Dis, 58 (2014), 1312-1321.
- X. Wang, W. Z. Ho, Drugs of abuse and HIV infection/replication: Implications for mother-fetus transmission, Life Sci, 88 (2011), 972-979.
- C. K. Mantri, J. V. Mantri, J. Pandhare, C. Dash, Methamphetamine inhibits HIV-1 replication in CD4+ T cells by modulating anti-HIV-1 miRNA expression, Am J Pathol, 184 (2014), 92-100.
- S. Suzuki, M. P. Carlos, L. F. Chuang, J. V. Torres, R. H. Doi, et al. Methadone induces CCR5 and promotes AIDS virus infection, FEBS Lett, 519 (2002), 173-177.
- J. Pandhare, A. B. Addai, C. K. Mantri, Cocaine enhances HIV-1-induced CD4(+) T-cell apoptosis: Implications in disease progression in cocaine-abusing HIV-1 patients, Am J Pathol, 184 (2014), 927-936.
- S. G. Kim, J. B. Jung, D. Dixit, Cocaine exposure enhances permissiveness of quiescent T cells to HIV infection, J Leukoc Biol, 94 (2013), 835-843.
- C. K. Mantri, J. Pandhare-Dash, J. V. Mantri, C. C. Dash. Cocaine enhances HIV-1 replication in CD4+ T cells by down-regulating MiR-125b, PLoS One, 7 (2012), e51387.
- W. Jiang, Z. Luo, L. Martin, Drug use is associated with anti-CD4 IgG-mediated CD4+ T cell death and poor CD4+ T cell recovery in viral-suppressive HIV-infected individuals under antiretroviral therapy, Curr HIV Res, 2018.
- N. T. Funderburg, D. A. Zidar, C. Shive, Shared monocyte subset phenotypes in HIV-1 infection and in uninfected subjects with acute coronary syndrome, Blood, 120 (2012), 4599-4608.
- R. A. McKibben, J. B. Margolick, S. Grinspoon, Elevated levels of monocyte activation markers are associated with subclinical atherosclerosis in men with and those without HIV infection, J Infect Dis, 211 (2015), 1219-1228.
- B. M. Imp, L. H. Rubin, P. C. Tien, Monocyte Activation is associated with worse cognitive performance in HIV infected women with virologic suppression, J Infect Dis, 215 (2017), 114-121.
- M. Veenstra, R. Leon-Rivera, M. Li, L. Gama, J. E. Clements, J. W. Berman, Mechanisms of CNS viral seeding by HIV(+) CD14(+) CD16(+) Monocytes: Establishment and reseeding of viral reservoirs contributing to HIV-Associated neurocognitive disorders, M Bio, 8 (2017).
- S. H. Ahmed, R. Lutjens, L. D. Van-der-Stap, Gene expression evidence for remodeling of lateral hypothalamic circuitry in cocaine addiction, Proc Natl Acad Sci USA, 102 (2005), 11533-11538.
- M. Piechota, M. Korostynski, W. Solecki, The dissection of transcriptional modules regulated by various drugs of abuse in the mouse striatum, Genome Biol, 11 (2010), R48.
- P. Dalvi, K. Wang, J. Mermis, HIV-1/cocaine induced oxidative stress disrupts tight junction protein-1 in human pulmonary microvascular endothelial cells: Role of Ras/ERK1/2 pathway, PLoS One, 9 (2014), e85246.
- H. F. Poon, L. Abdullah, M. A. Mullan, M. J. Mullan, F. C. Crawford, Cocaine-induced oxidative stress precedes cell death in human neuronal progenitor cells, Neurochem Int, 50 (2007), 69-73.
- G. M. Sindberg, U. Sharma, S. Banerjee, An infectious murine model for studying the systemic effects of opioids on early HIV pathogenesis in the gut, J Neuroimmune Pharmacol, 10 (2015), 74-87.
- J. Meng, G. M. Sindberg, S. Roy, Disruption of gut homeostasis by opioids accelerates HIV disease progression, Front Microbiol, 6 (2015), 643.
- N. Funderburg, A. A. Luciano, W. Jiang, B. Rodriguez, S. F. Sieg, et al. Toll-like receptor ligands induce human T cell activation and death, a model for HIV pathogenesis, PLoS One, 3 (2008), e1915.
- W. Jiang, M. M. Lederman, P. Hunt, Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection, J Infect Dis, 199 (2009), 1177-1185.
- M. M. Lederman, L. Calabrese, N. T. Funderburg, Immunologic failure despite suppressive antiretroviral therapy is related to activation and turnover of memory CD4 cells, J Infect Dis, 204 (2011), 1217-1226.
- W. Jiang, S. A. Younes, N. T. Funderburg, Cycling memory CD4+ T cells in HIV disease have a diverse T cell receptor repertoire and a phenotype consistent with bystander activation, J Virol, 88 (2014), 5369-5380.
- L. Bai, Z. Zhang, H. Zhang, HIV-1 Tat protein alter the tight junction integrity and function of retinal pigment epithelium: An in vitro study, BMC Infect Dis, 8 (2008), 77.
- A. Nazli, O. Chan, W. N. Dobson-Belaire, Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation, PLoS Path, 6 (2010), e1000852.
- P. Rahimian, J. J. He, HIV/neuroAIDS biomarkers, Prog Neurobiol, 2016.
- S. D. Mahajan, R. Aalinkeel, D. E. Sykes, Methamphetamine alters blood brain barrier permeability via the modulation of tight junction expression: Implication for HIV-1 neuropathogenesis in the context of drug abuse, Brain Res, 1203 (2008), 133-148.
- N. K. Dhillon, R. Williams, F. Peng, Cocaine-mediated enhancement of virus replication in macrophages: Implications for human immunodeficiency virus-associated dementia, J Neurovirol, 13 (2007), 483-495.
- I. Kusao, B. Shiramizu, C. Y. Liang, Cognitive performance related to HIV-1-infected monocytes, J Neuropsych Clin Neurosci, 24 (2012), 71-80.
- H. Yao, M. Duan, S. Buch, Cocaine-mediated induction of platelet-derived growth factor: Implication for increased vascular permeability, Blood, 117 (2011), 2538-2547.
- S. Khaksar, M. R. Bigdeli, Anti-excitotoxic effects of cannabidiol are partly mediated by enhancement of NCX2 and NCX3 expression in animal model of cerebral ischemia, Eur J Pharmacol, 794 (2017) 270-279.
- S. Hong, W. A. Banks, Role of the immune system in HIV-associated neuroinflammation and neurocognitive implications, Brain Behav Immun, 45 (2015), 1-12.
- P. Cinque, A. Bestetti, R. Marenzi, Cerebrospinal fluid interferon-gamma-inducible protein 10 (IP-10, CXCL10) in HIV-1 infection, J Neuroimmunol, 168 (2005), 154-163.
- S. M. Lawrence, J. L. Ruoss, J. L. Wynn, IL-17 in neonatal health and disease, Am J Reprod Immunol, 2017.
- I. Tabas, A. H. Lichtman, Monocyte-Macrophages and T Cells in Atherosclerosis, Immunity, 47 (2017), 621-634.
- G. A. Hardy, S. F. Sieg, B. Rodriguez, Desensitization to type I interferon in HIV-1 infection correlates with markers of immune activation and disease progression, Blood, 13 (2009), 5497-5505.
- F. Shimizu, H. Nishihara, Y. Sano, Markedly increased IP-10 production by blood-brain barrier in neuromyelitis optica, PLoS One, 10 (2015), e0122000.
- J. Zimmermann, M. Emrich, M. Krauthausen, IL-17A Promotes Granulocyte Infiltration, Myelin Loss, Microglia Activation, and Behavioral Deficits during Cuprizone-Induced Demyelination, Mol Neurobiol, 55 (2018), 946-957.
- T. H. Burdo, A. Weiffenbach, S. P. Woods, S. Letendre, R. J. Ellis, et al. Elevated sCD163 in plasma but not cerebrospinal fluid is a marker of neurocognitive impairment in HIV infection, AIDS, 27 (2013), 1387-1395.
- B. Shiramizu, J. Ananworanich, T. Chalermchai, Failure to clear intra-monocyte HIV infection linked to persistent neuropsychological testing impairment after first-line combined antiretroviral therapy, J Neurovirol, 18 (2012), 69-73.
- L. A. Ryan, J. Zheng, M. Brester, Plasma levels of soluble CD14 and tumor necrosis factor-alpha type II receptor correlate with cognitive dysfunction during human immunodeficiency virus type 1 infection, J Infect Dis, 184 (2001) 699-706.
- M. P. Heyes, K. Saito, J. S. Crowley, Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease, Brain, 115 (1992), 1249-1273.
- T. Samikkannu, K. V. Rao, A. Y. Arias, HIV infection and drugs of abuse: Role of acute phase proteins, J Neuroinflammation, 10 (2013), 113.
- J. E. Clements, M. Li, L. Gama, The central nervous system is a viral reservoir in simian immunodeficiency virus-infected macaques on combined antiretroviral therapy: A model for human immunodeficiency virus patients on highly active antiretroviral therapy, J Neurovirol, 11 (2005), 180-189.
- B. Anesten, A. Yilmaz, L. Hagberg, Blood-brain barrier integrity, intrathecal immunoactivation, and neuronal injury in HIV, Neurol Neuroimmunol Neuroinflamm, 3 (2016), e300.
- J. B. Honeycutt, P. A. Sheridan, G. K. Matsushima, J. V. Garcia, Humanized mouse models for HIV-1 infection of the CNS, J Neurovirol, 21 (2015), 301-319.
- A. Antinori, G. Arendt, J. T. Becker, Updated research nosology for HIV-associated neurocognitive disorders, Neurology, 69 (2007), 1789-1799.
- W. R. Tyor, H. Bimonte-Nelson, A mouse model of HIV-associated neurocognitive disorders: A brain-behavior approach to discover disease mechanisms and novel treatments, J Neurovirol, 24 (2018), 180-184.
- P. M. Maki, M. H. Cohen, K. Weber, Impairments in memory and hippocampal function in HIV-positive vs HIV-negative women: A preliminary study, Neurol, 72 (2009), 1661-1668.
- S. E. Mennenga, J. E. Gerson, T. Dunckley, H. A. Bimonte-Nelson, Harmine treatment enhances short-term memory in old rats: Dissociation of cognition and the ability to perform the procedural requirements of maze testing, Physiol Behav, 138 (2015), 260-265.
- A. Ennaceur, J. Delacour, A new one-trial test for neurobiological studies of memory in rats, Behav Brain Res, 31 (1988), 47-59.