Kimberly B Bjugstad, William D Flitter, Gary W Arendash
{"title":"Intracerebroventricular infusions of gp120 inhibit weight gain and induce atrophy in the hippocampus and neostriatum without affecting cognition.","authors":"Kimberly B Bjugstad, William D Flitter, Gary W Arendash","doi":"10.1300/J128v02n04_02","DOIUrl":"https://doi.org/10.1300/J128v02n04_02","url":null,"abstract":"<p><p>The HIV envelope protein, gp120, has been proposed to be a key agent in the development of AIDS dementia complex (ADC). To elucidate CNS effects that gp120 alone may be inducing in ADC, the present study investigated changes in weight, motor activity, cognitive function and corresponding neuropathology in rats given daily bilateral infusions of gp120 intracerebroventricularly for 7 days. gp120 inhibited weight gain, but had no measurable effects on motor activity or water maze cognitive performance. Nonetheless, gp120 infusions did induce both hippocampal and neostriatal atrophy. Thus, gp120 alone can cause ADC-related neuropathologic and weight changes, but gp120 alone was not sufficient to induce impairments in spatial learning and memory.</p>","PeriodicalId":73854,"journal":{"name":"Journal of neuro-AIDS","volume":"2 4","pages":"15-31"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1300/J128v02n04_02","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26167616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M D Johnson, P Kim, W Tourtellotte, C F Federspiel
{"title":"Transforming growth factor beta and monocyte chemotactic protein-1 are elevated in cerebrospinal fluid of immunocompromised patients with HIV-1 infection.","authors":"M D Johnson, P Kim, W Tourtellotte, C F Federspiel","doi":"10.1300/J128v02n04_03","DOIUrl":"https://doi.org/10.1300/J128v02n04_03","url":null,"abstract":"<p><p>Monocyte infiltration of the brain is central to the pathogenesis of HIV-1 encephalitis. The cytokines promoting recruitment of monocytes into the central nervous system during HIV-1 infection are not established. In this study, we evaluated human cerebrospinal fluid from patients with HIV-1 infection for transforming growth factor beta1 (TGFbeta1) and monocyte chemotactic protein-1 (MCP-1) using a quantitative sandwich enzyme-linked immunoassays. Cytokine levels were compared to those from patients with multiple sclerosis and normal controls. In cerebrospinal fluid of patients with HIV-1 infection and CD4<500 cells/mm3, both TGFbeta1 and MCP-1 were significantly elevated compared to those with CD4>500 cells/mm3, multiple sclerosis, and controls.</p>","PeriodicalId":73854,"journal":{"name":"Journal of neuro-AIDS","volume":"2 4","pages":"33-43"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1300/J128v02n04_03","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26167617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Robert K Fujimura, Imad Khamis, Paul Shapshak, Karl Goodkin
{"title":"Regional quantitative comparison of multispliced to unspliced ratios of HIV-1 RNA copy number in infected human brain.","authors":"Robert K Fujimura, Imad Khamis, Paul Shapshak, Karl Goodkin","doi":"10.1300/J128v02n04_04","DOIUrl":"https://doi.org/10.1300/J128v02n04_04","url":null,"abstract":"<p><p>Infection of the brain by HIV-1 often results in cognitive- motor disorders, the most severe form being HIV-1 associated dimentia (HAD). However, the etiology and pathogenesis of neuroAIDS at the molecular level is still not fully understood and controversial issues remain, including the significance of abortive infection and localized viral load. This paper proposes that quantitative comparison of HIV-1 proviral and RNAloads across the brain will clarify some of these issues. It was hypothesized that there are differences in ratios of multispliced and unspliced HIV RNA in different regions of brain by analogy with prior findings of brain regional differences in virus and strains of HIV-1. A competitive RT-PCR method was used to compare ratios of multispliced to unspliced HIV-1 RNA's across brain regions of one case with HAD. Statistical analysis results showed that data obtained by repeated assays for each RNA preparation were not significantly different. Significant differences were detected between specimens obtained from different regions of the brain. The ratio of MS/US RNA in the frontal lobe was significantly greater than in the basal ganglia, medial temporal lobe, and another site in the temporal lobe. It must be noted that our approach has been the analysis of macroscopic brain regions separated by several centimeters; future studies will analyze microscopic analysis of these brain regions. The current study was preformed to produce results on gross differences in neuroanatomical locations at cm distances. Future studies will be performed to compare different regions with microscopic anatomic specificity.</p>","PeriodicalId":73854,"journal":{"name":"Journal of neuro-AIDS","volume":"2 4","pages":"45-60"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1300/J128v02n04_04","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26167618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J K Johnson, K A Warren, N E J Berman, O Narayan, E B Stephens, S V Joag, R Raghavan, J K Marcario, P D Cheney
{"title":"Manifestations of SIV-induced ocular pathology in macaque monkeys.","authors":"J K Johnson, K A Warren, N E J Berman, O Narayan, E B Stephens, S V Joag, R Raghavan, J K Marcario, P D Cheney","doi":"10.1300/J128v02n04_01","DOIUrl":"https://doi.org/10.1300/J128v02n04_01","url":null,"abstract":"<p><p>Simian immunodeficiency virus has been shown to cause acquired immunodeficiency syndrome in macaque monkeys. Data gathered from clinical examination and fundus photography have shown that the lentivirus is capable of the induction of choroidal lesions and retinal hemorrhages in the macaque. These findings demonstrate the potential value of the macaque monkey eye as a model of the retinal pathology routinely seen in human AIDS patients.</p>","PeriodicalId":73854,"journal":{"name":"Journal of neuro-AIDS","volume":"2 4","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1300/J128v02n04_01","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26167615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fred Ingram, Leena Ketonen, David Paar, Eric Avery
{"title":"Memory implications of a \"fornix white line\" in HIV infection.","authors":"Fred Ingram, Leena Ketonen, David Paar, Eric Avery","doi":"10.1300/j128v02n03_06","DOIUrl":"https://doi.org/10.1300/j128v02n03_06","url":null,"abstract":"<p><p>The \"fornix white line\" (FWL) is a brain abnormality detected on magnetic resonance imaging (MRI) in some people with human immunodeficiency virus (HIV) infection. This finding has previously been associated with clinical findings of cognitive disturbance, particularly regarding memory. The current study provides preliminary substantiation of the previously reported clinical finding of FWL-associated memory disturbance through formal psychometric evaluation over time. Specifically, despite comparable baseline performances, 8-10 months later subjects without the FWL improved performance on neuropsychological verbal memory testing, while subjects with the FWL declined; the magnitude of this dissociation on follow-up was 1.5 to 2.2 standard deviations. In contrast, general cognitive status, as assessed through performance on the Mini-Mental State Exam, remained comparable between groups and stable over time. Further, the comparable CD4 count and Karnofsky scores at baseline counters the argument that the FWL is simply a marker of HIV disease progression. These preliminary findings suggest the need for future research of the hypotheses raised thereby; particularly salient is the hypothesis that the FWL may serve as an earlier marker indicating anti-CMV treatment before memory impairment is clinically apparent.</p>","PeriodicalId":73854,"journal":{"name":"Journal of neuro-AIDS","volume":"2 3","pages":"83-90"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1300/j128v02n03_06","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26167614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rodrigo O Kuljis, Paul Shapshak, Philip Alcabes, Pura Rodríguez de la Vega, Robert Fujimura, Carol K Petito
{"title":"Increased density of neurons containing NADPH diaphorase and nitric oxide synthase in the cerebral cortex of patients with HIV-1 infection and drug abuse.","authors":"Rodrigo O Kuljis, Paul Shapshak, Philip Alcabes, Pura Rodríguez de la Vega, Robert Fujimura, Carol K Petito","doi":"10.1300/j128v02n03_02","DOIUrl":"https://doi.org/10.1300/j128v02n03_02","url":null,"abstract":"<p><p>To determine whether nitrogen monoxide (nitric oxide; NO) synthase (NOS) and NADPH diaphorase (NDP) co-containing cerebrocortical neurons (NOSN) neurons are affected in patients infected with human immunodeficiency virus type 1 (HIV-1) with and without associated intake of drugs of abuse, we examined the temporal neocortex of 24 individuals: 12 HIV-1 positive (including 3 drug users, 9 non-drug users) and 12 HIV-1 negative (including 6 drug users, and 6 non-drug users). Histochemical labeling for NDP-an enzymatic domain co-expressed in the NOS enzyme-was employed to visualize NOSN. Drug abuse and HIV-1 infection cause independently an increase in NOSN density, but combined they result in up to a 38-fold increase in NOSN density, suggesting that the combination of these factors induces NOS expression powerfully in neurons that normally do not synthesize NDP/NOS. This is associated with an increase in the proportion of NOSN displaying dystrophic changes, indicating that NOSN undergo massive degeneration in association with NOS synthesis induction. The increase in density of NOSN in HIV-1 infected drug abusers may be among the important sources of NO mediating cerebrocortical dysfunction, and the degeneration of NOS-containing local circuit neurons in patients with HIV-1 infection or drug abuse may underlie in part their neuropsychiatric manifestations.</p>","PeriodicalId":73854,"journal":{"name":"Journal of neuro-AIDS","volume":"2 3","pages":"19-36"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26168182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lynn Nielsen-Bohlman, George Fein, Devon Boyle, Frank Ezekiel
{"title":"N400 event-related potential reduction indexes: early central nervous system impairment in HIV.","authors":"Lynn Nielsen-Bohlman, George Fein, Devon Boyle, Frank Ezekiel","doi":"10.1300/j128v02n03_04","DOIUrl":"https://doi.org/10.1300/j128v02n03_04","url":null,"abstract":"<p><p>We examined event-related potential (ERP) measures of priming in a lexical decision task in which two-thirds of the words were presented as sequential antonym pairs. HIV-1+ subjects were divided into cognitively normal and cognitively impaired subgroups on the basis of a neuropsychological battery. Cognitively impaired HIV-1+ subjects showed reduced priming, associated with reduced N400 ERP component amplitudes, suggesting that the processing of linguistic stimuli in these patients may involve reduced activation of semantic networks. Cognitively normal HIV-1+ subjects showed a reduction in N400 amplitude, but no reduction in performance, suggesting that some reduction in neural signal may occur earlier in the course of HIV-1 central nervous system disease than behavioral priming deficit. As the known neurological deficit in HIV-1 disease is primarily in the basal ganglia and periventricular white matter, we propose that a functional disconnection of subcortical and frontal structures from posterior cortical structures underlies this reduction in semantic activation.</p>","PeriodicalId":73854,"journal":{"name":"Journal of neuro-AIDS","volume":"2 3","pages":"51-65"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26168183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evolution of neuro-AIDS during the HAART era.","authors":"Karl Goodkin","doi":"10.1300/j128v02n03_01","DOIUrl":"https://doi.org/10.1300/j128v02n03_01","url":null,"abstract":"","PeriodicalId":73854,"journal":{"name":"Journal of neuro-AIDS","volume":"2 3","pages":"1-17"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1300/j128v02n03_01","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26168181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paul Shapshak, Renée V Stewart, Pura Rodriguez de la Vega, Boanerges Dominguez, Robert Fujimura, David M Segal, Nora C J Sun, Silvia Delgado, Carol Petito
{"title":"Brain macrophage surface marker expression with HIV-1 infection and drug abuse: a preliminary study.","authors":"Paul Shapshak, Renée V Stewart, Pura Rodriguez de la Vega, Boanerges Dominguez, Robert Fujimura, David M Segal, Nora C J Sun, Silvia Delgado, Carol Petito","doi":"10.1300/j128v02n03_03","DOIUrl":"https://doi.org/10.1300/j128v02n03_03","url":null,"abstract":"<p><strong>Goal: </strong>To determine the heterogeneity of surface marker expression of macrophages in the temporal lobe of patients who died with AIDS who were also Drug Abusers (DAs). We studied the expression of macrophage surface markers CD11c, CD14, CD68, and HLA-DR and T cell surface markers CD4, and CD8.</p><p><strong>Background: </strong>The macrophage is the prime locus for HIV-1-associated pathology, is the most frequently infected cell in the brain, and has the highest virus load compared to other cells. We previously described the heterogeneity of macrophage surface marker expression and performed morphometric analysis in peripheral nerves of patients who died from AIDS compared to HIV-1 negative individuals. We showed that the HIV-related neuropathy in AIDS is a multifocal process. It is similarly important to determine the expression of macrophage surface markers in brain. Temporal lobe tissue was selected for this preliminary study because we previously found elevated HIV-1 proviral DNA load and inflammatory processes in this neuroanatomic location for subjects who died with AIDS. There is a high prevalence of Drug Abuse in Miami, Florida, associated with AIDS that may interactively affect HIV-associated pathology.</p><p><strong>Methods: </strong>Temporal lobe tissue was examined from 17 HIV-1-seropositive patients (4 with Drug Abuse and 13 without Drug Abuse) and 11 HIV-seronegative individuals (5 with Drug Abuse and 6 without Drug Abuse). Standard immunohistochemistry utilized alkaline phosphatase conjugate secondary antibody and fuchsin substrate.</p><p><strong>Results: </strong>We found that HIV-1 infection and the interaction of HIV-1 infection and Drug Abuse produced changes in macrophage surface marker expression. Macrophage surface markers, CD11c, CD14, CD68, and HLA-DR, and T-cell marker CD4 were increased with statistical significance due to HIV-1 infection (all p < .001) whereas CD8 remained unchanged. Changes due to Drug Abuse alone were not significant. Interaction of Drug Abuse and HIV-infected individuals showed increased expression of CD68 (p = .011), HLA-DR (p = .001), CD4 (p = .027), and CD8 (p = .016).</p><p><strong>Conclusion: </strong>Drug Abuse and HIV-1 infection are factors that differentially and interactively result in multiple macrophages surface marker effects. In HIV-1 infected individuals, Drug Abuse stimulates surface marker expression. Since brain macrophage surface makers do not change uniformly as a result of Drug Abuse and HIV infection, these cells may be heterogeneous and contain sub-types (sub-sets). It remains to be determined which macrophage sub-types may be most pathognomic for pathology.</p>","PeriodicalId":73854,"journal":{"name":"Journal of neuro-AIDS","volume":"2 3","pages":"37-50"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26168184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Degenerative and inflammatory lesions in sympathetic ganglia: further morphological evidence for an autonomic neuropathy in AIDS.","authors":"L Chimelli, A R Martins","doi":"10.1300/j128v02n03_05","DOIUrl":"https://doi.org/10.1300/j128v02n03_05","url":null,"abstract":"<p><p>There is accumulating evidence that autonomic dysfunction occurs in HIV infection. While many studies have demonstrated autonomic abnormalities on clinical basis, only one has studied the morphology of sympathetic ganglia. The superior sympathetic ganglia of 12 randomly selected AIDS patients and those of 6 controls were examined morphologically in order to determine the frequency and severity of their involvement. Although they had not been investigated for autonomic dysfunction, 5 had suffered from non-infectious diarrhoea, one showed bilateral ptosis and another had non-specified visual problems. All cases showed clusters, and perivascular mononuclear inflammatory cells, occasionally infiltrating vessel walls, some evidence of nerve cell degeneration, and proliferation of capsule cells. Immunostainings showed T lymphocytes and an increased number of macrophages. HIV antigens were detected in macrophages, in 6 cases (50%). This study provides further morphological support for the autonomic dysfunction in association with HIV infection. As for the mechanism of this dysfunction, it has been postulated a direct infection, the virus entering the ganglia through macrophages and acting as a reservoir for HIV, and an autoimmune pathogenesis. Since HIV antigens were not detected in 50% of the cases in this and in a previous study, despite the existence of morphological lesions, it is possible that, as in HIV-related sensory-motor peripheral neuropathies, an autoimmune mechanism may also play a role in the development of the autonomic lesions.</p>","PeriodicalId":73854,"journal":{"name":"Journal of neuro-AIDS","volume":"2 3","pages":"67-82"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1300/j128v02n03_05","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26168185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}