Shilpa Buch

University of Nebraska Medical Center, Omaha, Nebraska, United States

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Publications (102)449.95 Total impact

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    ABSTRACT: Although it has been documented that methamphetamine induces astrocyte activation, the mechanism(s) underlying this effect remain poorly understood. We thus sought to examine the molecular mechanisms involved in methamphetamine-mediated activation of astrocytes with a focus on the role of sigma-1 receptor (σ-1R) in this process. The expression of σ-1R and glial fibrillary acidic protein (GFAP) was examined by reverse transcription PCR (RT-PCR), real-time PCR, Western blot, and immunofluorescent staining; phosphorylation of cell signaling pathways was detected by Western blot analysis. Immunoprecipitation was used to determine the interaction between σ-1R and p-Src. Chromatin immunoprecipitation (ChIP) assay was employed to discern the binding of cAMP-response element-binding protein (CREB) with the promoter of σ-1R. The role of σ-1R in astrocyte activation was further validated in σ-1R knockout (KO) mice by Western blot combined with immunofluorescent staining. Exposure of primary rat astrocytes to methamphetamine increased the expression of σ-1R via the activation of Src, ERK mitogen-activated protein kinase, and downstream CREB pathways. Subsequently, CREB translocated into nucleus and interacted with the promoter of σ-1R resulting in increased expression of σ-1R with a concomitant increase in expression of GFAP. This effect was inhibited in cells treated with the σ-1R antagonist-BD1047, thereby implicating the role of σ-1R in the activation of astrocytes. In vivo relevance of these findings was further corroborated in σ-1R KO mice that were administered methamphetamine. In the methamphetamine administered mice, there was a failure of the drug to induce activation of astrocytes, an effect that was evident in wild-type (WT) mice exposed to methamphetamine. The study presented herein demonstrates that methamphetamine-mediated activation of astrocytes involved up-regulation of σ-1R through a positive-feedback mechanism. Understanding the regulation of σ-1R expression could provide insights into the development of potential therapeutic strategies for astrocyte activation induced by methamphetamine.
    Journal of Neuroinflammation 12/2015; 12(1). DOI:10.1186/s12974-015-0250-7 · 4.90 Impact Factor
  • PLoS ONE 04/2015; 10(4):e0124362. DOI:10.1371/journal.pone.0124362 · 3.53 Impact Factor
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    ABSTRACT: Cocaine abuse has been shown to accelerate the progression of human immunodeficiency virus (HIV)-1-associated neurological disorders (HANDs) partially through increasing neuroinflammatory response mediated by activated astrocytes; however, the detailed molecular mechanism of cocaine-mediated astrocyte activation is unclear. In the current study, we demonstrated increased astrogliosis in the cortical regions of brains from HIV(+) cocaine abusers compared with the HIV(+) group without cocaine abuse. We next sought to explore whether cocaine exposure could result in increased expression of glial fibrillary acidic protein (GFAP), a filament protein critical for astrocyte activation. Exposure of cocaine to astrocytes resulted in rapid translocation of sigma receptor to the plasma membrane with subsequent activation of downstream signaling pathways. Using a pharmacological approach, we provide evidence that cocaine-mediated upregulation of GFAP expression involved activation of mitogen-activated protein kinase (MAPK) signaling with subsequent downstream activation of the early growth response gene 1 (Egr-1). Egr-1 activation, in turn, caused transcriptional regulation of GFAP. Corroboration of these findings in vivo demonstrated increased expression of GFAP in the cortical region of mice treated with cocaine compared with the saline injected controls. A thorough understanding of how cocaine mediates astrogliosis could have implications for the development of therapeutic interventions aimed at HIV-infected cocaine abusers.
    Molecular Neurobiology 01/2015; DOI:10.1007/s12035-015-9094-5 · 5.29 Impact Factor
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    Fang Niu, honghong yao, ke liao, shilpa Buch
  • Rong Ma, Lu Yang, Fang Niu, Shilpa Buch
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    ABSTRACT: Endoplasmic reticulum (ER) stress triggered under hyperglycemic, hypoxic, and oxidative conditions has been implicated in cellular dysfunction through activation of the unfolded protein response (UPR). Recent clinical studies have documented that the release of soluble cellular and host factors following HIV infection in the central nervous system (CNS) results in induction of the ER stress response. Herein, we demonstrate that exposure of human brain microvascular endothelial cells (HBMECs) to HIV transactivator protein Tat101 resulted in early induction of several major ER stress regulators including ER chaperones Bip/GRP78 and ER stress sensors ATF6, p-PERK, and downstream mediators p-eIF2α and ATF4. Upregulation of the ER stress mediators was accompanied by decreased cell viability and increased apoptosis as evidenced by MTT and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, respectively. Pretreatment of HBMECs with either ER inhibitor or knockdown of the effector C/EBP homologous protein (CHOP) resulted in increased cell viability and abrogation of apoptosis following Tat exposure. Notably, Tat-mediated activation of the UPR response involved reactive oxygen species. Furthermore, treatment of Tat also resulted in mitochondrial dysfunction, evidenced by decrease in Bcl2/Bax ratio, dysfunction of mitochondrial membrane potential, and release of cytochrome c, all of which could be partially reversed by the ER stress inhibitor. The current study demonstrates that exposure of HBMECs to Tat induces multiple stress responses, including ER stress and mitochondrial dysfunction which in turn lead to apoptosis.
    Molecular Neurobiology 11/2014; DOI:10.1007/s12035-014-8991-3 · 5.29 Impact Factor
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    ABSTRACT: In the era of antiretroviral therapy, although the human immunodeficiency virus (HIV) replication can be successfully controlled, complications of the CNS continue to affect infected individuals. Viral Tat protein is not only neurotoxic but has also been shown to disrupt the integrity of the blood-brain barrier (BBB). Although the role of brain microvascular endothelial cells and astrocytes in Tat-mediated impairment has been well documented, pericytes, which are important constituents of the BBB and play a key role in maintaining the integrity of the barrier, remain poorly studied in the context of HIV-associated neurocognitive disorders (HAND). In the present study, we demonstrated that exposure of human brain microvascular pericytes and C3H/10T1/2 cells to HIV-1 Tat101 resulted in increased expression of platelet-derived growth factor subunit B homodimer (PDGF-BB) and increased migration of the treated cells. Furthermore, we also demonstrated that this effect of Tat was mediated via activation of mitogen-activated protein kinases and nuclear factor-κB pathways. Secreted PDGF-BB resulted in autocrine activation of the PDGF-BB/PDGF β receptor signaling pathway, culminating ultimately into increased pericyte migration. Ex vivo relevance of these findings was further corroborated in isolated microvessels of HIV Tg26 mice that demonstrated significantly increased expression of PDGF-BB in isolated brain microvessels with a concomitant loss of pericytes. Intriguingly, loss of pericyte coverage was also detected in sections of frontal cortex from humans with HIV-encephalitis compared with the uninfected controls. These findings thus implicate a novel role of PDGF-BB in the migration of pericytes, resulting in loss of pericyte coverage from the endothelium with a subsequent breach of the BBB.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 08/2014; 34(35):11812-25. DOI:10.1523/JNEUROSCI.1139-14.2014 · 6.75 Impact Factor
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    ABSTRACT: Microglia participate in innate inflammatory responses within the central nervous system. The highly conserved microRNA-9 (miR-9) plays critical roles in neurogenesis as well as axonal extension. Its role in microglial inflammatory responses, however, remains poorly understood. Here we identify a unique role of miR-9 in mediating the microglial inflammatory response via distinct signalling pathways. MiR-9-mediated regulation of cellular activation involved downregulated expression of the target protein, monocyte chemotactic protein-induced protein 1 (MCPIP1) that is crucial for controlling inflammation. Results indicate that miR-9-mediated cellular activation involved signalling via the NF-κB pathway, but not the β-catenin pathway.
    Nature Communications 07/2014; 5:4386. DOI:10.1038/ncomms5386 · 10.74 Impact Factor
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    ABSTRACT: Neuroinflammation plays critical roles in multiple sclerosis (MS). In addition to the part played by the lymphocytes, the underlying mechanisms could, in part, be also attributed to activation mediated by astrocytes. Macrophage inflammatory protein-1α (MIP-1α) has been implicated in a number of pathological conditions, specifically attributable to its potent chemottractant effects. Its modulation by IL-17, however, has received very little attention. In the present study, we demonstrated IL-17-mediated induction of MIP-1α in rat primary astroctyes through its binding to the cognate IL-17RA. Furthermore, this effect was mediated via the activation of Src, mitogen-activated protein kinases (MAPKs), PI3K/Akt and NF-kB pathways, culminating ultimately into increased expression of MIP-1α. Exposure of primary mouse astrocytes to IL-17 resulted in increased expression of glial fibrillary acidic protein and, this effect was abrogated in cells cultured in presence of the MIP-1α neutralizing antibody, thus underscoring its role in the activation of astrocytes. In vivo relevance of these findings was further corroborated in experimental autoimmune encephalomyelitis mice that demonstrated significantly increased activation of astrocytes with concomitant increased expression of MIP-1α in the corpus callosum compared with control group. Understanding the regulation of MIP-1α expression may provide insights into the development of potential therapeutic targets for neuroinflammation associated with multiple sclerosis.
    Journal of Neuroimmune Pharmacology 07/2014; 9(5). DOI:10.1007/s11481-014-9553-1 · 3.17 Impact Factor
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    ABSTRACT: Microglia are critical for the pathogenesis of HIV-associated dementia not only by acting as conduits of viral entry but also as reservoirs for productive and latent virus infection, and as producers of neurotoxins. Interaction between CX3CL1 (fractalkine) and FKN receptor (CX3CR1) is highly functional in the brain, and is known to regulate a complex network of paracrine and autocrine interactions between neurons and microglia. The aim of the present study was to determine what extent HIV-1 Tat protein causes the alteration of CX3CR1 expression and to investigate the regulatory mechanism for CX3CR1 expression. Here we showed that exposure of primary microglia and BV2 cells to exogenous Tat protein resulted in down-regulation of CX3CR1 mRNA and protein expression, with a concomitant induction of proinflammatory responses. Next, we further showed that NF-κB activation by Tat treatment negatively regulated CX3CR1 expression. Since a YY1 binding site ~10kb upstream of CX3CR1 promoter was predicted in rats, mice and humans, the classical NF-κB-YY1 regulatory pathway was considered. Our findings indicated that Tat repressed CX3CR1 expression via NF-κB-YY1 regulatory pathway. To gain insight into the effect of Tat on CX3CL1-CX3CR1 communication, calcium mobilization, MAPK activation and microglial migration, respectively, were tested in microglial cells after successive treatment with Tat and CX3CL1. The results suggested that Tat disrupted the responses of microglia to CX3CL1. Taken together, these results demonstrate that HIV-1 Tat protein suppresses CX3CR1 expression in microglia via NF-κB-YY1 pathway and attenuates CX3CL1-induced functional response of microglia.
    Current HIV Research 05/2014; 12(3). DOI:10.2174/1570162X12666140526123119 · 2.14 Impact Factor
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    ABSTRACT: On May 23, 2013 scientific leaders in the neuroAIDS community met at the University of Nebraska Medical Center to discuss cellular interaction and signaling for the third annual human immunodeficiency virus and neuroAIDS colloquium. The meeting continues a series of contemporary scientific issues related to how virus effects the nervous system. In 2011 the focus was on animal models and in 2012 in biomarkers. Here, our 2013 meeting featured ten presentations from outstanding scientists examining how inter- and intra-cellular processes contribute to neuropathogenesis. Talks highlighted emerging issues, findings, and potential therapies, followed by a panel discussion in which controversies in the field and gaps in our current knowledge were identified. The panel discussion was transcribed into the article and published as a field perspective. A link is available where all of the presentations and the concluding discussion can be seen and heard. The third annual University of Nebraska Medical Center (UNMC) colloquium on current issues in neuroAIDS was held on May 23, 2013. Following the presentations, which can be viewed at http://www.unmc.edu/pharmacology/CISN.htm . A panel discussion ensued. This discussion raised important topical issues. To disseminate this information, a transcript is provided below.
    Journal of Neuroimmune Pharmacology 05/2014; DOI:10.1007/s11481-014-9545-1 · 3.17 Impact Factor
  • Shilpa Buch
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    ABSTRACT: Cells possess complex growth factor networks that play vital roles in regulating fundamental life processes. Such protein factors exert their action by binding to cognate cell specific receptors resulting in regulation of cell division, differentiation, chemotaxis or apoptosis. Engagement of receptors by their respective ligands results in activation of sequential protein phosphorylation cascades, culminating downstream into activation of gene transcription. These factors are expressed ubiquitously under a variety of conditions by normal as well as transformed cells, thereby underpinning their function in autocrine and paracrine stimulation of cells under several physiological and pathological conditions. Despite major advances in our understanding of growth factors, their paradoxical roles in normal cellular homeostasis and pathologies underpin the need to examine their roles in disease and health. The goal of this special issue is to present emerging trends in the roles that growth factors play in inflammatory disease processes that include cardiovascular, cancer, stroke and neurodegenerative processes associated with aging, viral infection and substance abuse with the ultimate aim to pave the way for future therapeutic breakthroughs.
    Journal of Neuroimmune Pharmacology 03/2014; 9(2). DOI:10.1007/s11481-014-9534-4 · 3.17 Impact Factor
  • Shilpa Buch
    Journal of the neurological sciences 02/2014; DOI:10.1016/j.jns.2014.01.043 · 2.26 Impact Factor
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    ABSTRACT: HIV-1 associated dementia remains a significant public health burden. Clinical and experimental research has shown that reduced levels of brain-derived neurotrophic factor (BDNF) may be a risk factor for neurological complications associated with HIV-1 infection. We are actively testing genetically modified macrophages for their possible use as the cell-based gene delivery vehicle for the central nervous system (CNS). It can be an advantage to use the natural homing/migratory properties of monocyte-derived macrophages to deliver potentially neuroprotective BDNF into the CNS, as a non-invasive manner. Lentiviral-mediated gene transfer of human (h)BDNF plasmid was constructed and characterized. Defective lentiviral stocks were generated by transient transfection of 293T cells with lentiviral transfer plasmid together with packaging and envelope plasmids. High titer lentiviral vector stocks were harvested and used to transduce human neuronal cell lines, primary cultures of human peripheral mononocyte-derived macrophages (hMDM) and murine myeloid monocyte-derived macrophages (mMDM). These transduced cells were tested for hBDNF expression, stability, and neuroprotective activity. The GenomeLab GeXP Genetic Analysis System was used to evaluate transduced cells for any adverse effects by assessing gene profiles of 24 reference genes. High titer vectors were prepared for efficient transduction of neuronal cell lines, hMDM, and mMDM. Stable secretion of high levels of hBDNF was detected in supernatants of transduced cells using western blot and ELISA. The conditioned media containing hBDNF were shown to be protective to neuronal and monocytic cell lines from TNF-α and HIV-1 Tat mediated cytotoxicity. Lentiviral vector-mediated gene transduction of hMDM and mMDM resulted in high-level, stable expression of the neuroprotective factorBDNF in vitro. These findings form the basis for future research on the potential use of BDNF as a novel therapy for neuroAIDS.
    PLoS ONE 02/2014; 9(2):e82030. DOI:10.1371/journal.pone.0082030 · 3.53 Impact Factor
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    L Yang, J Chao, Y H Kook, Y Gao, H Yao, S J Buch
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    ABSTRACT: Highly conserved microRNA-9 (miR-9) has a critical role in various cellular processes including neurogenesis. However, its regulation by neurotropins that are known to mediate neurogenesis remains poorly defined. In this study, we identify platelet-derived growth factor-BB (PDGF-BB)-mediated upregulation of miR-9, which in turn downregulates its target gene monocyte chemotactic protein-induced protein 1 (MCPIP1), as a key player in modulating proliferation, neuronal differentiation as well as migration of neuronal progenitor cells (NPCs). Results indicate that miR-9-mediated NPC proliferation and neuronal differentiation involves signaling via the nuclear factor-kappa B (NF-κB) and cAMP response element-binding protein (CREB) pathways, and that NPC migration involves CREB but not the NF-κB signaling. These findings thus suggest that miR-9-mediated downregulation of MCPIP1 acts as a molecular switch regulation of neurogenesis.
    Cell Death & Disease 12/2013; 4:e960. DOI:10.1038/cddis.2013.486 · 5.18 Impact Factor
  • Jie Chao, Lu Yang, Honghong Yao, Shilpa Buch
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    ABSTRACT: Our previous study demonstrated that platelet-derived growth factor-BB (PDGF-BB) increased the cell proliferation of primary rat neuronal progenitor cells (NPCs). However, whether PDGF-BB regulates neurogenesis in HIV-associated neurological disorder (HAND) remains largely unknown. In this study we demonstrated that pre-treatment of NPCs with PDGF-BB restored Tat-mediated impairment of cell proliferation via activation of p38 and JNK MAPK pathways. Moreover, treatment with PDGF-BB induced inactivation of glycogen synthase kinase-3β (GSK-3β), evidenced by its phosphorylation at Ser9, this effect was significantly inhibited by the p38 and JNK inhibitors. Level of nuclear β-catenin, the primary substrate of GSK-3β, was also concomitantly increased following PDGF-BB treatment, suggesting that PDGF-BB stimulates NPC proliferation via acting on GSK-3β to promote nuclear accumulation of β-catenin. This was further validated by gain and loss of function studies using cells transfected with either the wild type or mutant GSK-3β constructs. Together these data underpin the role of GSK-3β/β-catenin as a novel target that regulates NPC proliferation mediated by PDGF-BB with implications for therapeutic intervention for reversal of impaired neurogenesis inflicted by Tat.
    Journal of Neuroimmune Pharmacology 11/2013; 9(2). DOI:10.1007/s11481-013-9509-x · 3.17 Impact Factor
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    Dennis Kolson, Shilpa Buch
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    ABSTRACT: Developing a validated tool for the rapid and efficient assessment of cognitive functioning in HIV-infected patients in a typical outpatient clinical setting has been an unmet goal of HIV research since the recognition of the syndrome of HIV-associated dementia (HAD) nearly 20 years ago. In this issue of JNIP Cross et al. report the application of the International HIV Dementia Scale (IHDS) in a U.S.-based urban outpatient clinic to evaluate its utility as a substitute for the more time- and effort-demanding formalized testing criteria known as the Frascati criteria that was developed in 2007 to define the syndrome of HIV-associated neurocognitive disorders (HAND). In this study an unselected cohort of 507 individuals (68 % African American) that were assessed using the IHDS in a cross-sectional study revealed a 41 % prevalence of cognitive impairment (labeled 'symptomatic HAND') that was associated with African American race, older age, unemployment, education level, and depression. While the associations between cognitive impairment and older age, education, unemployment status and depression in HIV-infected patients are not surprising, the association with African American ancestry and cognitive impairment in the setting of HIV infection is a novel finding of this study. This commentary discusses several important issues raised by the study, including the pitfalls of assessing cognitive functioning with rapid screening tools, cognitive testing criteria, normative testing control groups, accounting for HAND co-morbidity factors, considerations for clinical trials assessing HAND, and selective population vulnerability to HAND.
    Journal of Neuroimmune Pharmacology 11/2013; 8(5). DOI:10.1007/s11481-013-9513-1 · 3.17 Impact Factor
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    ABSTRACT: Lung diseases such as chronic obstructive pulmonary disease (COPD), asthma, and lung infections are major causes of morbidity and mortality among HIV-infected patients even in the era of antiretroviral therapy (ART). Many of these diseases are strongly associated with smoking and smoking is more common among HIV-infected than uninfected people; however, HIV is an independent risk factor for chronic bronchitis, COPD, and asthma. The mechanism by which HIV promotes these diseases is unclear. Excessive airway mucus formation is a characteristic of these diseases and contributes to airway obstruction and lung infections. HIV gp120 plays a critical role in several HIV-related pathologies and we investigated whether HIV gp120 promoted airway mucus formation in normal human bronchial epithelial (NHBE) cells. We found that NHBE cells expressed the HIV-coreceptor CXCR4 but not CCR5 and produced mucus in response to CXCR4-tropic gp120. The gp120-induced mucus formation was blocked by the inhibitors of CXCR4, α7-nicotinic acetylcholine receptor (α7-nAChR), and γ-aminobutyric acid (GABA)AR but not the antagonists of CCR5 and epithelial growth factor receptor (EGFR). These results identify two distinct pathways (α7-nAChR-GABAAR and EGFR) for airway mucus formation and demonstrate for the first time that HIV-gp120 induces and regulates mucus formation in the airway epithelial cells through the CXCR4-α7-nAChR-GABAAR pathway. Interestingly, lung sections from HIV ± ART and simian immunodeficiency virus (SIV) ± ART have significantly more mucus and gp120-immunoreactivity than control lung sections from humans and macaques, respectively. Thus, even after ART, lungs from HIV-infected patients contain significant amounts of gp120 and mucus that may contribute to the higher incidence of obstructive pulmonary diseases in this population.
    PLoS ONE 10/2013; 8(10):e77160. DOI:10.1371/journal.pone.0077160 · 3.53 Impact Factor
  • Shilpa J Buch
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    ABSTRACT: This Commenatry highlights the article by Rom et al which shows that selective cannabinoid receptor 2 activation in leukocytes decreases key steps in monocyte-blood brain barrier engagement suppressing inflammatory leukocyte responses and preventing neuroinflammation.
    American Journal Of Pathology 09/2013; DOI:10.1016/j.ajpath.2013.08.003 · 4.60 Impact Factor
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    ABSTRACT: Recruitment of immune cells such as monocytes/macrophages and dendritic cells (DCs) across the blood-brain barrier (BBB) has been documented in diseases involving neuroinflammation. Neuroinvasion by HIV leads to neurocognitive diseases and alters the permeability of the BBB. Likewise, many HIV patients use drugs of abuse such as morphine, which can further compromise the BBB. While the role of monocytes and macrophages in neuroAIDS is well established, research demonstrating the presence and role of DCs in the CNS during HIV infection has not been developed yet. In this respect, this study explored the presence of DCs in the brain parenchyma of rhesus macaques infected with a neurovirulent form of SIV (SIV mac239 R71/17E) and administered with morphine. Cells positive for DC markers including CD11c (integrin), macDC-SIGN (dendritic cell-specific ICAM-3 grabbing nonintegrin), CD83 (a maturation factor), and HLA-DR (MHC class II) were consistently found in the brain parenchyma of SIV-infected macaques as well as infected macaques on morphine. Control animals did not exhibit any DC presence in their brains. These results provide first evidence of DCs' relevance in NeuroAIDS vis-à-vis drugs of abuse and open new avenues of understanding and investigative HIV-CNS inflictions.
    Journal of NeuroVirology 08/2013; 19(5). DOI:10.1007/s13365-013-0182-x · 3.32 Impact Factor
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    ABSTRACT: The control and eradication of neurological complications associated with AIDS continues to be an important goal in efforts toward improving the well being of HIV-infected patients. Although combined antiretroviral therapies have contributed significantly to increasing the longevity of patients by suppressing the virus burden in the systemic compartments, the prevalence of HIV-associated neurological disorders continues to be on the rise. This in turn, leads to an impaired quality of life of the infected individuals who continue to suffer from mild to moderate cognitive decline and memory loss. Developing therapeutic interventions that reverse neuronal injury in the context of HIV infection, is thus of paramount importance in the field. Our previous studies have demonstrated that platelet-derived growth factor (PDGF) has a neuroprotective potential against HIV envelope protein gp120 and Tat. Paradoxically, PDGF is also a cerebrovascular permeant with deleterious effects on the blood-brain barrier resulting in increased influx of monocytes in the CNS. Herein, we review the opposing roles of PDGF in the context of HIV-associated neurodegenerative disorder (HAND).
    Journal of Neuroimmune Pharmacology 06/2013; DOI:10.1007/s11481-013-9481-5 · 3.17 Impact Factor

Publication Stats

2k Citations
449.95 Total Impact Points

Institutions

  • 2009–2015
    • University of Nebraska Medical Center
      • Department of Pharmacology and Experimental Neuroscience
      Omaha, Nebraska, United States
    • Ponce School of Medicine and Health Sciences
      • Department of Microbiology
      Ponce, Ponce Municipio, Puerto Rico
  • 2011–2014
    • University of Nebraska at Omaha
      • Department of Pharmacology and Experimental Neuroscience
      Omaha, Nebraska, United States
  • 2009–2014
    • The Nebraska Medical Center
      Omaha, Nebraska, United States
  • 2007–2009
    • University of Kansas
      • Department of Molecular and Integrative Physiology
      Lawrence, Kansas, United States
  • 2000–2009
    • Kansas City VA Medical Center
      Kansas City, Missouri, United States
  • 2005–2006
    • Emory University
      • Department of Pathology and Laboratory Medicine
      Atlanta, Georgia, United States
  • 2004
    • Johns Hopkins University
      • Department of Neurology
      Baltimore, Maryland, United States