Publish in OALib Journal

ISSN: 2333-9721

APC: Only $99


Any time

2018 ( 1 )

2016 ( 1 )

2015 ( 2 )

2014 ( 10 )

Custom range...

Search Results: 1 - 10 of 238 matches for " Tammy Kielian "
All listed articles are free for downloading (OA Articles)
Page 1 /238
Display every page Item
Immunopathogenesis of brain abscess
Tammy Kielian
Journal of Neuroinflammation , 2004, DOI: 10.1186/1742-2094-1-16
Abstract: Brain abscesses develop in response to a parenchymal infection with pyogenic bacteria, beginning as a localized area of cerebritis and evolving into a suppurative lesion surrounded by a well-vascularized fibrotic capsule. The leading etiologic agents of brain abscess are the streptococcal strains and S. aureus, although a myriad of other organisms have also been reported [1,2]. Brain abscess represents a significant medical problem, accounting for one in every 10,000 hospital admissions in the United States, and remains a serious situation despite recent advances made in detection and therapy [2]. In addition, the emergence of multi-drug resistant strains of bacteria has become a confounding factor. Following infection, the potential sequelae of brain abscess include the replacement of the abscessed area with a fibrotic scar, loss of brain tissue by surgical excision, or abscess rupture and death. Indeed, if not detected early, an abscess has the potential to rupture into the ventricular space, a serious complication with an 80% mortality rate [1]. The most common sources of brain abscess are direct or indirect cranial infection arising from the paranasal sinuses, middle ear, and teeth. Other routes include seeding of the brain from distant sites of infection in the body (i.e. endocarditis) or penetrating trauma to the head. Following brain abscess resolution patients may experience long-term complications including seizures, loss of mental acuity, and focal neurological defects that are lesion site-dependent.At the histological level, brain abscess is typified by a sequential series of pathological changes that have been elucidated using the experimental rodent models described in detail below [3-7]. Staging of brain abscess in humans has been based on findings obtained during CT or MRI scans. The early stage or early cerebritis occurs from days 1–3 and is typified by neutrophil accumulation, tissue necrosis, and edema. Microglial and astrocyte activation is also e
Differential effects of interleukin-17 receptor signaling on innate and adaptive immunity during central nervous system bacterial infection
Debbie Vidlak, Tammy Kielian
Journal of Neuroinflammation , 2012, DOI: 10.1186/1742-2094-9-128
Effects of low dose GM-CSF on microglial inflammatory profiles to diverse pathogen-associated molecular patterns (PAMPs)
Nilufer Esen, Tammy Kielian
Journal of Neuroinflammation , 2007, DOI: 10.1186/1742-2094-4-10
Abstract: Although the concentration of GM-CSF used in our protocol for mouse microglial expansion (0.5 ng/ml) is at least 10-fold less compared to doses reported to affect microglial maturation and function (≥ 5 ng/ml), in this study we compared the responses of microglia derived from mixed glial cultures propagated in the presence/absence of low dose GM-CSF to establish whether this growth factor significantly altered the immune properties of microglia to diverse bacterial stimuli. These stimuli included the gram-positive pathogen Staphylococcus aureus (S. aureus) and its cell wall product peptidoglycan (PGN), a Toll-like receptor 2 (TLR2) agonist; the TLR3 ligand polyinosine-polycytidylic acid (polyI:C), a synthetic mimic of viral double-stranded RNA; lipopolysaccharide (LPS) a TLR4 agonist; and the TLR9 ligand CpG oligonucleotide (CpG-ODN), a synthetic form of bacteria/viral DNA.Interestingly, the relative numbers of microglia recovered from mixed glial cultures following the initial harvest were not influenced by GM-CSF. However, following the second and third collections of the same mixed cultures, the yield of microglia from GM-CSF-supplemented flasks was increased two-fold. Despite the ability of GM-CSF to expand microglial numbers, cells propagated in the presence/absence of GM-CSF demonstrated roughly equivalent responses following S. aureus and PGN stimulation. Specifically, the induction of tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-2 (MIP-2/CXCL2), and major histocompatibility complex (MHC) class II, CD80, CD86 expression by microglia in response to S. aureus were similar regardless of whether cells had been exposed to GM-CSF during the mixed culture period. In addition, microglial phagocytosis of intact bacteria was unaffected by GM-CSF. In contrast, upon S. aureus stimulation, CD40 expression was induced more prominently in microglia expanded in GM-CSF. Analysis of microglial responses to additional pathogen-associate molecular patterns (P
MyD88 is pivotal for immune recognition of Citrobacter koseri and astrocyte activation during CNS infection?
Shuliang Liu, Tammy Kielian
Journal of Neuroinflammation , 2011, DOI: 10.1186/1742-2094-8-35
Abstract: Citrobacter koseri (formerly known as C. diversus) is a Gram-negative bacillus with a predilection for causing meningitis and multi-focal brain abscesses in human neonates [1,2]. In fact, almost one-third of infants and young children infected with C. koseri succumb to the disease, and approximately half of those who survive infection experience long-term neurological deficits due to focal or diffuse brain damage [1,2]. Increasing evidence has accumulated demonstrating that innate immune responses are tailored towards specific pathogen classes [3-5]. Specifically, the types of responses elicited by Gram-positive bacteria can differ significantly from those triggered by Gram-negative pathogens. In addition, the majority of studies examining bacterial pathogenesis in the CNS have utilized Gram-positive organisms [6-8], which eliminates the involvement of key Toll-like receptors (TLRs) that may trigger distinct pathways during Gram-negative infections (i.e. TLR4, TLR5). Therefore, it is important to investigate the CNS response to divergent pathogens to identify unique as well as conserved responses, which may facilitate the development of novel treatment strategies that would cross multiple bacterial species.The innate immune system recognizes multiple pathogen classes via highly conserved molecular motifs, termed pathogen-associated molecular patterns (PAMPs), through a limited set of germ-line encoded receptors known as pattern recognition receptors (PRRs) [9,10]. Toll-like receptors (TLRs) are a family of PRRs responsible for sensing numerous PAMPs of bacterial, viral, and fungal species [9]. For example, lipoproteins and LPS contained in the outer cell wall of Gram-negative bacteria are agonists for TLR2 and TLR4, respectively; flagellin, which is the main component of bacterial flagella, engages TLR5; and bacterial DNA containing unmethylated CpG motifs binds to TLR9. Since Citrobacter are Gram-negative bacilli and possess an outer cell wall rich in LPS, it was a
MyD88-Dependent Signaling Influences Fibrosis and Alternative Macrophage Activation during Staphylococcus aureus Biofilm Infection
Mark L. Hanke, Amanda Angle, Tammy Kielian
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0042476
Abstract: Bacterial biofilms represent a significant therapeutic challenge based on their ability to evade host immune and antibiotic-mediated clearance. Recent studies have implicated IL-1β in biofilm containment, whereas Toll-like receptors (TLRs) had no effect. This is intriguing, since both the IL-1 receptor (IL-1R) and most TLRs impinge on MyD88-dependent signaling pathways, yet the role of this key adaptor in modulating the host response to biofilm growth is unknown. Therefore, we examined the course of S. aureus catheter-associated biofilm infection in MyD88 knockout (KO) mice. MyD88 KO animals displayed significantly increased bacterial burdens on catheters and surrounding tissues during early infection, which coincided with enhanced dissemination to the heart and kidney compared to wild type (WT) mice. The expression of several proinflammatory mediators, including IL-6, IFN-γ, and CXCL1 was significantly reduced in MyD88 KO mice, primarily at the later stages of infection. Interestingly, immunofluorescence staining of biofilm-infected tissues revealed increased fibrosis in MyD88 KO mice concomitant with enhanced recruitment of alternatively activated M2 macrophages. Taken in the context of previous studies with IL-1β, TLR2, and TLR9 KO mice, the current report reveals that MyD88 signaling is a major effector pathway regulating fibrosis and macrophage polarization during biofilm formation. Together these findings represent a novel example of the divergence between TLR and MyD88 action in the context of S. aureus biofilm infection.
IL-1RI (interleukin-1 receptor type I) signalling is essential for host defence and hemichannel activity during acute central nervous system bacterial infection
Juan Xiong,Maria Burkovetskaya,Nikolay Karpuk,Tammy Kielian
ASN Neuro , 2012, DOI: 10.1042/an20120008
Abstract: Staphylococcus aureus is a common aetiological agent of bacterial brain abscesses. We have previously established that a considerable IL-1 (interleukin-1) response is elicited immediately following S. aureus infection, where the cytokine can exert pleiotropic effects on glial activation and blood–brain barrier permeability. To assess the combined actions of IL-1α and IL-1β during CNS (central nervous system) infection, host defence responses were evaluated in IL-1RI (IL-1 receptor type I) KO (knockout) animals. IL-1RI KO mice were exquisitely sensitive to intracerebral S. aureus infection, as demonstrated by enhanced mortality rates and bacterial burdens within the first 24 h following pathogen exposure compared with WT (wild-type) animals. Loss of IL-1RI signalling also dampened the expression of select cytokines and chemokines, concomitant with significant reductions in neutrophil and macrophage infiltrates into the brain. In addition, the opening of astrocyte hemichannels during acute infection was shown to be dependent on IL-1RI activity. Collectively, these results demonstrate that IL-1RI signalling plays a pivotal role in the genesis of immune responses during the acute stage of brain abscess development through S. aureus containment, inflammatory mediator production, peripheral immune cell recruitment, and regulation of astrocyte hemichannel activity. Taken in the context of previous studies with MyD88 (myeloid differentiation primary response gene 88) and TLR2 (Toll-like receptor 2) KO animals, the current report advances our understanding of MyD88-dependent cascades and implicates IL-1RI signalling as a major antimicrobial effector pathway during acute brain-abscess formation.
Microglia and Astrocyte Activation by Toll-Like Receptor Ligands: Modulation by PPAR- Agonists
Catherine Gurley,Jessica Nichols,Shuliang Liu,Nirmal K. Phulwani,Nilufer Esen,Tammy Kielian
PPAR Research , 2008, DOI: 10.1155/2008/453120
Abstract: Microglia and astrocytes express numerous members of the Toll-like receptor (TLR) family that are pivotal for recognizing conserved microbial motifs expressed by a wide array of pathogens. Despite the critical role for TLRs in pathogen recognition, when dysregulated these pathways can also exacerbate CNS tissue destruction. Therefore, a critical balance must be achieved to elicit sufficient immunity to combat CNS infectious insults and down-regulate these responses to avoid pathological tissue damage. We performed a comprehensive survey on the efficacy of various PPAR- agonists to modulate proinflammatory mediator release from primary microglia and astrocytes in response to numerous TLR ligands relevant to CNS infectious diseases. The results demonstrated differential abilities of select PPAR- agonists to modulate glial activation. For example, 15d-PGJ2 and pioglitazone were both effective at reducing IL-12 p40 release by TLR ligand-activated glia, whereas CXCL2 expression was either augmented or inhibited by 15d-PGJ2, effects that were dependent on the TLR ligand examined. Pioglitazone and troglitazone demonstrated opposing actions on microglial CCL2 production that were TLR ligand-dependent. Collectively, this information may be exploited to modulate the host immune response during CNS infections to maximize host immunity while minimizing inappropriate bystander tissue damage that is often characteristic of such diseases.
Landmark Optimization Using Local Curvature for Point-Based Nonlinear Rodent Brain Image Registration
Yutong Liu,Balasrinivasa R. Sajja,Mariano G. Uberti,Howard E. Gendelman,Tammy Kielian,Michael D. Boska
International Journal of Biomedical Imaging , 2012, DOI: 10.1155/2012/635207
Abstract: Purpose. To develop a technique to automate landmark selection for point-based interpolating transformations for nonlinear medical image registration. Materials and Methods. Interpolating transformations were calculated from homologous point landmarks on the source (image to be transformed) and target (reference image). Point landmarks are placed at regular intervals on contours of anatomical features, and their positions are optimized along the contour surface by a function composed of curvature similarity and displacements of the homologous landmarks. The method was evaluated in two cases ( each). In one, MRI was registered to histological sections; in the second, geometric distortions in EPI MRI were corrected. Normalized mutual information and target registration error were calculated to compare the registration accuracy of the automatically and manually generated landmarks. Results. Statistical analyses demonstrated significant improvement ( ) in registration accuracy by landmark optimization in most data sets and trends towards improvement ( ) in others as compared to manual landmark selection. 1. Introduction In rodent brains images may become distorted due to instrument imperfections or, in the case of histology, tissue processing. For example, magnetic field inhomogeneity causes geometric distortions in echo planar imaging (EPI) MRI; mechanical forces acting on a harvested brain during slicing may cause tissue tearing. And chemical preparation for histological analysis may cause deformation of tissue, evident in histological micrographs. Correcting (or “rectifying,” “warping”) the distorted images is required to adequately represent rodent brains (in the case of EPI distortion in MRI), or to compare different acquisition modalities (e.g., comparison of in vivo images and histological micrographs). Normally, affine (linear + translation) transformation cannot reconcile severe distortions making nonlinear transformation necessary. Among the nonlinear transformation techniques, point-based interpolating transformation techniques are widely employed because they are easy to implement and flexible for different applications [1–3]. A typical point-based interpolating approach is comprised of three steps: (1) placing homologous point landmarks on the source image (image to be transformed) and the target image (image used as the reference), respectively, (2) computing the interpolating transformation (e.g., polynomial splines, B splines and thin-plate splines [4, 5]) between the source and target images, and (3) aligning the landmarks exactly and
Staphylococcus aureus sarA Regulates Inflammation and Colonization during Central Nervous System Biofilm Formation
Jessica N. Snowden, Matt Beaver, Karen Beenken, Mark Smeltzer, Alexander R. Horswill, Tammy Kielian
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0084089
Abstract: Infection is a frequent and serious complication following the treatment of hydrocephalus with CSF shunts, with limited therapeutic options because of biofilm formation along the catheter surface. Here we evaluated the possibility that the sarA regulatory locus engenders S. aureus more resistant to immune recognition in the central nervous system (CNS) based on its reported ability to regulate biofilm formation. We utilized our established model of CNS catheter-associated infection, similar to CSF shunt infections seen in humans, to compare the kinetics of bacterial titers, cytokine production and inflammatory cell influx elicited by wild type S. aureus versus an isogenic sarA mutant. The sarA mutant was more rapidly cleared from infected catheters compared to its isogenic wild type strain. Consistent with this finding, several pro-inflammatory cytokines and chemokines, including IL-17, CXCL1, and IL-1β were significantly increased in the brain following infection with the sarA mutant versus wild type S. aureus, in agreement with the fact that the sarA mutant displayed impaired biofilm growth and favored a planktonic state. Neutrophil influx into the infected hemisphere was also increased in the animals infected with the sarA mutant compared to wild type bacteria. These changes were not attributable to extracellular protease activity, which is increased in the context of SarA mutation, since similar responses were observed between sarA and a sarA/protease mutant. Overall, these results demonstrate that sarA plays an important role in attenuating the inflammatory response during staphylococcal biofilm infection in the CNS via a mechanism that remains to be determined.
Evidence for Aberrant Astrocyte Hemichannel Activity in Juvenile Neuronal Ceroid Lipofuscinosis (JNCL)
Maria Burkovetskaya, Nikolay Karpuk, Juan Xiong, Megan Bosch, Michael D. Boska, Hideyuki Takeuchi, Akio Suzumura, Tammy Kielian
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095023
Abstract: Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a lysosomal storage disease caused by an autosomal recessive mutation in CLN3 that leads to vision loss, progressive cognitive and motor decline, and premature death. Morphological evidence of astrocyte activation occurs early in the disease process and coincides with regions where neuronal loss eventually ensues. However, the consequences of CLN3 mutation on astrocyte function remain relatively ill-defined. Astrocytes play a critical role in CNS homeostasis, in part, by their ability to regulate the extracellular milieu via the formation of extensive syncytial networks coupled by gap junction (GJ) channels. In contrast, unopposed hemichannels (HCs) have been implicated in CNS pathology by allowing the non-discriminant passage of molecules between the intracellular and extracellular milieus. Here we examined acute brain slices from CLN3 mutant mice (CLN3Δex7/8) to determine whether CLN3 loss alters the balance of GJ and HC activity. CLN3Δex7/8 mice displayed transient increases in astrocyte HC opening at postnatal day 30 in numerous brain regions, compared to wild type (WT) animals; however, HC activity steadily decreased at postnatal days 60 and 90 in CLN3Δex7/8 astrocytes to reach levels lower than WT cells. This suggested a progressive decline in astrocyte function, which was supported by significant reductions in glutamine synthetase, GLAST, and connexin expression in CLN3Δex7/8 mice compared to WT animals. Based on the early increase in astrocyte HC activity, CLN3Δex7/8 mice were treated with the novel carbenoxolone derivative INI-0602 to inhibit HCs. Administration of INI-0602 for a one month period significantly reduced lysosomal ceroid inclusions in the brains of CLN3Δex7/8 mice compared to WT animals, which coincided with significant increases in astrocyte GJ communication and normalization of astrocyte resting membrane potential to WT levels. Collectively, these findings suggest that alterations in astrocyte communication may impact the progression of JNCL and could offer a potential therapeutic target.
Page 1 /238
Display every page Item

Copyright © 2008-2017 Open Access Library. All rights reserved.