Equine borna disease in Japan.
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Animals↗
Biomedical subjects
A Pagenstecher
Publications and source records attributed to A Pagenstecher.
Combined stent implantation and embolization with liquid 2-polyhydroxyethyl methacrylate for treatment of experimental canine wide-necked aneurysms.
The purpose of the study was the evaluation of 2-polyhydroxyethyl methacrylate (2-P-HEMA) for endovascular liquid embolization of experimental side-wall aneurysms following stent protection in a canine model. The swelling behaviour and polymerization characteristics of 2-P-HEMA in different solutions were investigated in vitro. Different methods for applications were tested in a latex aneurysm model under pulsatile flow conditions. Twenty broad-based carotid side-wall aneurysms were microsurgically produced in five dogs. Four weeks after surgery self-expandable nitinol stents were placed, covering the orifice of the aneurysms. 2-P-HEMA was injected via a microcatheter, which was positioned through the meshwork of the stent. Control angiography was performed immediately after treatment and after 1, 6 and 9 months. In-vivo stent placement succeeded in all but one case. Two aneurysms occluded spontaneously after stent placement. Combined embolization of 17 aneurysms using a stent and 2-P-HEMA was performed. Eleven aneurysms could be primarily completely occluded (65%). A small remaining neck was evident in six aneurysms. Efflux of 2-P-HEMA during the process of embolization was observed in seven aneurysms, due to an excess volume of 2-P-HEMA. The excessive 2-P-HEMA led to significant vessel stenosis in two cases. Two carotid arteries (three treated aneurysms) occluded after 1 month, due to insufficient anticoagulation management. Histological examination of embolized aneurysms revealed no foreign-body or inflammatory reaction. A smooth neo-intimal layer covered the stented vessel segment. Liquid embolization of side-wall aneurysms with 2-P-HEMA is technically feasible. Embolotherapy of aneurysms with liquid agents still has the risk that embolic material will exit even when it is stent-protected. To avoid this problem, stents with smaller strut diameter and/or additional balloon-protection are required. The inert 2-P-HEMA seems to be a promising agent for combining techniques of aneurysm treatment.
Aneurysm↗
Gliosarcoma: a clinical study.
BACKGROUND AND PURPOSE: Gliosarcomas are rare biphasic neoplasms of the central nervous system composed of a glioblastoma multiforme (GBM) admixed with a sarcomatous component. There are conflicting reports regarding their clinical aggressiveness. Four hundred and twenty-two consecutive patients with GBM were treated at our hospital between 1980 and 1999, among them 12 gliosarcomas. The goal of this study was to examine clinical features, treatment, survival and patterns of failure of gliosarcoma patients and to compare them with the entire group of GBM patients. This comparison was refined by a matched pair analysis with a group of 12 GBM patients selected for age, Karnofsky performance status, resection status, fractionation scheme and total dose (control GBM group). MATERIALS AND METHODS: Seven gliosarcoma patients were male, five female, with a median age of 56 years (range 37-76 years). The median tumor size was 4.5 cm (range 3-8 cm). The locations, all supratentorial, included temporal in six, parietal in five, frontal in four and occipital in one patient. All patients underwent tumor resection followed by postoperative radiation therapy. RESULTS: Median survival was 11.5 months for the gliosarcoma group, 8.1 months for the entire GBM group (log rank test, P=0.16) and 11.0 months for the control GBM group (log rank test, P=0.36). All gliosarcoma patients had local tumor recurrences and died due to neurologic causes within 19.3 months after radiation therapy. CONCLUSIONS: With regard to clinical features, survival and patterns of failure, gliosarcomas and GBM cannot be distinguished clinically. Therefore, the same principles should be applied for the treatment of these tumors.
Adult↗
Atypical teratoid/rhabdoid tumors in adult patients: case report and review of the literature.
Atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system are rare and extremely aggressive malignancies of early childhood. We report a case of AT/RT in an adult patient. A 30-year-old woman presented with headache, vomiting and ataxia during the second trimester of pregnancy. Magnetic resonance imaging revealed a posterior fossa mass. A gross total resection was performed. Pathological examination revealed an AT/RT. Despite the dismal prognosis the patient decided not to undergo an abortion. For this reason postoperative accelerated hyperfractionated radiotherapy was limited to the tumor region. Six months later the woman delivered a healthy baby. One week postpartum, a central nervous system recurrence localized apart from the primary lesion was treated with radiosurgery. Two months later a diffuse progression was noted. Despite a 6 week course of oral temozolomide, the tumor progressed and the patient died 11 months after diagnosis. Although survival was short, surgery and involved field radiotherapy yielded a progression-free interval of 9 months. This allowed the patient to carry pregnancy to term. Radiosurgery resulted in a complete remission of the first recurrence. Oral chemotherapy was not effective in controlling diffuse tumor spread.
Adult↗
Distinct expression patterns and levels of enzymatic activity of matrix metalloproteinases and their inhibitors in primary brain tumors.
Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been implicated in the immense invasive potential and neovascularization of primary brain tumors. We investigated the gene expression profiles of MMPs 1, 2, 3, 7, 9, 12, 13, 14, 16 and of TIMPs 1, 2, 3, and 4 in various primary brain tumors (astrocytoma WHO grade I-III, glioblastoma, PNET, ependymoma III and oligoastrocytoma II) using novel RNase protection assay probe sets. In addition, we determined the level and cellular source of gelatinolytic activity and localized gelatinase B and TIMP-1 RNA. Distinct expression patterns of the MMP and TIMP genes were found in the various brain tumors tested. While the WHO grade I and II tumors had MT1/MT3 ratios below 1, the malignant (grade III and IV) tumors had ratios above 1. Strong expression of TIMP-1 RNA was observed in all malignant tumors and in grade I pilocytic astrocytomas and localized to the walls of neovessels. Quantitative analysis of enzymatic activity in the soluble fraction of protein extracts revealed that in most tumors gelatinases remained in the inactive pro-form. In situ zymography revealed net gelatinolytic activity in neurons of normal brain and in tumor cells and vessel walls of all tumors tested. Immunohistochemistry demonstrated that gelatinase B was localized to vessel walls, to neutrophils in areas of hemorrhage, and in glioblastomas to macrophages. Together these data demonstrate that the different primary brain tumors show distinct regulation of MMP and TIMP genes. The localization of the soluble gelatinase B indicates an association with neovascularization, whereas membrane-bound MMPs may account for the invasive potential of the glial tumor cells.
Brain↗
Alpha/beta interferon promotes transcription and inhibits replication of borna disease virus in persistently infected cells.
Borna disease virus (BDV) is a noncytolytic RNA virus that can replicate in the central nervous system (CNS) of mice. This study shows that BDV multiplication was efficiently blocked in transgenic mice that express mouse alpha-1 interferon (IFN-alpha1) in astrocytes. To investigate whether endogenous virus-induced IFN might similarly restrict BDV, we used IFNAR(0/0) mice, which lack a functional alpha/beta IFN (IFN-alpha/beta) receptor. As would be expected if virus-induced IFN were important to control BDV infection, we found that cultured embryo cells of IFNAR(0/0) mice supported viral multiplication, whereas cells from wild-type mice did not. Unexpectedly, however, BDV spread through the CNSs of IFNAR(0/0) and wild-type mice with similar kinetics, suggesting that activation of endogenous IFN-alpha/beta genes in BDV-infected brains was too weak or occurred too late to be effective. Surprisingly, Northern blot analysis showed that the levels of the most abundant viral mRNAs in the brains of persistently infected IFNAR(0/0) mice were about 20-fold lower than those in wild-type mice. In contrast, genomic viral RNA was produced in about a 10-fold excess in the brains of IFNAR(0/0) mice. Human IFN-alpha2 similarly enhanced transcription and simultaneously repressed replication of the BDV genome in persistently infected Vero cells. Thus, in persistently infected neurons and cultured cells, IFN-alpha/beta appears to freeze the BDV polymerase in the transcriptional mode, resulting in enhanced viral mRNA synthesis and suppressing viral genome replication.
Animals↗
Morbillivirus infection of the mouse central nervous system induces region-specific upregulation of MMPs and TIMPs correlated to inflammatory cytokine expression.
Viral infection of the central nervous system (CNS) can result in perturbation of cell-to-cell communication involving the extracellular matrix (ECM). ECM integrity is maintained by a dynamic balance between the synthesis and proteolysis of its components, mainly as a result of the action of matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). An MMP/TIMP imbalance may be critical in triggering neurological disorders, in particular in virally induced neural disorders. In the present study, a mouse model of brain infection using a neurotropic strain of canine distemper virus (CDV) was used to study the effect of CNS infection on the MMP/TIMP balance and cytokine expression. CDV replicates almost exclusively in neurons and has a unique pattern of expression (cortex, hypothalamus, monoaminergic nuclei, hippocampus, and spinal cord). Here we show that although several mouse brain structures were infected, they exhibited a differential pattern in terms of MMP, TIMP, and cytokine expression, exemplified by (i) a large increase in pro-MMP9 levels, in particular in the hippocampus, which occurred mainly in neurons and was associated with in situ gelatinolytic activity, (ii) specific and significant upregulation of MT1-MMP mRNA expression in the cortex and hypothalamus, (iii) an MMP/TIMP imbalance, suggested by the upregulation of TIMP-1 mRNA in the cortex, hippocampus, and hypothalamus and of TIMP-3 mRNA in the cortex, and (iv) a concomitant region-specific large increase in expression of Th1-like cytokines, such as gamma interferon, tumor necrosis factor alpha, and interleukin 6 (IL-6), contrasting with weaker induction of Th2-like cytokines, such as IL-4 and IL-10. These data indicate that an MMP/TIMP imbalance in specific brain structures, which is tightly associated with a local inflammatory process as shown by the presence of immune infiltrating cells, differentially impairs CNS integrity and may contribute to the multiplicity of late neurological disorders observed in this viral mouse model.
Animals↗
Astrocyte-targeted expression of IL-12 induces active cellular immune responses in the central nervous system and modulates experimental allergic encephalomyelitis.
The role of IL-12 in the evolution of immunoinflammatory responses at a localized tissue level was investigated. Transgenic mice were developed with expression of either both the IL-12 subunits (p35 and p40) or only the IL-12 p40 subunit genes targeted to astrocytes in the mouse CNS. Glial fibrillary acidic protein (GF)-IL-12 mice, bigenic for the p35 and p40 genes, developed neurologic disease which correlated with the levels and sites of transgene-encoded IL-12 expression. In these mice, the brain contained numerous perivascular and parenchymal inflammatory lesions consisting of predominantly CD4+ and CD8+ T cells as well as NK cells. The majority of the infiltrating T cells had an activated phenotype (CD44high, CD45Rblow, CD62Llow, CD69high, VLA-4 high, and CD25+). Functional activation of the cellular immune response was also evident with marked cerebral expression of the IFN-gamma, TNF, and IL-1alphabeta genes. Concomitant with leukocyte infiltration, the CNS expression of immune accessory molecules was induced or up-regulated, including ICAM-1, VCAM-1, and MHC class II and B7-2. Glial fibrillary acidic protein-p40 mice with expression of IL-12 p40 alone remained asymptomatic, with no inflammation evident at any age studied. The effect of local CNS production of IL-12 in the development of experimental autoimmune encephalomyelitis was studied. After immunization with myelin oligodendrocyte glycoprotein-peptides, GF-IL-12 mice had an earlier onset and higher incidence but not more severe disease. We conclude that localized expression of IL-12 by astrocytes can 1) promote the spontaneous development of activated type 1 T cell and NK cellular immunity and cytokine responses in the CNS, and 2) promote more effective Ag-specific T cell dynamics but not activity in experimental autoimmune encephalomyelitis.
Animals↗
Supratentorial primitive neuroectodermal tumours: diffusion-weighted MRI.
We report the clinical and pathological findings of supratentorial primitive neuroectodermal tumours (PNETs). These are rare, poorly differentiated, highly malignant neoplasms occurring primarily in young individuals. They frequently show dissemination to the spinal cord and sometimes also beyond neuraxis. Preoperative radiological diagnosis is difficult, due to the nonspecific CT and MRI characteristics. Our findings indicate that diffusion-weighted imaging (DWI) can be used to show the solid portion of the tumour preoperatively and to monitor postsurgical recovery. We describe the MRI findings in three patients with histologically confirmed supratentorial PNET, focussing on the role of DWI for improving the specificity of radiological diagnosis.
Child↗
Regulation of matrix metalloproteinases and their inhibitor genes in lipopolysaccharide-induced endotoxemia in mice.
An imbalance between matrix metalloproteinases (MMPs) and inhibitors of MMPs (TIMPs) may contribute to tissue destruction that is found in various inflammatory disorders. To determine in an in vivo experimental setting whether the inflammatory reaction in the course of lipopolysaccharide (LPS)-induced endotoxemia causes an altered balance in the MMP/TIMP system, we analyzed the expression of a number of MMP and TIMP genes as well as MMP enzymatic activity in the liver, kidney, spleen, and brain at various time points after systemic injection of different doses of LPS in mice. Injection of sublethal doses of LPS led to an organ- and time-specific pattern of up-regulation of several MMP genes and the TIMP-1 gene in the liver, spleen, and kidney, whereas in the brain only TIMP-1 was induced. Injection of a lethal dose of LPS caused similar but more prolonged expression of these MMP genes as well as the induction of additional MMP genes in all organs. In LPS-treated mice in situ hybridization revealed collagenase 3 gene induction in cells resembling macrophages whereas TIMP-1 RNA was detected predominantly in parenchymal cells. Finally, gelatin zymography revealed increased gelatinolytic activity in all organs after LPS treatment. These observations highlight a dramatic shift in favor of increased expression of the MMP genes over the TIMP genes during LPS-induced endotoxemia, and suggest that MMPs may contribute to the development of organ damage in endotoxemia.
Animals↗
Chemokine gene expression in astrocytes of Borna disease virus-infected rats and mice in the absence of inflammation.
Borna disease virus (BDV) causes CD8(+) T-cell-mediated meningoencephalitis in immunocompetent mice and rats, thus providing a valuable animal model for studying the mechanisms of virus-induced central nervous system (CNS) immunopathology. Chemokine-mediated leukocyte recruitment to the CNS is a crucial step in the development of neurological disease. We found increased mRNA levels of IP-10 and other chemokines in brains of adult rats following infection with BDV. The marked increase in chemokine gene expression at about day 8 postinfection seemed to immediately precede the inflammatory process. In brains of rats infected as newborns, in which inflammation was only mild and transient, sustained expression of IP-10 and RANTES genes was observed. In situ hybridization studies revealed that astrocytes were the major source of IP-10 mRNAs in brains of rats infected as newborns and as adults. In brains of infected mice lacking CD8(+) T cells (beta2m(0/0)), transcripts encoding IP-10 and RANTES were also observed. IP-10 transcripts were also present in a small number of scattered astrocytes of infected knockout mice lacking mature B and T cells as well as functional alpha/beta and gamma interferon receptors, indicating that BDV can induce chemokine synthesis in the absence of interferons and other B- or T-cell-derived cytokines. These data provide strong evidence that CNS-resident cells are involved in the early localized host immune response to infection with BDV and support the concept that chemokines are pivotal for the initiation of virus-induced CNS inflammation.
Animals↗
T cell ignorance in mice to Borna disease virus can be overcome by peripheral expression of the viral nucleoprotein.
Infection of neonates with Borna disease virus (BDV) induces severe meningoencephalitis and neurological disorder in wild-type but not in beta(2)-microglobulin-deficient mice of strain MRL (H-2(k)). Temporary in vivo depletion of CD8(+) T cells delayed BDV-induced disease for several weeks. Depletion of CD4(+) T cells had a similar beneficial effect, indicating that the BDV-induced neurological disorder in mice is a CD4(+) T cell-dependent immunopathological process that is mediated by CD8(+) T cells. Lymphocytes prepared from brains of diseased mice were mainly from the CD8(+) T cell subset. They showed up-regulation of activation markers and exerted strong MHC I-restricted cytotoxic activity against target cells expressing the BDV nucleoprotein p40. Infection of B10.BR (H-2(k)) or congenic C57BL/10 (H-2(b)) mice resulted in symptomless, lifelong persistence of BDV in the brain. Superinfection with a recombinant vaccinia virus expressing BDV p40 but not with other vaccinia viruses induced severe neurological disease and encephalitis in persistently infected B10.BR mice but not in persistently infected C57BL/10 mice, indicating that the disease-inducing T cell response is restricted to the nucleoprotein of BDV in H-2(k) mice. Our results demonstrate that the cellular arm of the immune system may ignore the presence of a replicating virus in the central nervous system until proper antigenic stimulation at a peripheral site triggers the antiviral response.
Animals↗
C10 is a novel chemokine expressed in experimental inflammatory demyelinating disorders that promotes recruitment of macrophages to the central nervous system.
Chemokines may be important in the control of leukocytosis in inflammatory disorders of the central nervous system. We studied cerebral chemokine expression during the evolution of diverse neuroinflammatory disorders in transgenic mice with astrocyte glial fibrillary acidic protein-targeted expression of the cytokines IL-3, IL-6, or IFN-alpha and in mice with experimental autoimmune encephalomyelitis. Distinct chemokine gene expression patterns were observed in the different central nervous system inflammatory models that may determine the phenotype and perhaps the functions of the leukocytes that traffic into the brain. Notably, high expression of C10 and C10-related genes was found in the cerebellum and spinal cord of GFAP-IL3 mice with inflammatory demyelinating disease and in mice with experimental autoimmune encephalomyelitis. In both these neuroinflammatory models, C10 RNA and protein expressing cells were predominantly macrophage/microglia and foamy macrophages present within demyelinating lesions as well as in perivascular infiltrates and meninges. Intracerebroventricular injection of recombinant C10 protein promoted the recruitment of large numbers of Mac-1(+) cells and, to a much lesser extent, CD4(+) lymphocytes into the meninges, choroid plexus, ventricles, and parenchyma of the brain. Thus, C10 is a prominent chemokine expressed in the central nervous system in experimental inflammatory demyelinating disease that, we show, also acts as a potent chemotactic factor for the migration of these leukocytes to the brain.
Age Factors↗
Matrix metalloproteinases and their inhibitors in the nervous system: the good, the bad and the enigmatic.
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Animals↗
Late-onset chronic inflammatory encephalopathy in immune-competent and severe combined immune-deficient (SCID) mice with astrocyte-targeted expression of tumor necrosis factor.
To examine the role of tumor necrosis factor (TNF)-alpha in the pathogenesis of degenerative disorders of the central nervous system (CNS), transgenic mice were developed in which expression of murine TNF-alpha was targeted to astrocytes using a glial fibrillary acidic protein (GFAP)-TNF-alpha fusion gene. In two independent GFAP-TNFalpha transgenic lines (termed GT-8 or GT-2) adult (>4 months of age) animals developed a progressive ataxia (GT-8) or total paralysis affecting the lower body (GT-2). Symptomatic mice had prominent meningoencephalitis (GT-8) or encephalomyelitis (GT-2) in which large numbers of B cells and CD4+ and CD8+ T cells accumulated at predominantly perivascular sites. The majority of these lymphocytes displayed a memory cell phenotype (CD44high, CD62Llow, CD25-) and expressed an early activation marker (CD69). Parenchymal lesions contained mostly CD45+ high, MHC class II+, and Mac-1+ cells of the macrophage microglial lineage with lower numbers of neutrophils and few CD4+ and CD8+ T cells. Cerebral expression of the cellular adhesion molecules ICAM-1, VCAM-1, and MAdCAM as well as a number of alpha- and beta-chemokines was induced or upregulated and preceded the development of inflammation, suggesting an important signaling role for these molecules in the CNS leukocyte migration. Degenerative changes in the CNS of the GFAP-TNFalpha mice paralleled the development of the inflammatory lesions and included primary and secondary demyelination and neurodegeneration. Disease exacerbation with more extensive inflammatory lesions that contained activated cells of the macrophage/microglial lineage occurred in GFAP-TNFalpha mice with severe combined immune deficiency. Thus, persistent astrocyte expression of murine TNF-alpha in the CNS induces a late-onset chronic inflammatory encephalopathy in which macrophage/microglial cells but not lymphocytes play a central role in mediating injury.
Animals↗
Borna disease virus-induced neurological disorder in mice: infection of neonates results in immunopathology.
Borna disease virus (BDV) is a neurotropic nonsegmented negative-stranded RNA virus that persistently infects warm-blooded animals. In horses and other natural animal hosts, infections with BDV cause meningoencephalitis and behavioral disturbances. Experimental infection of adult mice takes a nonsymptomatic course, an observation previously believed to indicate that this animal species is not suitable for pathogenesis studies. We now demonstrate that BDV frequently induces severe neurological disease in infected newborn mice. Signs of neurological disease were first observed 4 to 6 weeks after intracerebral infection. They included a characteristic nonphysiological position of the hind limbs at an early stage of the disease and paraparesis at a later stage. Histological examination revealed large numbers of perivascular and meningeal inflammatory cells in brains of diseased mice and, unexpectedly, no increase in immunoreactivity to glial fibrillar acidic protein. The incidence and severity of BDV-induced disease varied dramatically among mouse strains. While only 13% of the infected C57BL/6 mice showed disease symptoms, which were mostly transient, more than 80% of the infected MRL mice developed severe neurological disorder. In spite of these differences in susceptibility to disease, BDV replicated to comparable levels in the brains of mice of the various strains used. Intracerebral infections of newborn beta2-microglobulin-deficient C57BL/6 and MRL mice, which both lack CD8+ T cells, did not result in meningoencephalitis or neurological disease, indicating that the BDV-induced neurological disorder in mice is a cytotoxic T-cell-mediated immunopathological process. With this new animal model it should now be possible to characterize the disease-inducing immune response to BDV in more detail.
Animals↗
Differential expression of matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase genes in the mouse central nervous system in normal and inflammatory states.
Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of inflammatory disorders of the central nervous system (CNS) whereas the contribution of the major endogenous counter-regulators of MMPs, the tissue inhibitors of the matrix metalloproteinases (TIMPs), is unclear. We investigated the temporal and spatial expression patterns in the CNS of nine MMP genes and three TIMP genes in normal mice, in mice with EAE, and in transgenic mice with astrocyte (glial fibrillary acidic protein)-targeted expression of the cytokines interleukin-3 (macrophage/microglial demyelinating disease), interleukin-6 (neurodegenerative disease), or tumor necrosis factor-alpha (lymphocytic encephalomyelitis). In normal mice, the MMPs MT1-MMP, stromelysin 3, and gelatinase B were expressed at low levels, whereas high expression of TIMP-2 and TIMP-3 was observed predominantly in neurons and in the choroid plexus, respectively. In EAE and the transgenic mice, significant induction or up-regulation of various MMP genes was observed, the pattern of which was somewhat specific for each of the models, and there was significant induction of TIMP-1. In situ localization experiments revealed a dichotomy between MMP expression that was restricted to leukocytes and possibly microglia within inflammatory lesions and TIMP-1 expression that was observed in activated astrocytes circumscribing the lesions. These findings demonstrate specific spatial and temporal regulation in the expression of individual MMP and TIMP genes in the CNS in normal and inflammatory states. The distinct localization of TIMP-1 and MMP expression during CNS inflammation suggests a dynamic state in which the interplay between these gene products may determine both the size and resolution of the destructive inflammatory focus.
Animals↗
RNAse protection assays for the simultaneous and semiquantitative analysis of multiple murine matrix metalloproteinase (MMP) and MMP inhibitor mRNAs.
Matrix metalloproteinases (MMPs) are a family of proteinases that play a major role in the metabolic degradation of extracellular matrix proteins. In order to examine the expression pattern of different MMP or MMP-inhibitor genes two RNase protection assays (RPAs) were developed that allow the simultaneous and semiquantitative assessment of their respective mRNAs. Probes for the detection of MMPs stromelysin 1, 2 and 3, matrilysin, metalloelastase, gelatinase A and B, collagenase and membrane type MMP (MT1-MMP) were included in the first RPA probe set, while probes for tissue inhibitor of matrix metalloproteinase (TIMP) 1, 2, 3 and alpha 2-macroglobulin (alpha 2-M) were included in the second probe set (inhibitor of matrix metalloproteinase-IMP set). Titration experiments revealed that this method allows the detection of MMP and inhibitor mRNAs present in at least 0.03 microgram of spleen poly(A)+ RNA. Both RPA sets were further evaluated by analyzing the expression of MMP and IMP genes in brain, kidney, spleen and liver in a murine model for endotoxemia after intraperitoneal LPS injection. Control animals showed an organ-specific constitutive expression of one or more MMPs and a high expression of TIMPs. Following LPS injection, an organ-specific upregulation or induction of MMP and TIMP RNA species was found. This change was most pronounced in the spleen, while liver, kidney and brain showed minor or no changes in MMP expression. An IMP upregulation was detected in all organs. These RPA probe sets provide a valuable tool for the simultaneous assessment of MMP and IMP gene expression under physiological and pathological conditions.
Animals↗