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Characterization of the temporo-spatial effects of chronic bilateral intrahippocampal cannulae on interleukin-1beta.

ABSTRACT: The implantation of a foreign object in the brain produces an acute neuroinflammatory state in which glia (astrocytes and microglia) may remain chronically activated in response to the inert foreign object. Activated glia can exhibit a sensitized pro-inflammatory response to immunogenic stimuli. This may be relevant to intracranial cannula implantation, which is commonly used to administer substances directly into the brain. If intracranial cannulation activates glia, a subsequent neuroinflammatory stimulus might induce a potentiated pro-inflammatory response, thereby introducing a potential experimental confound. We tested the temporal and spatial responses of interleukin-1beta (IL-1beta) to an acute immune challenge produced by lipopolysaccharide (LPS) in animals with chronic bilateral intrahippocampal cannulae implants (stainless steel). Cannulation increased the gene expression of the microglia activation antigens MHC II and CD11b, but not the astrocyte antigen GFAP. Moreover, this activation was temporally and spatially dependent. In addition, IL-1beta mRNA, but not IL-1beta protein, was significantly elevated in cannulated animals. Administration of LPS, however, significantly potentiated the brain IL-1beta response in cannulated animals, but not in stab wounded or naïve animals. This IL-1beta response was also temporo-spatially dependent. Thus, the pro-inflammatory sequelae of intracranial cannulation should be considered when designing studies of neuroinflammatory processes.

SUBMITTER: Holguin A

PROVIDER: S-EPMC2464278 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

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Characterization of the temporo-spatial effects of chronic bilateral intrahippocampal cannulae on interleukin-1beta.

Holguin Adelina A Frank Matthew G MG Biedenkapp Joseph C JC Nelson Kristen K Lippert Dylan D Watkins Linda R LR Rudy Jerry W JW Maier Steven F SF

Journal of neuroscience methods 20070122 2

The implantation of a foreign object in the brain produces an acute neuroinflammatory state in which glia (astrocytes and microglia) may remain chronically activated in response to the inert foreign object. Activated glia can exhibit a sensitized pro-inflammatory response to immunogenic stimuli. This may be relevant to intracranial cannula implantation, which is commonly used to administer substances directly into the brain. If intracranial cannulation activates glia, a subsequent neuroinflammat ...[more]

PMID: 17241670

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Project description:Chronic pancreatitis is a significant cause of morbidity and a known risk factor for pancreatic adenocarcinoma. Interleukin-1beta is a proinflammatory cytokine involved in pancreatic inflammation. We sought to determine whether targeted overexpression of interleukin-1beta in the pancreas could elicit localized inflammatory responses and chronic pancreatitis.We created a transgenic mouse model (elastase sshIL-1beta) in which the rat elastase promoter drives the expression of human interleukin-1beta. Mice were followed up for up to 2 years. Pancreata of elastase sshIL-1beta mice were analyzed for chronic pancreatitis-associated histologic and molecular changes. To study the potential effect of p53 mutation in chronic pancreatitis, elastase sshIL-1beta mice were crossed with p53(R172H) mice.Three transgenic lines were generated, and in each line the pancreas was atrophic and occasionally showed dilation of pancreatic and biliary ducts secondary to proximal fibrotic stenosis. Pancreatic histology showed typical features of chronic pancreatitis. There was evidence for increased acinar proliferation and apoptosis, along with prominent expression of tumor necrosis factor-alpha; chemokine (C-X-C motif) ligand 1; stromal cell-derived factor 1; transforming growth factor-beta1; matrix metallopeptidase 2, 7, and 9; inhibitor of metalloproteinase 1; and cyclooxygenase 2. The severity of the lesions correlated well with the level of human interleukin-1beta expression. Older mice displayed acinar-ductal metaplasia but did not develop mouse pancreatic intraepithelial neoplasia or tumors. Elastase sshIL-1beta*p53(R172H/+) mice had increased frequency of tubular complexes, some of which were acinar-ductal metaplasia.Overexpression of interleukin-1beta in the murine pancreas induces chronic pancreatitis. Elastase sshIL-1beta mice consistently develop severe chronic pancreatitis and constitute a promising model for studying chronic pancreatitis and its relationship with pancreatic adenocarcinoma.

Project description:BackgroundAdrenomedullin (AM) is a potent vasodilator peptide and is also involved in various physiological activities. In humans and rodents, AM is found in the uteroplacental unit and may be responsible for fetal development and maintenance of placental function. This study investigated 1) the mRNA expression patterns of AM and its receptor components (calcitonin receptor-like receptor (CRLR), receptor activity modifying protein (RAMP) 2 and RAMP3) during pregnancy and 2) mRNA and protein localization of AM, CRLR and RAMPs in the bovine placentome.MethodsFor real-time quantitative RT-PCR, bovine uteroplacental tissues were collected from Day 25, 60, 100, 150, 200 and 250 of gestation and separated into uterine caruncle (CAR), intercaruncular endometrium (ICAR), extra-embryonic membranes on Day 25 and cotyledonary villous after Day 60 (EEM-COT) and intercotyledonary chorion (ICOT). In situ hybridization and immunohistochemistry was performed to investigate the cellular localization of mRNA and protein of AM, CRLR, RAMP2 and RAMP3 in the placentome on Day 56, 150 and 230 of gestation and interplacentomal tissues on Day 56 of gestation.ResultsAM mRNA was highly expressed on Day 200 in EEM-COT, CAR and ICAR. CRLR mRNA was highly expressed on Day 60 in all portions. RAMP2 mRNA was also highly expressed on Day 60 in ICOT and ICAR. In EEM-COT, mRNA expression of CRLR and RAMP2 decreased from Day 150 to 250. RAMP3 mRNA was highly expressed on Day 150 in EEM-COT, ICOT and ICAR. A distinct AM mRNA and protein signal were only found in trophoblast binucleate cells (BNCs), whereas those of CRLR, RAMP2 and RAMP3 were detected in cotyledonary villous and caruncular epithelial cells. In interplacentomal tissues, AM was detected in BNCs of fetal membrane and a small part of luminal epithelium, endothelial lineage of blood vessels and glandular epithelium of the endometrium. Distinct signals of CRLR, RAMP2 and RAMP3 were found in trophoblast cells, luminal epithelium, stroma under the epithelium, endothelial lineage of blood vessels and glandular epithelium.ConclusionsOur results indicate that the AM system in the bovine uteroplacental unit may be activated at placentation and transition from the mid to late gestation period. Locally produced AM in the BNCs may play a crucial role in regulation of placental vascular and cellular functions during pregnancy.

Dataset Information

Characterization of the temporo-spatial effects of chronic bilateral intrahippocampal cannulae on interleukin-1beta.

Publications

Characterization of the temporo-spatial effects of chronic bilateral intrahippocampal cannulae on interleukin-1beta.

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