Saiepour, Nasrin

[["dc.bibliographiccitation.artnumber","39"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Neuroinflammation"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Ribes, S."],["dc.contributor.author","Zacke, L."],["dc.contributor.author","Nessler, S."],["dc.contributor.author","Saiepour, N."],["dc.contributor.author","Avendaño-Guzmán, E."],["dc.contributor.author","Ballüer, M."],["dc.contributor.author","Hanisch, U. K."],["dc.contributor.author","Nau, R."],["dc.date.accessioned","2021-04-14T08:28:08Z"],["dc.date.accessioned","2022-08-16T13:10:55Z"],["dc.date.available","2021-04-14T08:28:08Z"],["dc.date.available","2022-08-16T13:10:55Z"],["dc.date.issued","2021-02-02"],["dc.date.updated","2022-07-29T12:17:30Z"],["dc.description.abstract","Background\r\n Bacterial meningitis is a fatal disease with a mortality up to 30% and neurological sequelae in one fourth of survivors. Available vaccines do not fully protect against this lethal disease. Here, we report the protective effect of synthetic oligodeoxynucleotides containing unmethylated cytosine-guanine motifs (CpG ODN) against the most frequent form of bacterial meningitis caused by Streptococcus pneumoniae.\r\n \r\n \r\n Methods\r\n Three days prior to the induction of meningitis by intracerebral injection of S. pneumoniae D39, wild-type and Toll-like receptor (TLR9)−/− mice received an intraperitoneal injection of 100 μg CpG ODN or vehicle. To render mice neutropenic, anti-Ly-6G monoclonal antibody was daily administrated starting 4 days before infection with a total of 7 injections. Kaplan-Meier survival analyses and bacteriological studies, in which mice were sacrificed 24 h and 36 h after infection, were performed.\r\n \r\n \r\n Results\r\n Pre-treatment with 100 μg CpG ODN prolonged survival of immunocompetent and neutropenic wild-type mice but not of TLR9−/− mice. There was a trend towards lower mortality in CpG ODN-treated immunocompetent and neutropenic wild-type mice. CpG ODN caused an increase of IL-12/IL-23p40 levels in the spleen and serum in uninfected animals. The effects of CpG ODN on bacterial concentrations and development of clinical symptoms were associated with an increased number of microglia in the CNS during the early phase of infection. Elevated concentrations of IL-12/IL-23p40 and MIP-1α correlated with lower bacterial concentrations in the blood and spleen during infection.\r\n \r\n \r\n Conclusions\r\n Pre-conditioning with CpG ODN strengthened the resistance of neutropenic and immunocompetent mice against S. pneumoniae meningitis in the presence of TLR9. Administration of CpG ODN decreased bacterial burden in the cerebellum and reduced the degree of bacteremia. Systemic administration of CpG ODN may help to prevent or slow the progression to sepsis of bacterial CNS infections in healthy and immunocompromised individuals even after direct inoculation of bacteria into the intracranial compartments, which can occur after sinusitis, mastoiditis, open head trauma, and surgery, including placement of an external ventricular drain."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.citation","Journal of Neuroinflammation. 2021 Feb 02;18(1):39"],["dc.identifier.doi","10.1186/s12974-021-02077-3"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17725"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82510"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112768"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1742-2094"],["dc.relation.orgunit","Institut für Neuropathologie"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject","Oligodeoxynucleotides containing unmethylated cytosine-guanine motifs (CpG ODN)"],["dc.subject","Streptococcus pneumoniae"],["dc.subject","Meningitis"],["dc.subject","Toll-like receptor (TLR) 9"],["dc.subject","Interleukin (IL)-12/IL-23p40"],["dc.subject","Microglia"],["dc.subject","Macrophage inflammatory protein (MIP)-1α"],["dc.title","Oligodeoxynucleotides containing unmethylated cytosine-guanine motifs are effective immunostimulants against pneumococcal meningitis in the immunocompetent and neutropenic host"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","56"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Acta Neuropathologica Communications"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Antonios, Gregory"],["dc.contributor.author","Saiepour, Nasrin"],["dc.contributor.author","Bouter, Yvonne"],["dc.contributor.author","Richard, Bernhard C."],["dc.contributor.author","Paetau, Anders"],["dc.contributor.author","Verkkoniemi-Ahola, Auli"],["dc.contributor.author","Lannfelt, Lars"],["dc.contributor.author","Ingelsson, Martin"],["dc.contributor.author","Kovacs, Gabor G."],["dc.contributor.author","Pillot, Thierry"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Bayer, Thomas A."],["dc.date.accessioned","2019-07-09T11:41:53Z"],["dc.date.available","2019-07-09T11:41:53Z"],["dc.date.issued","2013"],["dc.description.abstract","Abstract Background The amyloid hypothesis in Alzheimer disease (AD) considers amyloid β peptide (Aβ) deposition causative in triggering down-stream events like neurofibrillary tangles, cell loss, vascular damage and memory decline. In the past years N-truncated Aβ peptides especially N-truncated pyroglutamate AβpE3-42 have been extensively studied. Together with full-length Aβ1–42 and Aβ1–40, N-truncated AβpE3-42 and Aβ4–42 are major variants in AD brain. Although Aβ4–42 has been known for a much longer time, there is a lack of studies addressing the question whether AβpE3-42 or Aβ4–42 may precede the other in Alzheimer’s disease pathology. Results Using different Aβ antibodies specific for the different N-termini of N-truncated Aβ, we discovered that Aβ4-x preceded AβpE3-x intraneuronal accumulation in a transgenic mouse model for AD prior to plaque formation. The novel Aβ4-x immunoreactive antibody NT4X-167 detected high molecular weight aggregates derived from N-truncated Aβ species. While NT4X-167 significantly rescued Aβ4–42 toxicity in vitro no beneficial effect was observed against Aβ1–42 or AβpE3-42 toxicity. Phenylalanine at position four of Aβ was imperative for antibody binding, because its replacement with alanine or proline completely prevented binding. Although amyloid plaques were observed using NT4X-167 in 5XFAD transgenic mice, it barely reacted with plaques in the brain of sporadic AD patients and familial cases with the Arctic, Swedish and the presenilin-1 PS1Δ9 mutation. A consistent staining was observed in blood vessels in all AD cases with cerebral amyloid angiopathy. There was no cross-reactivity with other aggregates typical for other common neurodegenerative diseases showing that NT4X-167 staining is specific for AD. Conclusions Aβ4-x precedes AβpE3-x in the well accepted 5XFAD AD mouse model underlining the significance of N-truncated species in AD pathology. NT4X-167 therefore is the first antibody reacting with Aβ4-x and represents a novel tool in Alzheimer research."],["dc.identifier.doi","10.1186/2051-5960-1-56"],["dc.identifier.pmid","24252153"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12500"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58537"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","N-truncated Abeta starting with position four: early intraneuronal accumulation and rescue of toxicity using NT4X-167, a novel monoclonal antibody"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]