{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T17:11:23Z","timestamp":1776705083259,"version":"3.51.2"},"reference-count":66,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2013,8,27]],"date-time":"2013-08-27T00:00:00Z","timestamp":1377561600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Bacterial meningitis caused by<jats:italic>Streptococcus pneumonia<\/jats:italic>e leads to death in up to 30% of patients and leaves up to half of the survivors with neurological sequelae. The inflammatory host reaction initiates the induction of the kynurenine pathway and contributes to hippocampal apoptosis, a form of brain damage that is associated with learning and memory deficits in experimental paradigms. Vitamin B6 is an enzymatic cofactor in the kynurenine pathway and may thus limit the accumulation of neurotoxic metabolites and preserve the cellular energy status.<\/jats:p><jats:p>The aim of this study in a pneumococcal meningitis model was to investigate the effect of vitamin B6 on hippocampal apoptosis by histomorphology, by transcriptomics and by measurement of cellular nicotine amide adenine dinucleotide content.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Eleven day old Wistar rats were infected with 1x10<jats:sup>6<\/jats:sup>cfu\/ml of<jats:italic>S<\/jats:italic>.<jats:italic>pneumoniae<\/jats:italic>and randomized for treatment with vitamin B6 or saline as controls. Vitamin B6 led to a significant (p &gt; 0.02) reduction of hippocampal apoptosis. According to functional annotation based clustering, vitamin B6 led to down-regulation of genes involved in processes of inflammatory response, while genes encoding for processes related to circadian rhythm, neuronal signaling and apoptotic cell death were mostly up-regulated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results provide evidence that attenuation of apoptosis by vitamin B6 is multi-factorial including down-modulation of inflammation, up-regulation of the neuroprotective brain-derived neurotrophic factor and prevention of the exhaustion of cellular energy stores. The neuroprotective effect identifies vitamin B6 as a potential target for the development of strategies to attenuate brain injury in bacterial meningitis.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2334-13-393","type":"journal-article","created":{"date-parts":[[2013,8,27]],"date-time":"2013-08-27T06:14:36Z","timestamp":1377584076000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Vitamin B6 reduces hippocampal apoptosis in experimental pneumococcal meningitis"],"prefix":"10.1186","volume":"13","author":[{"given":"Denise C","family":"Zysset-Burri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline L","family":"Bellac","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen L","family":"Leib","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Wittwer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,8,27]]},"reference":[{"key":"2599_CR1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1542\/peds.95.5.646","volume":"95","author":"K Grimwood","year":"1995","unstructured":"Grimwood K, Anderson VA, Bond L, Catroppa C, Hore RL, Keir EH, Nolan T, Roberton DM: Adverse outcomes of bacterial meningitis in school-age survivors. Pediatrics. 1995, 95: 646-656.","journal-title":"Pediatrics"},{"key":"2599_CR2","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1097\/NEN.0b013e3181f7e7e9","volume":"69","author":"CL Bellac","year":"2010","unstructured":"Bellac CL, Coimbra RS, Christen S, Leib SL: Inhibition of the kynurenine-NAD+ pathway leads to energy failure and exacerbates apoptosis in pneumococcal meningitis. J Neuropathol Exp Neurol. 2010, 69: 1096-1104. 10.1097\/NEN.0b013e3181f7e7e9.","journal-title":"J Neuropathol Exp Neurol"},{"key":"2599_CR3","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/S1473-3099(02)00450-4","volume":"2","author":"U Koedel","year":"2002","unstructured":"Koedel U, Scheld WM, Pfister HW: Pathogenesis and pathophysiology of pneumococcal meningitis. Lancet Infect Dis. 2002, 2: 721-736. 10.1016\/S1473-3099(02)00450-4.","journal-title":"Lancet Infect Dis"},{"key":"2599_CR4","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1097\/00005072-199903000-00006","volume":"58","author":"R Nau","year":"1999","unstructured":"Nau R, Soto A, Bruck W: Apoptosis of neurons in the dentate gyrus in humans suffering from bacterial meningitis. J Neuropathol Exp Neurol. 1999, 58: 265-274. 10.1097\/00005072-199903000-00006.","journal-title":"J Neuropathol Exp Neurol"},{"key":"2599_CR5","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1086\/317921","volume":"183","author":"JM Loeffler","year":"2001","unstructured":"Loeffler JM, Ringer R, Hablutzel M, Tauber MG, Leib SL: The free radical scavenger alpha-phenyl-tert-butyl nitrone aggravates hippocampal apoptosis and learning deficits in experimental pneumococcal meningitis. J Infect Dis. 2001, 183: 247-252. 10.1086\/317921.","journal-title":"J Infect Dis"},{"key":"2599_CR6","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.nbd.2006.07.014","volume":"24","author":"CL Bellac","year":"2006","unstructured":"Bellac CL, Coimbra RS, Christen S, Leib SL: Pneumococcal meningitis causes accumulation of neurotoxic kynurenine metabolites in brain regions prone to injury. Neurobiol Dis. 2006, 24: 395-402. 10.1016\/j.nbd.2006.07.014.","journal-title":"Neurobiol Dis"},{"key":"2599_CR7","doi-asserted-by":"publisher","first-page":"12884","DOI":"10.1523\/JNEUROSCI.4101-07.2007","volume":"27","author":"GJ Guillemin","year":"2007","unstructured":"Guillemin GJ, Cullen KM, Lim CK, Smythe GA, Garner B, Kapoor V, Takikawa O, Brew BJ: Characterization of the kynurenine pathway in human neurons. J Neurosci. 2007, 27: 12884-12892. 10.1523\/JNEUROSCI.4101-07.2007.","journal-title":"J Neurosci"},{"key":"2599_CR8","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/1471-2350-12-51","volume":"12","author":"FR de Souza","year":"2011","unstructured":"de Souza FR, Fontes FL, da Silva TA, Coutinho LG, Leib SL, Agnez-Lima LF: Association of kynurenine aminotransferase II gene C401T polymorphism with immune response in patients with meningitis. BMC Med Genet. 2011, 12: 51-","journal-title":"BMC Med Genet"},{"key":"2599_CR9","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1006\/nbdi.2000.0324","volume":"7","author":"HC Ha","year":"2000","unstructured":"Ha HC, Snyder SH: Poly(ADP-ribose) polymerase-1 in the nervous system. Neurobiol Dis. 2000, 7: 225-239. 10.1006\/nbdi.2000.0324.","journal-title":"Neurobiol Dis"},{"key":"2599_CR10","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1016\/0091-3057(95)00026-S","volume":"51","author":"JL van de Kamp","year":"1995","unstructured":"van de Kamp JL, Smolen A: Response of kynurenine pathway enzymes to pregnancy and dietary level of vitamin B-6. Pharmacol Biochem Behav. 1995, 51: 753-758. 10.1016\/0091-3057(95)00026-S.","journal-title":"Pharmacol Biochem Behav"},{"key":"2599_CR11","first-page":"25","volume":"25","author":"M Ashburner","year":"2000","unstructured":"Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, et al: Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000, 25: 25-29.","journal-title":"The Gene Ontology Consortium. Nat Genet"},{"key":"2599_CR12","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa M, Goto S: KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000, 28: 27-30. 10.1093\/nar\/28.1.27.","journal-title":"Nucleic Acids Res"},{"key":"2599_CR13","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1093\/brain\/124.9.1734","volume":"124","author":"SL Leib","year":"2001","unstructured":"Leib SL, Clements JM, Lindberg RL, Heimgartner C, Loeffler JM, Pfister LA, Tauber MG, Leppert D: Inhibition of matrix metalloproteinases and tumour necrosis factor alpha converting enzyme as adjuvant therapy in pneumococcal meningitis. Brain. 2001, 124: 1734-1742. 10.1093\/brain\/124.9.1734.","journal-title":"Brain"},{"key":"2599_CR14","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s00401-003-0672-7","volume":"105","author":"C Gianinazzi","year":"2003","unstructured":"Gianinazzi C, Grandgirard D, Imboden H, Egger L, Meli DN, Bifrare YD, Joss PC, Tauber MG, Borner C, Leib SL: Caspase-3 mediates hippocampal apoptosis in pneumococcal meningitis. Acta Neuropathol. 2003, 105: 499-507.","journal-title":"Acta Neuropathol"},{"key":"2599_CR15","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1203\/01.PDR.0000079185.67878.72","volume":"54","author":"SL Leib","year":"2003","unstructured":"Leib SL, Heimgartner C, Bifrare YD, Loeffler JM, Taauber MG: Dexamethasone aggravates hippocampal apoptosis and learning deficiency in pneumococcal meningitis in infant rats. Pediatr Res. 2003, 54: 353-357. 10.1203\/01.PDR.0000079185.67878.72.","journal-title":"Pediatr Res"},{"key":"2599_CR16","doi-asserted-by":"publisher","first-page":"R80","DOI":"10.1186\/gb-2004-5-10-r80","volume":"5","author":"RC Gentleman","year":"2004","unstructured":"Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, et al: Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 2004, 5: R80-10.1186\/gb-2004-5-10-r80.","journal-title":"Genome Biol"},{"key":"2599_CR17","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1093\/bioinformatics\/btg405","volume":"20","author":"L Gautier","year":"2004","unstructured":"Gautier L, Cope L, Bolstad BM, Irizarry RA: affy--analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 2004, 20: 307-315. 10.1093\/bioinformatics\/btg405.","journal-title":"Bioinformatics"},{"key":"2599_CR18","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1002\/sim.2109","volume":"24","author":"C Kooperberg","year":"2005","unstructured":"Kooperberg C, Aragaki A, Strand AD, Olson JM: Significance testing for small microarray experiments. Stat Med. 2005, 24: 2281-2298. 10.1002\/sim.2109.","journal-title":"Stat Med"},{"key":"2599_CR19","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/S0166-4328(01)00297-2","volume":"125","author":"Y Benjamini","year":"2001","unstructured":"Benjamini Y, Drai D, Elmer G, Kafkafi N, Golani I: Controlling the false discovery rate in behavior genetics research. Behav Brain Res. 2001, 125: 279-284. 10.1016\/S0166-4328(01)00297-2.","journal-title":"Behav Brain Res"},{"key":"2599_CR20","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.ab.2003.11.015","volume":"326","author":"KS Putt","year":"2004","unstructured":"Putt KS, Hergenrother PJ: An enzymatic assay for poly(ADP-ribose) polymerase-1 (PARP-1) via the chemical quantitation of NAD(+): application to the high-throughput screening of small molecules as potential inhibitors. Anal Biochem. 2004, 326: 78-86. 10.1016\/j.ab.2003.11.015.","journal-title":"Anal Biochem"},{"key":"2599_CR21","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1002\/hipo.10142","volume":"13","author":"YD Bifrare","year":"2003","unstructured":"Bifrare YD, Gianinazzi C, Imboden H, Leib SL, Tauber MG: Bacterial meningitis causes two distinct forms of cellular damage in the hippocampal dentate gyrus in infant rats. Hippocampus. 2003, 13: 481-488. 10.1002\/hipo.10142.","journal-title":"Hippocampus"},{"key":"2599_CR22","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/1741-7007-4-15","volume":"4","author":"RS Coimbra","year":"2006","unstructured":"Coimbra RS, Voisin V, de Saizieu AB, Lindberg RL, Wittwer M, Leppert D, Leib SL: Gene expression in cortex and hippocampus during acute pneumococcal meningitis. BMC Biol. 2006, 4: 15-10.1186\/1741-7007-4-15.","journal-title":"BMC Biol"},{"key":"2599_CR23","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1186\/1471-2334-10-176","volume":"10","author":"M Wittwer","year":"2010","unstructured":"Wittwer M, Grandgirard D, Rohrbach J, Leib SL: Tracking the transcriptional host response from the acute to the regenerative phase of experimental pneumococcal meningitis. BMC Infect Dis. 2010, 10: 176-10.1186\/1471-2334-10-176.","journal-title":"BMC Infect Dis"},{"key":"2599_CR24","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.neulet.2006.11.065","volume":"413","author":"S Ebert","year":"2007","unstructured":"Ebert S, Zeretzke M, Nau R, Michel U: Microglial cells and peritoneal macrophages release activin A upon stimulation with Toll-like receptor agonists. Neurosci Lett. 2007, 413: 241-244. 10.1016\/j.neulet.2006.11.065.","journal-title":"Neurosci Lett"},{"key":"2599_CR25","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1002\/jnr.22185","volume":"88","author":"H Wilms","year":"2010","unstructured":"Wilms H, Schwark T, Brandenburg LO, Sievers J, Dengler R, Deuschl G, Lucius R: Regulation of activin A synthesis in microglial cells: pathophysiological implications for bacterial meningitis. J Neurosci Res. 2010, 88: 16-23. 10.1002\/jnr.22185.","journal-title":"J Neurosci Res"},{"key":"2599_CR26","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.neuron.2006.07.012","volume":"51","author":"J Han","year":"2006","unstructured":"Han J, Mark MD, Li X, Xie M, Waka S, Rettig J, Herlitze S: RGS2 determines short-term synaptic plasticity in hippocampal neurons by regulating Gi\/o-mediated inhibition of presynaptic Ca2+ channels. Neuron. 2006, 51: 575-586. 10.1016\/j.neuron.2006.07.012.","journal-title":"Neuron"},{"key":"2599_CR27","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/S0306-4522(02)00260-9","volume":"114","author":"JM Taymans","year":"2002","unstructured":"Taymans JM, Wintmolders C, Te Riele P, Jurzak M, Groenewegen HJ, Leysen JE, Langlois X: Detailed localization of regulator of G protein signaling 2 messenger ribonucleic acid and protein in the rat brain. Neuroscience. 2002, 114: 39-53. 10.1016\/S0306-4522(02)00260-9.","journal-title":"Neuroscience"},{"key":"2599_CR28","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1016\/S0306-4522(99)00507-2","volume":"95","author":"H Ehrenreich","year":"2000","unstructured":"Ehrenreich H, Nau TR, Dembowski C, Hasselblatt M, Barth M, Hahn A, Schilling L, Siren AL, Bruck W: Endothelin b receptor deficiency is associated with an increased rate of neuronal apoptosis in the dentate gyrus. Neuroscience. 2000, 95: 993-1001.","journal-title":"Neuroscience"},{"key":"2599_CR29","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1111\/j.1432-1033.1995.414_2.x","volume":"233","author":"P Vigne","year":"1995","unstructured":"Vigne P, Feolde E, Van Renterghem C, Breittmayer JP, Frelin C: Properties and functions of a neuromedin-B-preferring bombesin receptor in brain microvascular endothelial cells. Eur J Biochem. 1995, 233: 414-418. 10.1111\/j.1432-1033.1995.414_2.x.","journal-title":"Eur J Biochem"},{"key":"2599_CR30","doi-asserted-by":"publisher","first-page":"4724","DOI":"10.4049\/jimmunol.170.9.4724","volume":"170","author":"PJ Zwijnenburg","year":"2003","unstructured":"Zwijnenburg PJ, van der Poll T, Florquin S, Roord JJ, Van Furth AM: IL-1 receptor type 1 gene-deficient mice demonstrate an impaired host defense against pneumococcal meningitis. J Immunol. 2003, 170: 4724-4730.","journal-title":"J Immunol"},{"key":"2599_CR31","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.4049\/jimmunol.158.4.1956","volume":"158","author":"KS Spanaus","year":"1997","unstructured":"Spanaus KS, Nadal D, Pfister HW, Seebach J, Widmer U, Frei K, Gloor S, Fontana A: C-X-C and C-C chemokines are expressed in the cerebrospinal fluid in bacterial meningitis and mediate chemotactic activity on peripheral blood-derived polymorphonuclear and mononuclear cells in vitro. J Immunol. 1997, 158: 1956-1964.","journal-title":"J Immunol"},{"key":"2599_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1086\/515079","volume":"28","author":"MG Tauber","year":"1999","unstructured":"Tauber MG, Moser B: Cytokines and chemokines in meningeal inflammation: biology and clinical implications. Clin Infect Dis. 1999, 28: 1-11. 10.1086\/515079. quiz 12","journal-title":"Clin Infect Dis"},{"key":"2599_CR33","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.neulet.2003.11.024","volume":"355","author":"JF Ji","year":"2004","unstructured":"Ji JF, He BP, Dheen ST, Tay SS: Expression of chemokine receptors CXCR4, CCR2, CCR5 and CX3CR1 in neural progenitor cells isolated from the subventricular zone of the adult rat brain. Neurosci Lett. 2004, 355: 236-240. 10.1016\/j.neulet.2003.11.024.","journal-title":"Neurosci Lett"},{"key":"2599_CR34","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1002\/cne.20729","volume":"492","author":"G Banisadr","year":"2005","unstructured":"Banisadr G, Gosselin RD, Mechighel P, Rostene W, Kitabgi P, Melik Parsadaniantz S: Constitutive neuronal expression of CCR2 chemokine receptor and its colocalization with neurotransmitters in normal rat brain: functional effect of MCP-1\/CCL2 on calcium mobilization in primary cultured neurons. J Comp Neurol. 2005, 492: 178-192. 10.1002\/cne.20729.","journal-title":"J Comp Neurol"},{"key":"2599_CR35","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1002\/glia.10357","volume":"46","author":"WH Shin","year":"2004","unstructured":"Shin WH, Lee DY, Park KW, Kim SU, Yang MS, Joe EH, Jin BK: Microglia expressing interleukin-13 undergo cell death and contribute to neuronal survival in vivo. Glia. 2004, 46: 142-152. 10.1002\/glia.10357.","journal-title":"Glia"},{"key":"2599_CR36","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1002\/glia.10057","volume":"38","author":"MS Yang","year":"2002","unstructured":"Yang MS, Park EJ, Sohn S, Kwon HJ, Shin WH, Pyo HK, Jin B, Choi KS, Jou I, Joe EH: Interleukin-13 and \u22124 induce death of activated microglia. Glia. 2002, 38: 273-280. 10.1002\/glia.10057.","journal-title":"Glia"},{"key":"2599_CR37","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1097\/00019052-199706000-00015","volume":"10","author":"HW Pfister","year":"1997","unstructured":"Pfister HW, Scheld WM: Brain injury in bacterial meningitis: therapeutic implications. Curr Opin Neurol. 1997, 10: 254-259. 10.1097\/00019052-199706000-00015.","journal-title":"Curr Opin Neurol"},{"key":"2599_CR38","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1038\/ejcn.2010.107","volume":"64","author":"SC Huang","year":"2010","unstructured":"Huang SC, Wei JC, Wu DJ, Huang YC: Vitamin B(6) supplementation improves pro-inflammatory responses in patients with rheumatoid arthritis. Eur J Clin Nutr. 2010, 64: 1007-1013. 10.1038\/ejcn.2010.107.","journal-title":"Eur J Clin Nutr"},{"key":"2599_CR39","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.3945\/ajcn.111.029751","volume":"95","author":"A Ulvik","year":"2012","unstructured":"Ulvik A, Midttun O, Ringdal Pedersen E, Nygard O, Ueland PM: Association of plasma B-6 vitamers with systemic markers of inflammation before and after pyridoxine treatment in patients with stable angina pectoris. Am J Clin Nutr. 2012, 95: 1072-1078. 10.3945\/ajcn.111.029751.","journal-title":"Am J Clin Nutr"},{"key":"2599_CR40","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1017\/S0007114511000407","volume":"106","author":"V Lotto","year":"2011","unstructured":"Lotto V, Choi SW, Friso S: Vitamin B6: a challenging link between nutrition and inflammation in CVD. Br J Nutr. 2011, 106: 183-195. 10.1017\/S0007114511000407.","journal-title":"Br J Nutr"},{"key":"2599_CR41","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1096\/fj.04-2665fje","volume":"19","author":"TG Granda","year":"2005","unstructured":"Granda TG, Liu XH, Smaaland R, Cermakian N, Filipski E, Sassone-Corsi P, Levi F: Circadian regulation of cell cycle and apoptosis proteins in mouse bone marrow and tumor. FASEB J. 2005, 19: 304-306.","journal-title":"FASEB J"},{"key":"2599_CR42","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1172\/JCI105785","volume":"47","author":"MI Rapoport","year":"1968","unstructured":"Rapoport MI, Beisel WR: Circadian periodicity of tryptophan metabolism. J Clin Invest. 1968, 47: 934-939. 10.1172\/JCI105785.","journal-title":"J Clin Invest"},{"key":"2599_CR43","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1530\/eje.0.1390089","volume":"139","author":"A Munoz-Hoyos","year":"1998","unstructured":"Munoz-Hoyos A, Molina-Carballo A, Macias M, Rodriguez-Cabezas T, Martin-Medina E, Narbona-Lopez E, Valenzuela-Ruiz A, Acuna-Castroviejo D: Comparison between tryptophan methoxyindole and kynurenine metabolic pathways in normal and preterm neonates and in neonates with acute fetal distress. Eur J Endocrinol. 1998, 139: 89-95.","journal-title":"Eur J Endocrinol"},{"key":"2599_CR44","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1046\/j.1365-2265.1997.2991136.x","volume":"47","author":"A Munoz-Hoyos","year":"1997","unstructured":"Munoz-Hoyos A, Molina-Carballo A, Rodriguez-Cabezas T, Uberos-Fernandez J, Ruiz-Cosano C, Acuna-Castroviejo D: Relationships between methoxyindole and kynurenine pathway metabolites in plasma and urine in children suffering from febrile and epileptic seizures. Clin Endocrinol (Oxf). 1997, 47: 667-677. 10.1046\/j.1365-2265.1997.2991136.x.","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2599_CR45","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1002\/jnr.21055","volume":"84","author":"A Spreer","year":"2006","unstructured":"Spreer A, Gerber J, Baake D, Hanssen M, Huether G, Nau R: Antiinflammatory but no neuroprotective effects of melatonin under clinical treatment conditions in rabbit models of bacterial meningitis. J Neurosci Res. 2006, 84: 1575-1579. 10.1002\/jnr.21055.","journal-title":"J Neurosci Res"},{"key":"2599_CR46","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1111\/j.1749-6632.2012.06649.x","volume":"1264","author":"S Masri","year":"2012","unstructured":"Masri S, Zocchi L, Katada S, Mora E, Sassone-Corsi P: The circadian clock transcriptional complex: metabolic feedback intersects with epigenetic control. Ann N Y Acad Sci. 2012, 1264: 103-109. 10.1111\/j.1749-6632.2012.06649.x.","journal-title":"Ann N Y Acad Sci"},{"key":"2599_CR47","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1126\/science.1170803","volume":"324","author":"Y Nakahata","year":"2009","unstructured":"Nakahata Y, Sahar S, Astarita G, Kaluzova M, Sassone-Corsi P: Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science. 2009, 324: 654-657. 10.1126\/science.1170803.","journal-title":"Science"},{"key":"2599_CR48","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1126\/science.1171641","volume":"324","author":"KM Ramsey","year":"2009","unstructured":"Ramsey KM, Yoshino J, Brace CS, Abrassart D, Kobayashi Y, Marcheva B, Hong HK, Chong JL, Buhr ED, Lee C, et al: Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science. 2009, 324: 651-654. 10.1126\/science.1171641.","journal-title":"Science"},{"key":"2599_CR49","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.brainresbull.2008.02.013","volume":"76","author":"LA Craig","year":"2008","unstructured":"Craig LA, McDonald RJ: Chronic disruption of circadian rhythms impairs hippocampal memory in the rat. Brain Res Bull. 2008, 76: 141-151. 10.1016\/j.brainresbull.2008.02.013.","journal-title":"Brain Res Bull"},{"key":"2599_CR50","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1111\/j.1741-4520.2006.00107.x","volume":"46","author":"H Sei","year":"2006","unstructured":"Sei H, Oishi K, Sano A, Seno H, Ohmori T, Morita Y, Ishida N: Clock mutant mice with Jcl\/ICR background shows an impaired learning ability in water maze, but not in passive avoidance, at the beginning of dark phase. Congenit Anom (Kyoto). 2006, 46: 81-85. 10.1111\/j.1741-4520.2006.00107.x.","journal-title":"Congenit Anom (Kyoto)"},{"key":"2599_CR51","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1159\/000096218","volume":"29","author":"D Grandgirard","year":"2007","unstructured":"Grandgirard D, Bifrare YD, Pleasure SJ, Kummer J, Leib SL, Tauber MG: Pneumococcal meningitis induces apoptosis in recently postmitotic immature neurons in the dentate gyrus of neonatal rats. Dev Neurosci. 2007, 29: 134-142. 10.1159\/000096218.","journal-title":"Dev Neurosci"},{"key":"2599_CR52","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1086\/426399","volume":"191","author":"YD Bifrare","year":"2005","unstructured":"Bifrare YD, Kummer J, Joss P, Tauber MG, Leib SL: Brain-derived neurotrophic factor protects against multiple forms of brain injury in bacterial meningitis. J Infect Dis. 2005, 191: 40-45. 10.1086\/426399.","journal-title":"J Infect Dis"},{"key":"2599_CR53","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.ejphar.2006.10.029","volume":"555","author":"MH Larsen","year":"2007","unstructured":"Larsen MH, Rosenbrock H, Sams-Dodd F, Mikkelsen JD: Expression of brain derived neurotrophic factor, activity-regulated cytoskeleton protein mRNA, and enhancement of adult hippocampal neurogenesis in rats after sub-chronic and chronic treatment with the triple monoamine re-uptake inhibitor tesofensine. Eur J Pharmacol. 2007, 555: 115-121. 10.1016\/j.ejphar.2006.10.029.","journal-title":"Eur J Pharmacol"},{"key":"2599_CR54","doi-asserted-by":"publisher","first-page":"2172","DOI":"10.1038\/sj.onc.1206222","volume":"22","author":"M Unoki","year":"2003","unstructured":"Unoki M, Nakamura Y: EGR2 induces apoptosis in various cancer cell lines by direct transactivation of BNIP3L and BAK. Oncogene. 2003, 22: 2172-2185. 10.1038\/sj.onc.1206222.","journal-title":"Oncogene"},{"key":"2599_CR55","doi-asserted-by":"publisher","first-page":"e002","DOI":"10.1621\/nrs.04002","volume":"4","author":"MA Maxwell","year":"2006","unstructured":"Maxwell MA, Muscat GE: The NR4A subgroup: immediate early response genes with pleiotropic physiological roles. Nucl Recept Signal. 2006, 4: e002-","journal-title":"Nucl Recept Signal"},{"key":"2599_CR56","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1210\/me.2005-0331","volume":"20","author":"L Pei","year":"2006","unstructured":"Pei L, Castrillo A, Tontonoz P: Regulation of macrophage inflammatory gene expression by the orphan nuclear receptor Nur77. Mol Endocrinol. 2006, 20: 786-794.","journal-title":"Mol Endocrinol"},{"issue":"Suppl","key":"2599_CR57","doi-asserted-by":"crossref","first-page":"S255","DOI":"10.1194\/jlr.R800024-JLR200","volume":"50","author":"TM McIntyre","year":"2009","unstructured":"McIntyre TM, Prescott SM, Stafforini DM: The emerging roles of PAF acetylhydrolase. J Lipid Res. 2009, 50 (Suppl): S255-S259.","journal-title":"J Lipid Res"},{"key":"2599_CR58","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1161\/01.STR.0000257981.09329.d2","volume":"38","author":"K Umemura","year":"2007","unstructured":"Umemura K, Kato I, Hirashima Y, Ishii Y, Inoue T, Aoki J, Kono N, Oya T, Hayashi N, Hamada H, et al: Neuroprotective role of transgenic PAF-acetylhydrolase II in mouse models of focal cerebral ischemia. Stroke. 2007, 38: 1063-1068. 10.1161\/01.STR.0000257981.09329.d2.","journal-title":"Stroke"},{"key":"2599_CR59","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1086\/313922","volume":"31","author":"D Leppert","year":"2000","unstructured":"Leppert D, Leib SL, Grygar C, Miller KM, Schaad UB, Hollander GA: Matrix metalloproteinase (MMP)-8 and MMP-9 in cerebrospinal fluid during bacterial meningitis: association with blood\u2013brain barrier damage and neurological sequelae. Clin Infect Dis. 2000, 31: 80-84. 10.1086\/313922.","journal-title":"Clin Infect Dis"},{"key":"2599_CR60","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1097\/NEN.0b013e31818b4801","volume":"67","author":"LO Brandenburg","year":"2008","unstructured":"Brandenburg LO, Varoga D, Nicolaeva N, Leib SL, Wilms H, Podschun R, Wruck CJ, Schroder JM, Pufe T, Lucius R: Role of glial cells in the functional expression of LL-37\/rat cathelin-related antimicrobial peptide in meningitis. J Neuropathol Exp Neurol. 2008, 67: 1041-1054. 10.1097\/NEN.0b013e31818b4801.","journal-title":"J Neuropathol Exp Neurol"},{"key":"2599_CR61","doi-asserted-by":"publisher","first-page":"E824","DOI":"10.1152\/ajpendo.00349.2005","volume":"290","author":"H Liu","year":"2006","unstructured":"Liu H, Zheng F, Cao Q, Ren B, Zhu L, Striker G, Vlassara H: Amelioration of oxidant stress by the defensin lysozyme. Am J Physiol Endocrinol Metab. 2006, 290: E824-E832. 10.1152\/ajpendo.00349.2005.","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2599_CR62","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1111\/j.1471-4159.2005.03033.x","volume":"93","author":"B Viviani","year":"2005","unstructured":"Viviani B, Bartesaghi S, Corsini E, Villa P, Ghezzi P, Garau A, Galli CL, Marinovich M: Erythropoietin protects primary hippocampal neurons increasing the expression of brain-derived neurotrophic factor. J Neurochem. 2005, 93: 412-421. 10.1111\/j.1471-4159.2005.03033.x.","journal-title":"J Neurochem"},{"key":"2599_CR63","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/infdis\/173.1.166","volume":"173","author":"SL Leib","year":"1996","unstructured":"Leib SL, Kim YS, Ferriero DM, Tauber MG: Neuroprotective effect of excitatory amino acid antagonist kynurenic acid in experimental bacterial meningitis. J Infect Dis. 1996, 173: 166-171. 10.1093\/infdis\/173.1.166.","journal-title":"J Infect Dis"},{"key":"2599_CR64","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1196\/annals.1418.005","volume":"1144","author":"MP Mattson","year":"2008","unstructured":"Mattson MP: Glutamate and neurotrophic factors in neuronal plasticity and disease. Ann N Y Acad Sci. 2008, 1144: 97-112. 10.1196\/annals.1418.005.","journal-title":"Ann N Y Acad Sci"},{"key":"2599_CR65","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1124\/jpet.109.155176","volume":"331","author":"TT Yang","year":"2009","unstructured":"Yang TT, Wang SJ: Pyridoxine inhibits depolarization-evoked glutamate release in nerve terminals from rat cerebral cortex: a possible neuroprotective mechanism?. J Pharmacol Exp Ther. 2009, 331: 244-254. 10.1124\/jpet.109.155176.","journal-title":"J Pharmacol Exp Ther"},{"key":"2599_CR66","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1177\/088307380301801202","volume":"18","author":"L Li","year":"2003","unstructured":"Li L, Shui QX, Zhao ZY: Regulation of brain-derived neurotrophic factor (BDNF) expression following antibiotic treatment of experimental bacterial meningitis. J Child Neurol. 2003, 18: 828-834. 10.1177\/088307380301801202.","journal-title":"J Child Neurol"}],"container-title":["BMC Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2334-13-393.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1471-2334-13-393\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2334-13-393","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2334-13-393.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T03:42:41Z","timestamp":1688442161000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/1471-2334-13-393"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,8,27]]},"references-count":66,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["2599"],"URL":"https:\/\/doi.org\/10.1186\/1471-2334-13-393","relation":{},"ISSN":["1471-2334"],"issn-type":[{"value":"1471-2334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,8,27]]},"assertion":[{"value":"23 January 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 August 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 August 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"393"}}