{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:27:20Z","timestamp":1787772440009,"version":"build-2784847793"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Inflammation is one of the effective factors, in the development of functional disorders of the nervous system. Pentoxifylline (PTX) has an inhibitory effect on inflammatory factors. Therefore the aim of this study was to evaluate the effect of PTX on learning, memory and expression of genes, involved in neuronal survival in the rat hippocampus, following systemic lipopolysaccharide (LPS) injection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Male rats were randomly divided into 5 groups of control, LPS and LPS + PTX, receiving doses of 10, 25 and 50 mg\/kg of PTX, respectively. In LPS groups, LPS was injected (5 mg\/kg; intraperitoneal), and after one week, rats received intraperitoneal PTX for 14 days, in the treatment groups. Learning and memory were evaluated by object location task (OLT) and novel object recognition (NOR). Then, the hippocampus was dissected in order to measure the expression of the associated genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The results showed that peripheral LPS injection caused significant damage (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.01) to learning and memory with respect to controls, but PTX with doses of 10 and 50 mg\/kg prevented these impairments. Results from reverse transcription polymerase chain reaction (RT-PCR) showed that LPS significantly increased the expression of\n                      <jats:italic toggle=\"yes\">Bax<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">TNF- \u03b1<\/jats:italic>\n                      with respect to controls. PTX in the LPS + PTX group significantly increased the expression of\n                      <jats:italic toggle=\"yes\">Bcl-2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">BAD<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Caspase-3<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      Other than the increased\n                      <jats:italic toggle=\"yes\">Bcl-2<\/jats:italic>\n                      expression, PTX had no significant effect on the expression of other genes, therefore further studies are needed to find out how PTX improves the learning and memory impairments, following the peripheral inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/ijpvm.ijpvm_170_19","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T08:42:26Z","timestamp":1716885746000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":8,"title":["Effect of Pentoxifylline on Apoptotic-Related Gene Expression Profile, Learning and Memory Impairment Induced by Systemic Lipopolysaccharide Administration in the Rat Hippocampus"],"prefix":"10.4103","volume":"11","author":[{"given":"Zahra","family":"Akbari","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran"},{"name":"International Campuses, Tehran University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parham","family":"Reisi","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anahita","family":"Torkaman-Boutorabi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Farahmandfar","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran"},{"name":"Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"R1-20250812","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/imm.12922","article-title":"Inflammation in CNS neurodegenerative diseases","volume":"154","author":"Stephenson","year":"2018","journal-title":"Immunology"},{"key":"R2-20250812","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1159\/000330247","article-title":"Neuroinflammation: A common pathway in CNS diseases as mediated at the blood-brain barrier","volume":"19","author":"Erickson","year":"2012","journal-title":"Neuroimmunomodulation"},{"key":"R3-20250812","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1152\/physrev.00050.2017","article-title":"Blood-brain barrier: From physiology to disease and back","volume":"99","author":"Sweeney","year":"2018","journal-title":"Physiol Rev"},{"key":"R4-20250812","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.bbi.2010.10.015","article-title":"Immune modulation of learning, memory, neural plasticity and neurogenesis","volume":"25","author":"Yirmiya","year":"2011","journal-title":"Brain Behav Immun"},{"key":"R5-20250812","doi-asserted-by":"crossref","first-page":"731","DOI":"10.4236\/abb.2012.326094","article-title":"Pentoxifylline suppressed LPS-induced inflammatory and apoptotic signaling in neuronal cells","volume":"3","author":"Muchhala","year":"2012","journal-title":"Adv Biosci Biotechnol"},{"key":"R6-20250812","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1590\/S1807-59322008000300006","article-title":"Insights into the regulation of TNF-a production in human mononuclear cells: The effects of non-specific phosphodiesterase inhibition","volume":"63","author":"Deree","year":"2008","journal-title":"Clinics"},{"key":"R7-20250812","first-page":"1083","article-title":"Effect of pentoxifylline on ischemia-induced brain damage and spatial memory impairment in rat","volume":"15","author":"Movassaghi","year":"2012","journal-title":"Iran J Basic Med Sci"},{"key":"R8-20250812","first-page":"108179","article-title":"Pentoxifylline neuroprotective effects are possibly related to its anti-inflammatory and TNF-alpha inhibitory properties, in the 6-OHDA model of Parkinson's disease","author":"Neves","year":"2015","journal-title":"Parkinson'sDis 2015"},{"key":"R9-20250812","first-page":"93","article-title":"Effects of different doses of pentoxifylline on CA1 pyramidal cells of hippocampus following brain ischemia in rats","volume":"13","author":"Movassaghi","year":"2011","journal-title":"Adv Cogn Sci"},{"key":"R10-20250812","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S0091-3057(00)00279-3","article-title":"Pentoxifylline improves learning and memory in glutamate-lesioned rats","volume":"66","author":"Cunha","year":"2000","journal-title":"Pharmacol Biochem Behav"},{"key":"R11-20250812","doi-asserted-by":"crossref","first-page":"3823","DOI":"10.1182\/blood.V95.12.3823.012k07_3823_3831","article-title":"LPS induces apoptosis in macrophages mostly through the autocrine production of TNF-\u03b1","volume":"95","author":"Xaus","year":"2000","journal-title":"Blood"},{"key":"R12-20250812","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10059-010-0105-0","article-title":"Reactive oxygen species in TNF\u03b1-induced signaling and cell death","volume":"30","author":"Morgan","year":"2010","journal-title":"Mol Cells"},{"key":"R13-20250812","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1634\/theoncologist.11-4-397","article-title":"TNF-\u03b1 in cancer treatment: Molecular insights, antitumor effects, and clinical utility","volume":"11","author":"van Horssen","year":"2006","journal-title":"Oncologist"},{"key":"R14-20250812","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.cbpa.2017.06.014","article-title":"Progress in targeting the BCL-2 family of proteins","volume":"39","author":"Garner","year":"2017","journal-title":"Curr Opin Chem Biol"},{"key":"R15-20250812","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1038\/cdd.2017.22","article-title":"Non-apoptotic functions of BCL-2 family proteins","volume":"24","author":"Gross","year":"2017","journal-title":"Cell Death Differ"},{"key":"R16-20250812","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/cdd.2017.170","article-title":"Anti-apoptotic BCL-2 family members in development","volume":"25","author":"Opferman","year":"2018","journal-title":"Cell Death Differ"},{"key":"R17-20250812","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nrm2308","article-title":"The BCL-2 protein family: Opposing activities that mediate cell death","volume":"9","author":"Youle","year":"2008","journal-title":"Nat Rev Mol Cell Biol"},{"key":"R18-20250812","first-page":"8881","article-title":"Low molecular weight heparin prevents lipopolysaccharide induced-hippocampus-dependent cognitive impairments in mice","volume":"8","author":"Li","year":"2015","journal-title":"Int J Clin Exp Pathol"},{"key":"R19-20250812","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.pathophys.2009.03.003","article-title":"Determination of the extracellular basal levels of glutamate and GABA at dentate gyrus of streptozotocin-induced diabetic rats","volume":"16","author":"Reisi","year":"2009","journal-title":"Pathophysiology"},{"key":"R20-20250812","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.beproc.2009.10.003","article-title":"Object familiarization and novel-object preference in rats","volume":"83","author":"Gaskin","year":"2010","journal-title":"Behav Processes"},{"key":"R21-20250812","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jneumeth.2008.02.006","article-title":"Automated scoring of novel object recognition in rats","volume":"171","author":"Rutten","year":"2008","journal-title":"J Neurosci Methods"},{"key":"R22-20250812","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s10339-011-0430-z","article-title":"The novel object recognition memory: Neurobiology, test procedure, and its modifications","volume":"13","author":"Antunes","year":"2012","journal-title":"Cogn Process"},{"key":"R23-20250812","doi-asserted-by":"crossref","first-page":"15","DOI":"10.4103\/1735-5362.199042","article-title":"Effects of doxepin on gene expressions of Bcl-2 family, TNF-\u03b1, MAP kinase 14, and Akt1 in the hippocampus of rats exposed to stress","volume":"12","author":"Reisi","year":"2017","journal-title":"Res Pharm Sci"},{"key":"R24-20250812","doi-asserted-by":"crossref","first-page":"F1164","DOI":"10.1152\/ajprenal.00437.2003","article-title":"Effect of thiazide on renal gene expression of apical calcium channels and calbindins","volume":"287","author":"Lee","year":"2004","journal-title":"Am J Physiol Renal Physiol"},{"key":"R25-20250812","doi-asserted-by":"crossref","first-page":"F230","DOI":"10.1152\/ajprenal.00057.2015","article-title":"The role of calbindin-D28k on renal calcium and magnesium handling during treatment with loop and thiazide diuretics","volume":"310","author":"Lee","year":"2015","journal-title":"Am J Physiol Renal Physiol"},{"key":"R26-20250812","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/nrn3880","article-title":"Immune attack: The role of inflammation in Alzheimer disease","volume":"16","author":"Heppner","year":"2015","journal-title":"Nat Rev Neurosci"},{"key":"R27-20250812","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","article-title":"Neuroinflammation in Alzheimer's disease","volume":"14","author":"Heneka","year":"2015","journal-title":"Lancet Neurol"},{"key":"R28-20250812","first-page":"575","article-title":"Inflammation as a central mechanism in Alzheimer's disease","volume":"4","author":"Kinney","year":"2018","journal-title":"Alzheimers Dement"},{"key":"R29-20250812","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.plipres.2009.06.002","article-title":"Lipopolysaccharide: Biosynthetic pathway and structure modification","volume":"49","author":"Wang","year":"2010","journal-title":"Prog Lipid Res"},{"key":"R30-20250812","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0169-328X(94)90197-X","article-title":"Peripheral administration of lipopolysaccharide induces the expression of cytokine transcripts in the brain and pituitary of mice","volume":"27","author":"Lay\u00e9","year":"1994","journal-title":"Brain Res Mol Brain Res"},{"key":"R31-20250812","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1038\/jcbfm.2011.197","article-title":"Neurological diseases in relation to the blood\u2013brain barrier","volume":"32","author":"Rosenberg","year":"2012","journal-title":"J Cereb Blood Flow Metab"},{"key":"R32-20250812","doi-asserted-by":"crossref","first-page":"409321","DOI":"10.1155\/2013\/409321","article-title":"Anti-inflammatory effect of procyanidins from wild grape (Vitis amurensis) seeds in LPS-induced RAW 264.7 cells","volume":"2013","author":"Bak","year":"2013","journal-title":"Oxid Med Cell Longev"},{"key":"R33-20250812","doi-asserted-by":"crossref","first-page":"72","DOI":"10.3389\/fcell.2016.00072","article-title":"Microglia ontology and signaling","volume":"4","author":"ElAli","year":"2016","journal-title":"Front Cell Dev Biol"},{"key":"R34-20250812","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.neuint.2013.04.007","article-title":"Microglia are the major source of TNF-\u03b1 and TGF-\u03b21 in postnatal glial cultures; regulation by cytokines, lipopolysaccharide, and vitronectin","volume":"63","author":"Welser-Alves","year":"2013","journal-title":"Neurochem Int"},{"key":"R35-20250812","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2008.03.036","article-title":"TNF-\u03b1 induces two distinct caspase-8 activation pathways","volume":"133","author":"Wang","year":"2008","journal-title":"Cell"},{"key":"R36-20250812","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1016\/j.bbamcr.2016.09.012","article-title":"Activation of apoptosis signalling pathways by reactive oxygen species","volume":"1863","author":"Redza-Dutordoir","year":"2016","journal-title":"Biochim Biophys Acta"},{"key":"R37-20250812","doi-asserted-by":"crossref","first-page":"39","DOI":"10.4103\/abr.abr_33_19","article-title":"The effect of pentoxifylline on passive avoidance learning and expression of tumor necrosis factor-alpha and caspase-3 in the rat hippocampus following lipopolysaccharide-induced inflammation","volume":"8","author":"Akbari","year":"2019","journal-title":"Adv Biomed Res"},{"key":"R38-20250812","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1016\/j.drudis.2014.06.029","article-title":"Targeting TNF: A therapeutic strategy for Alzheimer's disease","volume":"19","author":"Cheng","year":"2014","journal-title":"Drug Discov Today"},{"key":"R39-20250812","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1038\/sj.cdd.4400439","article-title":"Growth factors prevent changes in Bcl-2 and Bax expression and neuronal apoptosis induced by nitric oxide","volume":"5","author":"Tamatani","year":"1998","journal-title":"Cell Death Differ"},{"key":"R40-20250812","doi-asserted-by":"crossref","first-page":"110","DOI":"10.4103\/abr.abr_49_17","article-title":"The effects of pentoxifylline on serum levels of interleukin 10 and interferon gamma and memory function in lipopolysaccharide-induced inflammation in rats","volume":"6","author":"Dolatabadi","year":"2017","journal-title":"Adv Biomed Res"},{"key":"R41-20250812","doi-asserted-by":"crossref","first-page":"883","DOI":"10.15252\/msb.20167144","article-title":"Gene-specific correlation of RNA and protein levels in human cells and tissues","volume":"12","author":"Edfors","year":"2016","journal-title":"Mol Syst Biol"},{"key":"R42-20250812","doi-asserted-by":"crossref","first-page":"a008722","DOI":"10.1101\/cshperspect.a008722","article-title":"Multiple functions of BCL-2 family proteins","volume":"5","author":"Hardwick","year":"2013","journal-title":"Cold Spring Harb Perspect Biol"}],"container-title":["International Journal of Preventive Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/ijpvm.IJPVM_170_19","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T18:46:59Z","timestamp":1787770019000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/ijpvm.IJPVM_170_19"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020]]}},"URL":"https:\/\/doi.org\/10.4103\/ijpvm.ijpvm_170_19","relation":{},"ISSN":["2008-7802","2008-8213"],"issn-type":[{"value":"2008-7802","type":"print"},{"value":"2008-8213","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1]]},"assertion":[{"value":"2019-05-06","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-29","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}