{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:12:45Z","timestamp":1789557165795,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T00:00:00Z","timestamp":1617926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2019R1A6A1A11036849"],"award-info":[{"award-number":["NRF-2019R1A6A1A11036849"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2020R1F1A1071973"],"award-info":[{"award-number":["NRF-2020R1F1A1071973"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2020R1F1A1052380"],"award-info":[{"award-number":["NRF-2020R1F1A1052380"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Angelica gigas Nakai root contains decursin which exerts beneficial properties such as anti-amnesic and anti-inflammatory activities. Until now, however, the neuroprotective effects of decursin against transient ischemic injury in the forebrain have been insufficiently investigated. Here, we revealed that post-treatment with decursin and the root extract saved pyramidal neurons in the hippocampus following transient ischemia for 5 min in gerbil forebrain. Through high-performance liquid chromatography, we defined that decursin was contained in the extract as 7.3 \u00b1 0.2%. Based on this, we post-treated with 350 mg\/kg of extract, which is the corresponding dosage of 25 mg\/kg of decursin that exerted neuroprotection in gerbil hippocampus against the ischemia. In addition, behavioral tests were conducted to evaluate ischemia-induced dysfunctions via tests of spatial memory (by the 8-arm radial maze test) and learning memory (by the passive avoidance test), and post-treatment with the extract and decursin attenuated ischemia-induced memory impairments. Furthermore, we carried out histochemistry, immunohistochemistry, and double immunohistofluorescence. Pyramidal neurons located in the subfield cornu ammonis 1 (CA1) among the hippocampal subfields were dead at 5 days after the ischemia; however, treatment with the extract and decursin saved the pyramidal neurons after ischemia. Immunoglobulin G (IgG, an indicator of extravasation), which is not found in the parenchyma in normal brain tissue, was apparently shown in CA1 parenchyma from 2 days after the ischemia, but IgG leakage was dramatically attenuated in the CA1 parenchyma treated with the extract and decursin. Furthermore, astrocyte endfeet, which are a component of the blood\u2013brain barrier (BBB), were severely damaged at 5 days after the ischemia; however, post-treatment with the extract and decursin dramatically attenuated the damage of the endfeet. In brief, therapeutic treatment of the extract of Angelica gigas Nakai root and decursin after 5 min transient forebrain ischemia protected hippocampal neurons from the ischemia, showing that ischemia-induced BBB leakage and damage of astrocyte endfeet was significantly attenuated by the extract and decursin. Based on these findings, we suggest that Angelica gigas Nakai root containing decursin can be employed as a pharmaceutical composition to develop a therapeutic strategy for brain ischemic injury.<\/jats:p>","DOI":"10.3390\/molecules26082161","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T05:52:00Z","timestamp":1618206720000},"page":"2161","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Therapeutic Effects of Decursin and Angelica gigas Nakai Root Extract in Gerbil Brain after Transient Ischemia via Protecting BBB Leakage and Astrocyte Endfeet Damage"],"prefix":"10.3390","volume":"26","author":[{"given":"Tae-Kyeong","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0314-5195","authenticated-orcid":false,"given":"II-Jun","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyejin","family":"Sim","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Chul","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Hyeon","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, Korea"},{"name":"Department of Physical Therapy, College of Health Science, Youngsan University, Yangsan 50510, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8785-4508","authenticated-orcid":false,"given":"Dae-Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangnung-Wonju National University, Gangneung 25457, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon-Ha","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Korean Medicine, Dongguk University, Gyeongju 38066, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5508-9004","authenticated-orcid":false,"given":"Choong-Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 31116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Dai","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Food Biotechnology, School of Biotechnology, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7178-6501","authenticated-orcid":false,"given":"Moo-Ho","family":"Won","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Young","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1161\/STROKEAHA.108.192218","article-title":"Definition and evaluation of transient ischemic attack: A scientific statement for healthcare professionals from the american heart association\/american stroke association stroke council; council on cardiovascular surgery and anesthesia; council on cardiovascular radiology and intervention; council on cardiovascular nursing; and the interdisciplinary council on peripheral vascular disease. The American academy of neurology affirms the value of this statement as an educational tool for neurologists","volume":"40","author":"Easton","year":"2009","journal-title":"Stroke"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/BF00691853","article-title":"Selective vulnerability in the gerbil hippocampus following transient ischemia","volume":"62","author":"Kirino","year":"1984","journal-title":"Acta Neuropathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.brainres.2013.03.008","article-title":"Neuronal damage and gliosis in the somatosensory cortex induced by various durations of transient cerebral ischemia in gerbils","volume":"1510","author":"Lee","year":"2013","journal-title":"Brain Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.4103\/1673-5374.253524","article-title":"Time-course pattern of neuronal loss and gliosis in gerbil hippocampi following mild, severe, or lethal transient global cerebral ischemia","volume":"14","author":"Lee","year":"2019","journal-title":"Neural Regen. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s11011-018-0192-8","article-title":"Neuronal loss and gliosis in the rat striatum subjected to 15 and 30 minutes of middle cerebral artery occlusion","volume":"33","author":"Park","year":"2018","journal-title":"Metab. Brain Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0006-8993(82)90833-2","article-title":"Delayed neuronal death in the gerbil hippocampus following ischemia","volume":"239","author":"Kirino","year":"1982","journal-title":"Brain Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.exger.2018.01.015","article-title":"Long-term treadmill exercise improves memory impairment through restoration of decreased synaptic adhesion molecule 1\/2\/3 induced by transient cerebral ischemia in the aged gerbil hippocampus","volume":"103","author":"Ahn","year":"2018","journal-title":"Exp. Gerontol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lee, T.K., Kang, I.J., Kim, B., Sim, H.J., Kim, D.W., Ahn, J.H., Lee, J.C., Ryoo, S., Shin, M.C., and Cho, J.H. (2020). Experimental pretreatment with chlorogenic acid prevents transient ischemia-induced cognitive decline and neuronal damage in the hippocampus through anti-oxidative and anti-inflammatory effects. Molecules, 25.","DOI":"10.3390\/molecules25163578"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.expneurol.2008.11.022","article-title":"Timp-3 and mmp-3 contribute to delayed inflammation and hippocampal neuronal death following global ischemia","volume":"216","author":"Walker","year":"2009","journal-title":"Exp. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.pneurobio.2013.11.006","article-title":"Excitotoxicity and stroke: Identifying novel targets for neuroprotection","volume":"115","author":"Lai","year":"2014","journal-title":"Prog. Neurobiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"149","DOI":"10.5115\/acb.2014.47.3.149","article-title":"Neuroprotection of antioxidant enzymes against transient global cerebral ischemia in gerbils","volume":"47","author":"Lee","year":"2014","journal-title":"Anat. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"158","DOI":"10.2174\/1567202614666170328094042","article-title":"Atomoxetine protects against nmda receptor-mediated hippocampal neuronal death following transient global cerebral ischemia","volume":"14","author":"Park","year":"2017","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"C343","DOI":"10.1152\/ajpcell.00095.2018","article-title":"Blood-brain barrier dysfunction in ischemic stroke: Targeting tight junctions and transporters for vascular protection","volume":"315","author":"Abdullahi","year":"2018","journal-title":"Am. J. Phys. Cell Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"a020412","DOI":"10.1101\/cshperspect.a020412","article-title":"The blood-brain barrier","volume":"7","author":"Daneman","year":"2015","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2450712","DOI":"10.1155\/2018\/2450712","article-title":"Effects of angelica gigas nakai as an anti-inflammatory agent in in vitro and in vivo atopic dermatitis models","volume":"2018","author":"Ok","year":"2018","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.jep.2012.07.019","article-title":"The memory ameliorating effects of inm-176, an ethanolic extract of angelica gigas, against scopolamine- or abeta(1-42)-induced cognitive dysfunction in mice","volume":"143","author":"Park","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1248\/bpb.23.884","article-title":"Polyacetylenes from angelica gigas and their inhibitory activity on nitric oxide synthesis in activated macrophages","volume":"23","author":"Choi","year":"2000","journal-title":"Biol. Pharm. Bull."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sowndhararajan, K., and Kim, S. (2017). Neuroprotective and cognitive enhancement potentials of angelica gigas nakai root: A review. Sci. Pharm., 85.","DOI":"10.3390\/scipharm85020021"},{"key":"ref_19","first-page":"1","article-title":"A review of pharmacological effects of angelica gigas, angelica sinensis, angelica acutiloba and their bioactive compounds","volume":"32","author":"Kim","year":"2011","journal-title":"J. Korean Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lee, T.K., Kim, B., Kim, D.W., Ahn, J.H., Sim, H., Lee, J.C., Yang, G.E., Her, Y., Park, J.H., and Kim, H.S. (2020). Effects of decursin and angelica gigas nakai root extract on hair growth in mouse dorsal skin via regulating inflammatory cytokines. Molecules, 25.","DOI":"10.3390\/molecules25163697"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"29","DOI":"10.4196\/kjpp.2019.23.1.29","article-title":"Decursin induces apoptosis in glioblastoma cells, but not in glial cells via a mitochondria-related caspase pathway","volume":"23","author":"Oh","year":"2019","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Oh, T.W., Park, K.H., Jung, H.W., and Park, Y.K. (2015). Neuroprotective effect of the hairy root extract of angelica gigas nakai on transient focal cerebral ischemia in rats through the regulation of angiogenesis. BMC Complement. Altern. Med., 15.","DOI":"10.1186\/s12906-015-0589-4"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1007\/s11064-015-1623-0","article-title":"The neuroprotective effects of decursin isolated from angelica gigas nakai against amyloid beta-protein-induced apoptosis in pc 12 cells via a mitochondria-related caspase pathway","volume":"40","author":"Li","year":"2015","journal-title":"Neurochem. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s12974-017-0897-3","article-title":"Sac-1004, a vascular leakage blocker, reduces cerebral ischemia-reperfusion injury by suppressing blood-brain barrier disruption and inflammation","volume":"14","author":"Zhang","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sapkota, A., Gaire, B.P., Cho, K.S., Jeon, S.J., Kwon, O.W., Jang, D.S., Kim, S.Y., Ryu, J.H., and Choi, J.W. (2017). Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0171479"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1007\/s12272-016-0835-4","article-title":"Guhong injection protects against focal cerebral ischemia-reperfusion injury via anti-inflammatory effects in rats","volume":"40","author":"Ai","year":"2017","journal-title":"Arch. Pharmacal Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.3892\/etm.2015.2794","article-title":"Novel antiepileptic drug lacosamide exerts neuroprotective effects by decreasing glial activation in the hippocampus of a gerbil model of ischemic stroke","volume":"10","author":"Ahn","year":"2015","journal-title":"Exp. Ther. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.expneurol.2011.03.015","article-title":"Pre- and post-treatments with escitalopram protect against experimental ischemic neuronal damage via regulation of bdnf expression and oxidative stress","volume":"229","author":"Lee","year":"2011","journal-title":"Exp. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00213-004-1795-9","article-title":"Hippocampal function in cognition","volume":"174","author":"Sweatt","year":"2004","journal-title":"Psychopharmacology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/nrn2335","article-title":"The hippocampus and memory: Insights from spatial processing","volume":"9","author":"Bird","year":"2008","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_31","unstructured":"Preedy, V.R. (2016). Neuropathology of Drug Addictions and Substance Misuse Volume 1: Foundations of Understanding, Tobacco, Alcohol, Cannabinoids and Opioids, Academic Press."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.phrs.2006.06.009","article-title":"Neuroprotective effects of fetmpyp: A peroxynitrite decomposition catalyst in global cerebral ischemia model in gerbils","volume":"54","author":"Dhar","year":"2006","journal-title":"Pharmacol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"505","DOI":"10.4142\/jvs.2018.19.4.505","article-title":"Transient forebrain ischemia induces impairment in cognitive performance prior to extensive neuronal cell death in mongolian gerbil (meriones unguiculatus)","volume":"19","author":"Kondo","year":"2018","journal-title":"J. Vet. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kim, B., Lee, T.K., Park, C.W., Kim, D.W., Ahn, J.H., Sim, H., Lee, J.C., Yang, G.E., Kim, J.D., and Shin, M.C. (2020). Pycnogenol((r)) supplementation attenuates memory deficits and protects hippocampal ca1 pyramidal neurons via antioxidative role in a gerbil model of transient forebrain ischemia. Nutrients, 12.","DOI":"10.3390\/nu12082477"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s42826-020-00057-x","article-title":"Brain factor-7(r) improves learning and memory deficits and attenuates ischemic brain damage by reduction of ros generation in stroke in vivo and in vitro","volume":"36","author":"Noh","year":"2020","journal-title":"Lab. Anim. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4067","DOI":"10.1111\/febs.13412","article-title":"The dynamic blood-brain barrier","volume":"282","author":"Keaney","year":"2015","journal-title":"FEBS J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1046\/j.1469-7580.2002.00064.x","article-title":"Astrocyte-endothelial interactions and blood-brain barrier permeability","volume":"200","author":"Abbott","year":"2002","journal-title":"J. Anat."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1002\/term.2692","article-title":"Early iv-injected human dermis-derived mesenchymal stem cells after transient global cerebral ischemia do not pass through damaged blood-brain barrier","volume":"12","author":"Ahn","year":"2018","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"661","DOI":"10.3892\/mmr.2017.6671","article-title":"Transient cerebral ischemia induces albumin expression in microglia only in the ca1 region of the gerbil hippocampus","volume":"16","author":"Park","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.1007\/s11064-020-03094-z","article-title":"Long-term alternating fasting increases interleukin-13 in the gerbil hippocampus, but does not protect bbb and pyramidal neurons from ischemia-reperfusion injury","volume":"45","author":"Lee","year":"2020","journal-title":"Neurochem. Res."},{"key":"ref_41","unstructured":"Council, N.R. (2010). Guide for the Care and Use of Laboratory Animals, National Academies Press."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.jpba.2007.09.020","article-title":"The simultaneous determination of coumarins in angelica gigas root by high performance liquid chromatography-diode array detector coupled with electrospray ionization\/mass spectrometry","volume":"46","author":"Ahn","year":"2008","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_43","unstructured":"Carpenter, J., and Marion, C. (2013). Exotic Animal Formulary, Elsevier."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1759091417726607","DOI":"10.1177\/1759091417726607","article-title":"Mitogen- and stress-activated protein kinase 1 regulates status epilepticus-evoked cell death in the hippocampus","volume":"9","author":"Choi","year":"2017","journal-title":"ASN Neuro"},{"key":"ref_45","first-page":"327","article-title":"Phenotypic alterations in hippocampal npy- and pv-expressing interneurons in a presymptomatic transgenic mouse model of alzheimer\u2019s disease","volume":"8","author":"Mahar","year":"2016","journal-title":"Front. Aging Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00429-016-1259-0","article-title":"Brain atlas of the mongolian gerbil (meriones unguiculatus) in ct\/mri-aided stereotaxic coordinates","volume":"221","author":"Schuller","year":"2016","journal-title":"Brain Struct. Funct."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jneumeth.2015.07.022","article-title":"Comparison of unbiased estimation of neuronal number in the rat hippocampus with different staining methods","volume":"254","author":"Zhu","year":"2015","journal-title":"J. Neurosci. Methods"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0006-8993(00)02513-0","article-title":"Fluoro-jade b: A high affinity fluorescent marker for the localization of neuronal degeneration","volume":"874","author":"Schmued","year":"2000","journal-title":"Brain Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.expneurol.2004.11.025","article-title":"Regional distribution of fluoro-jade b staining in the hippocampus following traumatic brain injury","volume":"193","author":"Anderson","year":"2005","journal-title":"Exp. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1590\/S0004-282X2008000300020","article-title":"Immunohistochemical expression of markers ki-67, neun, synaptophysin, p53 and her2 in medulloblastoma and its correlation with clinicopathological parameters","volume":"66","author":"Meurer","year":"2008","journal-title":"Arq. Neuro Psiquiatr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1365-2818.2009.03146.x","article-title":"Quantitative assessment of relative changes of immunohistochemical staining by light microscopy in specified anatomical regions","volume":"234","author":"Paizs","year":"2009","journal-title":"J. Microsc."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/8\/2161\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:27:27Z","timestamp":1760365647000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/8\/2161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,9]]},"references-count":51,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["molecules26082161"],"URL":"https:\/\/doi.org\/10.3390\/molecules26082161","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,9]]}}}