Effects of memantine and melatonin on signal transduction pathways vascular leakage and brain injury after focal cerebral ischemia in mice

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dc.authorid0000-0001-6494-8923
dc.contributor.authorKılıç, Ülkan
dc.contributor.authorYılmaz, Bayram
dc.contributor.authorReiter, Rüssel
dc.contributor.authorYüksel, Adnan
dc.contributor.authorKılıç, Ertuğrul
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T20:02:01Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T20:02:01Z
dc.date.issued2013
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı
dc.descriptionWOS: 000317537800026
dc.descriptionPubMed ID: 23396088
dc.description.abstractBecause of their favorable action profiles in humans, both memantine and melatonin are particularly interesting candidates as neuroprotectants in acute ischemic stroke. Until now, the signaling mechanisms mediating memantine's neuroprotective actions remained essentially uninvestigated. In addition, we have combined memantine with melatonin, which is a well-known neuroprotective molecule. Herein, we examined the effects of memantine (20 mg/kg, i.p.) administered alone or in combination with melatonin (4 mg/kg, i.p.) on the activation of signaling transduction pathways, IgG extravasation and ischemic injury in mice submitted to 90 min of intraluminal middle cerebral artery occlusion, followed by 24 h of reperfusion. In these studies, both agents reduced ischemic injury and the density of DNA-fragmentation. Notably, melatonin/memantine combination reduced ischemic injury further as compared with memantine treatment, which was associated with reduced IgG extravasation, indicating vascular leakage in the brain. Animals receiving memantine exhibited elevated ERK-1/2 and decreased p21 and p38/MAPK activations, while it had no significant effect on phosphorylated Akt and SAPK/JNK1/2 in the ischemic brain. However, melatonin increased the activation of Akt and reduced the activations of ERK-1/2, p21, p38/MAPK and SAPK/JNK1/2 significantly. Synergistic effects of memantine and melatonin were observed in the inactivation of p21, p38/MAPK and SAPK/JNK1/2 pathways. Moreover, memantine reversed the effects of melatonin on the activation of ERK-1/2 pathway. Here, we provide evidence that free radical scavenger melatonin potentiates the effects of memantine on ischemic brain injury via inactivations of p21 and stress kinases p38/MAPK and SAPK/JNK1/2 pathways.
dc.description.sponsorshipEMBO (European Molecular Biology Organization); Turkish Academy of Sciences (TUBA/GEBIP)en_US
dc.description.sponsorshipWe thank M. Ugur and S. Eyuboglu for technical assistance. This work was supported by EMBO (European Molecular Biology Organization) installation Grant and The Turkish Academy of Sciences (TUBA/GEBIP).en_US
dc.identifier.citationKılıç, Ü., Yılmaz, B., Reiter, R., Yüksel, A. ve Kılıç, E. (2013). Effects of memantine and melatonin on signal transduction pathways vascular leakage and brain injury after focal cerebral ischemia in mice. Neuroscience, 237, 268-276. https://dx.doi.org/10.1016/j.neuroscience.2013.01.059
dc.identifier.doi10.1016/j.neuroscience.2013.01.059
dc.identifier.endpage276
dc.identifier.issn0306-4522
dc.identifier.scopusqualityQ2
dc.identifier.startpage268
dc.identifier.urihttps://dx.doi.org/10.1016/j.neuroscience.2013.01.059
dc.identifier.urihttps://hdl.handle.net/20.500.12511/3526
dc.identifier.volume237
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherPergamon-Elsevier Science Ltd
dc.relation.ispartofNeuroscienceen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectMelatonin
dc.subjectMemantine
dc.subjectCerebral Ischemia
dc.subjectCell Signaling
dc.subjectBlood-Brain Barrier Permeability
dc.titleEffects of memantine and melatonin on signal transduction pathways vascular leakage and brain injury after focal cerebral ischemia in mice
dc.typeArticle

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