title: Poloxamer-188 and citicoline provide neuronal membrane integrity and protect membrane stability in cortical spreading depression.
abstract: Under pathological conditions such as brain trauma, subarachnoid hemorrhage and stroke, cortical spreading depression (CSD) or peri-infarct depolarizations contribute to brain damage in animal models of neurological disorders as well as in human neurological diseases. CSD causes transient megachannel opening on the neuronal membrane, which may compromise neuronal survival under pathological conditions. Poloxamer-188 (P-188) and citicoline are neuroprotectants with membrane sealing properties. The aim of this study is to investigate the effect of P-188 and citicoline on the neuronal megachannel opening induced by CSD in the mouse brain. We have monitored megachannel opening with propidium iodide, a membrane impermeable fluorescent dye and, demonstrate that P-188 and citicoline strikingly decreased CSD-induced neuronal PI influx in cortex and hippocampal dentate gyrus. Therefore, these agents may be providing neuroprotection by blocking megachannel opening, which may be related to their membrane sealing action and warrant further investigation for treatment of traumatic brain injury and ischemic stroke.
authors.affiliation: a Department of Neurosurgery, Ankara Atatürk Education and Research Hospital , Ankara , Turkey.
authors.forename: Timur
authors.initials: T
authors.lastname: Yıldırım
authors.affiliation: b Department of Neurosurgery, Konya Numune Hospital , Konya , Turkey.
authors.forename: Alpaslan
authors.initials: A
authors.lastname: Eylen
authors.affiliation: c Institute of Neurological Sciences and Psychiatry, Hacettepe University , Ankara , Turkey.
authors.forename: Sevda
authors.initials: S
authors.lastname: Lule
authors.affiliation: c Institute of Neurological Sciences and Psychiatry, Hacettepe University , Ankara , Turkey.|d Department of Neurology, Faculty of Medicine, Hacettepe University , Ankara , Turkey.
authors.forename: Sefik Evren
authors.initials: SE
authors.lastname: Erdener
authors.affiliation: c Institute of Neurological Sciences and Psychiatry, Hacettepe University , Ankara , Turkey.|d Department of Neurology, Faculty of Medicine, Hacettepe University , Ankara , Turkey.
authors.forename: Atay
authors.initials: A
authors.lastname: Vural
authors.affiliation: c Institute of Neurological Sciences and Psychiatry, Hacettepe University , Ankara , Turkey.|d Department of Neurology, Faculty of Medicine, Hacettepe University , Ankara , Turkey.
authors.forename: Hulya
authors.initials: H
authors.lastname: Karatas
authors.affiliation: e Department of Neurosurgery, Faculty of Medicine, Ordu University , Ordu , Turkey.
authors.forename: Mehmet Faik
authors.initials: MF
authors.lastname: Ozveren
authors.affiliation: c Institute of Neurological Sciences and Psychiatry, Hacettepe University , Ankara , Turkey.|d Department of Neurology, Faculty of Medicine, Hacettepe University , Ankara , Turkey.
authors.forename: Turgay
authors.initials: T
authors.lastname: Dalkara
authors.affiliation: c Institute of Neurological Sciences and Psychiatry, Hacettepe University , Ankara , Turkey.|d Department of Neurology, Faculty of Medicine, Hacettepe University , Ankara , Turkey.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Gursoy-Ozdemir
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D013181:Cortical Spreading Depression / Q000187:drug effects*; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology*; D051379:Mice; D018697:Nootropic Agents / Q000494:pharmacology*; D020442:Poloxamer / Q000494:pharmacology*
chemical_list: D018697:Nootropic Agents; D020442:Poloxamer; D003566:Cytidine Diphosphate Choline
keywords: citicoline; cortical spreading depression; megachannels; neuroprotection; poloxamer-188