title: Non-selective calcium channel blocker bepridil decreases secondary pathology in mice after photothrombotic cortical lesion.
abstract: Experimental studies have identified a complex link between neurodegeneration, β-amyloid (Aβ) and calcium homeostasis. Here we asked whether early phase β-amyloid pathology in transgenic hAPPSL mice exaggerates the ischemic lesion and remote secondary pathology in the thalamus, and whether a non-selective calcium channel blocker reduces these pathologies. Transgenic hAPPSL (n = 33) and non-transgenic (n = 30) male mice (4-5 months) were subjected to unilateral cortical photothrombosis and treated with the non-selective calcium channel blocker bepridil (50 mg/kg, p.o., once a day) or vehicle for 28 days, starting administration 2 days after the operation. Animals were then perfused for histological analysis of infarct size, Aβ and calcium accumulation in the thalamus. Cortical photothrombosis resulted in a small infarct, which was associated with atypical Aβ and calcium accumulation in the ipsilateral thalamus. Transgenic mice had significantly smaller infarct volumes than non-transgenic littermates (P<0.05) and ischemia-induced rodent Aβ accumulation in the thalamus was lower in transgenic mice compared to non-transgenic mice (P<0.01). Bepridil decreased calcium load in the thalamus (P<0.01). The present data suggest less pronounced primary and secondary pathology in hAPPSL transgenic mice after ischemic cortical injury. Bepridil particularly decreased calcium pathology in the thalamus following ischemia.
authors.affiliation: Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Lipsanen
authors.forename: Stefanie
authors.initials: S
authors.lastname: Flunkert
authors.forename: Kristina
authors.initials: K
authors.lastname: Kuptsova
authors.forename: Mikko
authors.initials: M
authors.lastname: Hiltunen
authors.forename: Manfred
authors.initials: M
authors.lastname: Windisch
authors.forename: Birgit
authors.initials: B
authors.lastname: Hutter-Paier
authors.forename: Jukka
authors.initials: J
authors.lastname: Jolkkonen
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D015764:Bepridil / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D020767:Intracranial Thrombosis / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D008027:Light / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D013788:Thalamus / Q000187:drug effects* / Q000473:pathology* / Q000528:radiation effects
chemical_list: D016229:Amyloid beta-Peptides; D002121:Calcium Channel Blockers; D015764:Bepridil
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