title: KB-R7943, an inhibitor of the reverse Na(+)/Ca(2+) exchanger, does not modify secondary pathology in the thalamus following focal cerebral stroke in rats.
abstract: Remote areas connected to cortical infarcts, such as the thalamus, are affected by stroke due to delayed retrograde degeneration of afferent connections. This is temporally associated with the accumulation of β-amyloid (Aβ) and calcium. Here we tested a hypothesis that prevention of excessive Ca(2+) influx into the axoplasm via the reverse Na(+)/Ca(2+) exchanger (NCX) would provide axonal protection and eventually lessen the Aβ and calcium load in the thalamus. We found that chronic treatment with a specific inhibitor of the reverse NCX, KB-R7943 (30mg/kg once daily, 27 days) after middle cerebral artery occlusion did not prevent atypical secondary pathology in the thalamus or improve functional outcome. The present data do not support a role for reverse NCX activity in the complex pathology within the thalamus after cerebral ischemia.
authors.affiliation: Institute of Clinical Medicine-Neurology, University of Eastern Finland, FIN-70211 Kuopio, Finland. Electronic address: anu.lipsanen@uef.fi.
authors.forename: Anu
authors.initials: A
authors.lastname: Lipsanen
authors.affiliation: Institute of Clinical Medicine-Neurology, University of Eastern Finland, FIN-70211 Kuopio, Finland.
authors.forename: Saara
authors.initials: S
authors.lastname: Parkkinen
authors.affiliation: Institute of Clinical Medicine-Neurology, University of Eastern Finland, FIN-70211 Kuopio, Finland.
authors.forename: Joonas
authors.initials: J
authors.lastname: Khabbal
authors.affiliation: Institute of Clinical Medicine-Neurology, University of Eastern Finland, FIN-70211 Kuopio, Finland.
authors.forename: Petra
authors.initials: P
authors.lastname: Mäkinen
authors.affiliation: School of Pharmacy, Biocenter Kuopio, University of Eastern Finland, FIN-70211 Kuopio, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Peräniemi
authors.affiliation: Institute of Clinical Medicine-Neurology, University of Eastern Finland, FIN-70211 Kuopio, Finland; Institute of Biomedicine, University of Eastern Finland, FIN-70211, Kuopio, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Hiltunen
authors.affiliation: Institute of Clinical Medicine-Neurology, University of Eastern Finland, FIN-70211 Kuopio, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Jolkkonen
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009048:Motor Skills / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism*; D017208:Rats, Wistar; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D013788:Thalamus / Q000187:drug effects* / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D019831:Sodium-Calcium Exchanger; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D013890:Thiourea; D002118:Calcium
keywords: Amyloid precursor protein; Calcium; KB-R7943; Sodium/calcium exchanger; Transient middle cerebral artery occlusion; β-Amyloid