title: Susceptibility to focal and global brain ischemia of Alzheimer mice displaying aβ deposits: effect of immunoglobulin.
abstract: Cerebral ischemia is a risk factor for Alzheimer's disease (AD). Moreover, recent evidence indicates that it is a two-way street as the incidence rate of stroke is significantly higher in AD patients than those without the disease. Here we investigated the interaction of ischemic brain insults and AD in 9-month-old ApdE9 mice, which show full-blown accumulation of Aβ deposits and microgliosis in the brain. Permanent occlusion of the middle cerebral artery (pMCAo) resulted in 36% larger infarct in ApdE9 mice compared to their wild-type (wt) controls. This was not due to differences in endothelium-dependent vascular reactivity. Treatment with human intravenous immunoglobulin (IVIG) reduced the infarct volumes and abolished the increased vulnerability of ApdE9 mice to pMCAo induced brain ischemia. When the mice were exposed to global brain ischemia (GI), an insult of hippocampal cells, ApdE9 mice showed increased neuronal loss in CA2 and CA3 subregions compared to their wt controls. GI was associated with increased microgliosis, astrogliosis, infiltration of blood-derived monocytic cells, and neurogenesis without clear differences between the genotypes. IVIG treatment prevented the GI-induced neuron loss in hippocampal CA1 and CA3 regions in ApdE9 mice. IVIG treatment increased microgliosis in wt but not in ApdE9 mice. Finally, GI induced 60% reduction in the hippocampal Aβ burden in ApdE9 mice, which was not affected by IVIG treatment. The results indicate that the AD pathology with Aβ deposits and microgliosis increases ischemic vulnerability in various brain areas. Moreover, IVIG treatment may be beneficial especially in patients suffering from both acute ischemic insult and AD.
authors.affiliation: A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI-70211 Kuopio, Finland.
authors.forename: Riikka
authors.initials: R
authors.lastname: Heikkinen
authors.affiliation: A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI-70211 Kuopio, Finland.
authors.forename: Tarja
authors.initials: T
authors.lastname: Malm
authors.affiliation: Kuopio University Hospital, PL100, 70029 KYS, Kuopio, Finland.
authors.forename: Janne
authors.initials: J
authors.lastname: Heikkilä
authors.affiliation: Medeia Therapeutics Ltd, FI-70211 Kuopio, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Muona
authors.affiliation: A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI-70211 Kuopio, Finland ; Department of Neurology, Kuopio University Hospital, FI-70211 Kuopio, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Tanila
authors.affiliation: Medeia Therapeutics Ltd, FI-70211 Kuopio, Finland.
authors.forename: Milla
authors.initials: M
authors.lastname: Koistinaho
authors.affiliation: A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI-70211 Kuopio, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Koistinaho
keywords: Alzheimer’s disease; ApdE9 mice; IVIG treatment; global ischemia; hippocampus
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