W E Van Nostrand1, J Davis, M L Previti, F Xu. 1. Department of Neurosurgery and Medicine, Stony Brook University, Stony Brook, NY 11794-8122, USA. William.VanNostrand@sbumed.org
Abstract
BACKGROUND/AIMS: There is increased amyloid-β protein precursor (AβPP) expression and amyloid-β protein (Aβ) production in the brain shortly following cerebral ischemic stroke in rodent models. It has been postulated that this may seed amyloid deposition in the brain. On the other hand, it remains unclear how cerebral ischemia affects preexisting Aβ deposits in the brain. Here we determine the consequences of focal ischemic stroke on existing Aβ pathology in Tg-SwDI transgenic mice. METHODS: At 12 months of age, Tg-SwDI mice were subjected to photo-induced focal cerebral ischemia in one hemisphere. One, 7, or 21 days after lesioning, the amount of deposited Aβ in the ischemic and control hemispheres was measured using ELISA. Image analysis was used to visualize deposited Aβ and the presence of microglia/macrophages. RESULTS: After 7 days, and further after 21 days, there was a dramatic reduction in the amount of deposited Aβ and increased presence of microglia/macrophages in the ischemic hemisphere of the mice. CONCLUSIONS: Focal cerebral ischemia leads to clearance of deposited Aβ in Tg-SwDI mice starting at 7 days with almost complete removal in the ischemic area by 21 days. The delayed clearance of Aβ following focal cerebral ischemia may involve the infiltration of activated neuroinflammatory cells.
BACKGROUND/AIMS: There is increased amyloid-β protein precursor (AβPP) expression and amyloid-β protein (Aβ) production in the brain shortly following cerebral ischemic stroke in rodent models. It has been postulated that this may seed amyloid deposition in the brain. On the other hand, it remains unclear how cerebral ischemia affects preexisting Aβ deposits in the brain. Here we determine the consequences of focal ischemic stroke on existing Aβ pathology in Tg-SwDI transgenic mice. METHODS: At 12 months of age, Tg-SwDI mice were subjected to photo-induced focal cerebral ischemia in one hemisphere. One, 7, or 21 days after lesioning, the amount of deposited Aβ in the ischemic and control hemispheres was measured using ELISA. Image analysis was used to visualize deposited Aβ and the presence of microglia/macrophages. RESULTS: After 7 days, and further after 21 days, there was a dramatic reduction in the amount of deposited Aβ and increased presence of microglia/macrophages in the ischemic hemisphere of the mice. CONCLUSIONS:Focal cerebral ischemia leads to clearance of deposited Aβ in Tg-SwDI mice starting at 7 days with almost complete removal in the ischemic area by 21 days. The delayed clearance of Aβ following focal cerebral ischemia may involve the infiltration of activated neuroinflammatory cells.
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Authors: Judianne Davis; Feng Xu; Rashid Deane; Galina Romanov; Mary Lou Previti; Kelly Zeigler; Berislav V Zlokovic; William E Van Nostrand Journal: J Biol Chem Date: 2004-02-25 Impact factor: 5.157
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