BACKGROUND AND PURPOSE: Apolipoprotein E (apoE) has been found relevant in a variety of central nervous system disorders. This experiment examined the effect of endogenous murine apoE on selective neuronal necrosis resulting from a transient forebrain ischemia insult. METHODS: ApoE deficient (n=16) and wild type (n=17) halothane-anesthetized mice were subjected to severe forebrain ischemia (10 minutes of bilateral carotid occlusion and systemic hypotension). After 3 days' recovery, brain injury was determined histologically. In other apoE-deficient and wild-type mice, regional cerebral blood flow (CBF) was determined by 14C-iodoantipyrine autoradiography 10 minutes before, 5 minutes after onset of, and 30 minutes after reperfusion from 10 minutes of forebrain ischemia. RESULTS: The percentage of dead hippocampal CA1 neurons (mean+/-SD) was greater in the apoE-deficient group (apoE deficient=67+/-30%; wild type=37+/-33%; P=0.011). A similar pattern was observed in the caudoputamen (P=0.002) and neocortex (P=0.014). Cerebral blood flow was similar between groups at each measurement interval. Marked hypoperfusion persisted in both groups at 30 minutes after ischemia. CONCLUSIONS: ApoE deficiency worsens ischemic outcome. This is not attributable to effects on CBF. A role of apoE in the cerebral response to global ischemia is consistent with prior reports that murine apoE deficiency increases infarct size resulting from focal cerebral ischemia.
BACKGROUND AND PURPOSE:Apolipoprotein E (apoE) has been found relevant in a variety of central nervous system disorders. This experiment examined the effect of endogenous murineapoE on selective neuronal necrosis resulting from a transient forebrain ischemia insult. METHODS:ApoE deficient (n=16) and wild type (n=17) halothane-anesthetized mice were subjected to severe forebrain ischemia (10 minutes of bilateral carotid occlusion and systemic hypotension). After 3 days' recovery, brain injury was determined histologically. In other apoE-deficient and wild-type mice, regional cerebral blood flow (CBF) was determined by 14C-iodoantipyrine autoradiography 10 minutes before, 5 minutes after onset of, and 30 minutes after reperfusion from 10 minutes of forebrain ischemia. RESULTS: The percentage of dead hippocampal CA1 neurons (mean+/-SD) was greater in the apoE-deficient group (apoE deficient=67+/-30%; wild type=37+/-33%; P=0.011). A similar pattern was observed in the caudoputamen (P=0.002) and neocortex (P=0.014). Cerebral blood flow was similar between groups at each measurement interval. Marked hypoperfusion persisted in both groups at 30 minutes after ischemia. CONCLUSIONS: ApoE deficiency worsens ischemic outcome. This is not attributable to effects on CBF. A role of apoE in the cerebral response to global ischemia is consistent with prior reports that murineapoEdeficiency increases infarct size resulting from focal cerebral ischemia.
Authors: Jeffrey T Guptill; Shruti M Raja; Felix Boakye-Agyeman; Robert Noveck; Sarah Ramey; Tian Ming Tu; Daniel T Laskowitz Journal: J Clin Pharmacol Date: 2016-12-19 Impact factor: 3.126
Authors: Diewertje I Bink; Katja Ritz; Eleonora Aronica; Louise van der Weerd; Mat J A P Daemen Journal: J Cereb Blood Flow Metab Date: 2013-08-21 Impact factor: 6.200