Apolipoprotein E deficiency worsens outcome from global cerebral ischemia in the mouse

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 f rom a transient forebrain ischemia insult. Methods-ApoE deficient (n = 16) and wild type (n = 17) halothane-anesthetiz ed mice were subjected to severe forebrain ischemia (10 minutes of bilatera l carotid occlusion and systemic hypotension). After 3 days' recovery, brai n injury was determined histologically. In other apoE-deficient and wild-ty pe mice, regional cerebral blood flow (CBF) was determined by C-14-iodoanti pyrine 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 grea ter 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 gro ups at each measurement interval. Marked hypoperfusion persisted in both gr oups at 30 minutes after ischemia. Conclusions-ApoE deficiency worsens ischemic outcome. This is not attributa ble to effects on CBF. A role of apoE in the cerebral response to global is chemia is consistent with prior reports that murine apoE deficiency increas es infarct size resulting from focal cerebral ischemia.