Apolipoprotein E deficiency worsens outcome from global cerebral ischemia in the mouse.
OBJECTIVE
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.
Sheng
H
H
Departments of Anesthesiology, Duke University Medical Center, Durham, NC, USA.
Laskowitz
D T
DT
Mackensen
G B
GB
Kudo
M
M
Pearlstein
R D
RD
Warner
D S
DS
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D001157:Arterial Occlusive Diseases / Q000378:metabolism*; D001784:Blood Gas Analysis; D001794:Blood Pressure; D002545:Brain Ischemia / Q000378:metabolism*; D002531:Cerebellum / Q000098:blood supply; D002540:Cerebral Cortex / Q000098:blood supply; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000098:blood supply; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017072:Neostriatum / Q000098:blood supply; D011149:Pons / Q000098:blood supply; D013788:Thalamus / Q000098:blood supply
D001057:Apolipoproteins E