Recent studies have demonstrated that
apolipoprotein E (
APOE) deficiency worsened neuronal
injuries after transient focal and global
cerebral ischemia. However, the molecular mechanism underlying the protective effect of
APOE remains uncertain, even though several mechanisms, including excitotoxicty,
free radicals, and apoptosis, have been cited as causes of selective neuronal vulnerability in
cerebral ischemia. In the present study, we first compared the vulnerability of cultured neurons prepared from APOE-knockout mice upon exposure to
glutamate,
hydrogen peroxide, and
staurosporine. No significant difference in cell viability was observed after exposure to
glutamate or
staurosporine between
APOE-deficient and wild-type mice. However, exposure to
hydrogen peroxide significantly increased the level of cell death in
APOE-deficient mice compared with that in wild-type mice. After transient forebrain
ischemia for 12 min,
APOE-deficient mice showed more neuronal death than wild-type mice. Pretreatment of
APOE-deficient mice with
vitamin E for 2 months markedly reduced neuronal death caused by
ischemia. The results suggest that
APOE exerted its
neuroprotective effect against
ischemia through its
antioxidant action but not through mitigation of
glutamate toxicity or blocking of apoptosis.