Diabetes mellitus is known to exacerbate acute cerebral ischemic injury. 
Previous studies have demonstrated that infarction volumes caused by transient 
cerebral ischemia were greater in diabetic rats than in nondiabetic rats. Tumor 
necrosis factor-α (TNF-α) is a proinflammatory protein produced in the brain in 
response to cerebral ischemia that promotes apoptosis. Etanercept (ETN), a 
recombinant TNF receptor (p75)-Fc fusion protein, competitively inhibits TNF-α. 
Therefore, we evaluated the neuroprotective effects of chronic or acute 
treatment with ETN on cerebral injury caused by middle cerebral artery 
occlusion/reperfusion (MCAO/Re) in rats with streptozotocin-induced diabetes. 
Furthermore, we evaluated the effects of ETN against the apoptosis and 
myeloperoxidase activity. Single administration of ETN before MCAO significantly 
suppressed exacerbation of cerebral damage in nondiabetic rats, as assessed by 
infarct volume. In contrast, the diabetic state markedly aggravated 
MCAO/Re-induced cerebral damage despite ETN treatment within 24 h before MCAO. 
However, the damage was improved by repeated administration of ETN at 
900 μg/kg/daily in rats in an induced diabetic state. These results suggested 
that repeated administration of ETN can prevent exacerbation of cerebral 
ischemic injury in the diabetic state and is mainly attributed to 
anti-inflammatory effects.