Adenovirus-mediated over-expression of interleukin-1 receptor antagonist reduces susceptibility to excitotoxic brain injury in perinatal rats

摘要: Abstract In seven-day-old rats, intracerebral injection of N-methyl- d -aspartate transiently stimulates expression Interleukin-1β messenger RNA. To evaluate the role in pathogenesis excitotoxic injury, we sought to determine if Interleukin-1 receptor antagonist, an endogenous competitive inhibitor Interleukin-1β, could attenuate -aspartate-induced injury. induce sustained over-expression antagonist brain, a recombinant adenovirus encoding was administered by intracerebroventricular into three-day-old rats. Increased brain concentrations two six days later were documented assays tissue homogenates and immunocytochemistry. impact on neurotoxicity, animals received injections either or control β-galactosidase, followed four right intrastriatal (10 nmol/0.5 μl), dose that typically elicits injury ipsilateral striatum adjacent hippocampus, saline. Animals killed five later, damage quantitated measurement bilateral cross-sectional areas anterior hippocampus. three independent experiments, -aspartate-lesioned animals, both striatal hippocampal injuries reduced had been infected with encoded comparison littermates (right volume loss ranged from 16 24%, compared 54–65% controls). There no atrophy adenovirus-infected saline-injected animals. These results provide strong support for hypothesis is mediator perinatal