Effects of early administration of insulin-like growth factor-1 on cognitive function in septic encephalopathy.

backgroundBoth protective and therapeutic functions of insulin-like growth factor-1 (IGF-1) in brain injury have been reported, but its effects on cognitive sequelae after septic encephalopathy (SE) remain unclear. MATERIALS AND

methodsThis study was divided into three parts, and a septic model was built by cecal ligation and puncture (CLP). First, survival analysis was performed, and IGF-1's effects on long-term cognition and depressive emotion were assessed. Second, the characteristics of IGF-1 function in cognition were evaluated. Finally, cytochrome C, caspase-9, tumor necrosis factor receptor (TNFR), and caspase-8 levels as well as cell apoptosis in the hippocampus were evaluated.

resultsIGF-1 did not reduce mortality or alleviate depressive symptoms in septic rats, but improved the memory of noxious stimulation and spatial learning and memory. These effects were observed only when IGF-1 was administered within 0-6 hours after CLP. Moreover, cytochrome C and caspase-9 expression levels were increased at 6 hours after CLP in the hippocampus, while TNFR and caspase-8 amounts were not increased until 12 hours after CLP. Cell apoptosis increased at 12 hours after CLP, but was inhibited by IGF-1.

conclusionCognitive impairment in rats recovering from SE is associated with cell apoptosis in the hippocampus. Supplementation of IGF-1 reduces cell apoptosis by preventing the over-expression of cytochrome C and TNFR, and results in improved cognitive function. However, improvement only occurs when IGF-1 is administered at the early stage (within 6 hours) of sepsis. As cytochrome C activation occurs earlier than that of TNFR in this study, cytochrome C may be the main factor inducing apoptosis in early SE.