<p>Effects of early administration of insulin-like growth factor-1 on cognitive function in septic encephalopathy</p>

Abstract

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.

Research Progress of Macromolecules in the Prevention and Treatment of Sepsis

“…FGF-15 is an analog of FGF-19, which significantly improves liver inflammation and apoptosis in septic mice by targeting fibroblast growth factor receptor 4, reducing the proportion of Tregs, and increasing the survival rate of septic mice by 40% [ 36 ]. Insulin-like growth factor 1, which is an anti-apoptosis factor, reduces hippocampal apoptosis and improves cognitive impairment by inhibiting the overexpression of cytochrome c and tumor necrosis factor receptors in a rat model of septic encephalopathy (SE) [ 38 ]. Maf1 is a transcriptional regulator of RNA polymerase III that reduces inflammation and apoptosis by competitively binding to the NLRP3 and inhibiting the expression and activity of NLRP3.…”

The role of IGF-1 in exercise to improve obesity-related cognitive dysfunction

“…Increased level of IGF-1 may protect cognitive function. Subcutaneous injection of IGF-1 into rats during the early stage of sepsis (within 6 h) could reduce cell apoptosis, improve the performance of septic rats in MWM and passive avoidance experiments, and protect their memory and spatial learning abilities ( Yang et al, 2019 ). Similarly, IGF-1 gene treatment in rats with traumatic brain injury reduced oxidative stress generated in the prefrontal cortex, motor cortex and hippocampus and improved the performance of rats in the Y-maze, promoting their working memory capacity and preventing cognitive deficits caused by traumatic brain injury ( Montivero et al, 2021 ).…”

Insulin-Like Growth Factor-1 (IGF-1) and Its Monitoring in Medical Diagnostic and in Sports

“…IGF-1 levels have been shown to be decreased in children with Meningococcal sepsis and more so in those for whom the infection was fatal [ 83 ]. The potential for IGF-1 replacement as a treatment for both the prevention and management of sepsis has been demonstrated in mice where it improved overall survival rates through enhanced hepatic bacterial clearance [ 84 ] and in rats as a cognitive therapeutic when administered within 6 h of septic encephalopathy [ 85 ].…”