Structural and Functional Effects of C5aR1 Antagonism in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy

Abstract

Plain Language SummaryIn this study, we tested a new treatment for a disease in babies called hypoxic-ischemic encephalopathy (HIE). HIE is caused by restricted oxygen and blood flow around the time of birth, and most damage is caused when blood flow is restored. One reason for this is excess inflammation, which happens because a large amount of specific proteins and chemicals are released. Some inflammation is protective, but excessive inflammation injures healthy tissue, and in HIE this contributes to lifelong physical and mental disabilities, even death. The only treatment for HIE is cooling therapy, but even with this treatment many infants still do not survive or live with permanent disability. We mimicked the disease in rats and then gave them a drug that prevents excess inflammation by binding and disabling specific proteins. We measured improvement by comparing physical and mental abilities and brain damage in the treated rats to untreated and normal rats. Overall, the drug improved many but not all skills and parts of the brain harmed by the disease. More testing needs to be done to determine the optimal dose and if there is additional benefit when the drug is combined with cooling therapy. In closing, our results show this treatment warrants further development and could help infants grow up with less hardship and lead better, healthier lives.