High-dose intravenous immunoglobulin exerts neuroprotective effect in the rat model of neonatal asphyxia

Abstract

Background:Neonatal asphyxia is one of the leading causes of death in newborn and permanent neurological disabilities in surviving children. The underlying hypoxic-ischemic (HI) injury triggers an inflammatory response lading to neuronal damage. Here, we tested the hypothesis that high-dose intravenous immunoglobulin (IVIG) could exert immunomodulatory effect in rat pups subjected to HI injury.Methods:HI injury was induced in 7-d-old pups by ligating the common carotid artery followed by exposure to 8% oxygen for 2 h. Brain infarction was evaluated by imaging stained coronal brain sections. Neurological deficits were assessed in weeks 1 through 4 after HI. Western blotting and immunohistochemistry were used to assess complement fragment deposition in the brain tissue.Results:Treatment with IVIG at 2 g/kg significantly and in a dose-responsive manner reduced brain infarction size as well as mortality and neurological deficits caused by HI. Anatomical and functional improvements in IVIG-treated pups correlated with decreased deposition of C3b complement fragments in the injured brain hemisphere.Conclusion:IVIG significantly improved the outcome of HI injury in rat pups and could potentially be used for the treatment of human neonatal asphyxia to target proinflammatory complement fragments. Copyright © 2014 International Pediatric Research Foundation, Inc.