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


CONCLUSIONS
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.
Shock, Trauma and Anesthesiology Research Center, Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland.
Bo
B
Chen
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland.
Jeong Seon
JS
Yoon
Shock, Trauma and Anesthesiology Research Center, Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland.
Bingren
B
Hu
BioVisions, Inc., Potomac, Maryland.
Milan
M
Basta
D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000503:physiopathology / Q000628:therapy*; D001835:Body Weight; D001921:Brain / Q000503:physiopathology; D020520:Brain Infarction / Q000188:drug therapy* / Q000473:pathology; D003167:Complement Activation; D003179:Complement C3b / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D016756:Immunoglobulins, Intravenous; D018696:Neuroprotective Agents; D003179:Complement C3b