Hypoxic-ischemic (HI)
brain injury is one of the most common neurological problems occurring in premature and full-term infants after perinatal complications.
Hypothermia is the only treatment approved for HI
encephalopathy in newborns. However, this treatment is only partially protective, cannot be used to treat premature infants, and has limited efficacy to treat severe HI
encephalopathy.
Inflammation contributes to the evolution of HI
brain injury in neonates.
Inter-alpha Inhibitor Proteins (IAIPs) are immunomodulatory
proteins that have neuroprotective properties after exposure to moderate HI in neonatal rats. The objective of the current study was to determine the neuroprotective efficacy of treatment with IAIPs starting immediately after or with a delay of one hour after exposure to severe HI of 120 min duration. One hundred and forty-six 7-day-old rat pups were randomized to
sham control, HI and immediate treatment with IAIPs (60 mg/kg) or placebo (PL), and
sham, HI and
delayed treatment with IAIPs or PL. IAIPs or PL were given at zero, 24, and 48 h after HI or 1, 24 and 48 h after HI. Total
brain infarct volume was determined 72 h after exposure to HI. Treatment with IAIPs immediately after HI decreased (P < 0.05)
infarct volumes by 58.0% and 44.5% in male and female neonatal rats, respectively.
Delayed treatment with IAIPs after HI decreased (P < 0.05)
infarct volumes by 23.7% in male, but not in female rats. We conclude that IAIPs exert
neuroprotective effects even after exposure to severe HI in neonatal rats and appear to exhibit some sex-related differential effects.