Article Text

  1. D. F. Meyn1,
  2. C. R. Harvey1,
  3. J. N. Ness1
  1. 1University of Alabama at Birmingham, Birmingham, AL.


Background Neonatal hypoxic-ischemic (HI) injury is mediated by both caspase-dependent and caspase-independent pathways. Prior studies in our laboratory have demonstrated that p53 increases 6 to 12 hours after neonatal HI and that deficiency of p53 decreases neonatal HI by 50%, suggesting that p53 is involved in neuronal death following neonatal HI. Apoptosis-inducing factor (AIF) is an important mediator of caspase-independent apoptosis, and recent evidence from other investigators has shown that AIF may be regulated by p53. However, the mechanistic relationship between p53 and AIF in neonatal HI remains unclear.

Purpose To determine whether AIF immunoreactivity is influenced by neonatal HI and if deficiency of p53 affects this process.

Methods Postnatal day 7 mice underwent left carotid ligation followed by a 1-hour exposure to 8% oxygen and then were sacrificed 3, 6, 9, 12, and 24 hours later. These samples were processed for immunohistochemistry and for Western blotting using antibodies against p53 and AIF.

Results Robust increases in p53 and AIF immunoreactivity were seen 6 to 12 hours after neonatal HI in the CA-1 hippocampal region. This was noted in the same distribution as that observed for nuclear pyknosis. Mice deficient in p53 demonstrated both smaller infarct size and decreased AIF immunoreactivity.

Conclusions These studies demonstrate that p53 and AIF are increased after neonatal HI and that this increase in AIF may be p53 dependent.

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