Mitochondria are More Resistant to Hypoxic Depolarization in the Newborn than in the Adult Brain
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Hypoxic–ischemic brain injury subsequent to asphyxia represents a major cause of morbidity and death in the newborn. The newborn brain has been considered more resistant to hypoxia than the adult brain because of lower energy demand. The mechanisms underlying hypoxic brain injury, in particular the age-related vulnerability, are still only partially understood. The mitochondrial function is pivotal for the function and survival of neurons. Acutely isolated CA1 neurons from neonatal (3–6 days) and adult rats (5–6 weeks) were loaded with Rh 123, and the effect of hypoxia on the inner mitochondrial membrane potential (Δψm) was compared. During prolonged hypoxia (15 min), Δψm was lost in a majority of the neonatal neurons (83%) and in all the adult neurons. During hypoxia (5 min) followed by reoxygenation the mitochondria in 23% of the neonatal neurons were completely depolarized, whereas 85% of the adult neurons demonstrated a complete loss of Δψm. In conclusion hippocampal CA1 mitochondria in the newborn rat are more resistant to hypoxic depolarization than in the adult rat.
KeywordsMitochondrial membrane potential Hippocampus CA1 neurons Hypoxia Rhodamine 123 Neonatal brain Age Hypoxic tolerance
This work was supported by grants from the National Council on Cardiovascular Diseases, the Research Council of Norway, The Malthe Foundation, Oslo, Norway and the Blix Family Foundation, Oslo, Norway. We thank Professor Ansgar O. Aasen for providing excellent working conditions.
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