Neurometabolic Alterations in the Acute Postnatal Phase of Perinatal Asphyxia in the Rat

Perinatal hypoxic-ischemic encephalopathies represent a range of intrauterine and birth complications that, in cases most severe, can result in mental retardation, cerebral palsy, or death. More recent clinical studies have indicated that perinatal hypoxic-ischemia may play a causal role in etiology of cognitive deficits in the absence of motor disorders. To further evaluate this role, we have utilized an intrauterine model of a one-time perinatal asphyxic event in the rat that provides normoxic, within-litter controls and preserves many clinically-relevant features of this dynamic, late-gestational time period. Our current findings show significant disturbances immediately following birth in pH, pCO2, and pO2, as measured in mixed arterial and venous blood samples from asphyxiated, non-asphyxiated, and vaginal-born rat pups an indication of metabolic acidosis. We have additionally found a significant increase in the concentration of brain lactate levels (a marker hypoxic-ischemic encephalopathy) immediately following birth in asphyxiated (56.5 ± 2.9 μg/dl) as compared to non-asphyxiated (24.4 ± 1.1 μg/dl) and vaginal-born rats (29.6 ± 3.2 μg/dl). At one hour postnatal, average whole brain lactate concentrations were measurably lower, but remained significantly elevated in the asphyxiated group (23.9 ± 3.6 μg/dl) versus non-asphyxiated (11.7 ± 3.1 μg/dl) and vaginal-born (7.5 ± 0.74 μg/dl). Linear regression analysis revealed low blood pH to be an accurate indicator of elevated brain lactate concentration at one hour postnatal (R2 = 0.495; p=0.003). One important consideration in the interpretation of these findings is the role of lactate metabolism in the neonatal mammal as a secondary energy source. This consideration necessitates a more detailed investigation of neural high-energy phosphate levels during the acute postnatal phase of increased whole-brain lactate concentration. Current work with this model is aimed at just such an investigation utilizing 31P NMR spectroscopy, a technique with increasing clinical relevance in the assessment of neonatal hypoxic-ischemic encephalopathy.