A New Method for Inducing Perinatal Asphyxia in Rats Incorporating Within-Litter, Non-Ischemic Controls

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Perinatal asphyxia results in impairment in blood-gas exchange and occurs in approximately 1-6 per 1,000 live full-time births, leading to increased rates of infant mortality and long-term neurological deficits. Animal models of perinatal asphyxia leading to hypoxic ischemia continue to be developed. However, relatively few studies actually describe true intrauterine hypoxic ischemia. Here we report on a new method for controlled perinatal asphyxia in the rat that induces a moderate (12 minute) period of hypoxic ischemia and provides within-litter, non-asphyxiated controls. On the day of parturition (gestational day 22), pregnant Sprague-Dawley dams were situated with lower bodies immersed in buffered isotonic saline bath (37.5° C) and the uterus externalized. Surgical silk was used to ligate one uterine artery for 12 min, a duration shown to produce significant effects on brain and behavior. Because of the rat’s duplex uterus with independent arterial flow to each horn, ligation of blood flow and, thus, perinatal asphyxiation of fetuses in one horn was achieved without deleterious effects on the second horn. Blood-gas was analyzed immediately following caesarian delivery. Our results show a significant reduction in blood pH and disruption of CO2/O2 blood-gas levels for perinatal asphyxiated animals, as compared to intrauterine controls. Functional assessments, such as neonatal movement and rate of respiration, were also analyzed. Neuronal damaged was assessed via measurement of whole brain lactate and identification of necrotic foci. Collectively our results demonstrate the expected effects of an intrauterine event that leads to hypoxic ischemia, validating a new model of perinatal asphyxia that provides within-litter, intrauterine controls.


Abstract of poster presented at the 38th Annual Meeting of the Society for Neuroscience, Washington, DC, November 15-19, 2008.