Neonatal Models Of Hypoxiaischemia

Until now, the most commonly used model to study hypoxic-ischemic injury in the newborn has been the Rice-Vannucci model in 7-day-old (P7, 12-20 g) rats (Rice et al., 1981), adapted on the Levine procedure (Levine, 1960). The left or right common carotid artery (CCA) was cut between double ligatures of prolene sutures (see Figure 42.1A).

After the surgical procedure the wounds were infiltrated with a local anesthetic, and the pups were allowed to recover for one to two hours. The litters were placed in a chamber perfused with a humidified gas mixture (8% oxygen in nitrogen) for 1.5 hour. The temperature in the incubator, and the temperature of the water used to humidify the gas mixture, were kept at 36°C. After hypoxic exposure the pups were returned to their biological dam to recover for several hours or days (see Figure 42.1). The damage usually is restricted to the hemisphere ipsilateral to the ligation and is observed primarily in the cerebral cortex, subcortical and periventricular white matter, striatum/thalamus, and hippocampus. Such neuropathological damage is rarely seen in the contralateral hemisphere and never in pups rendered hypoxic without ligation (Towfighi et al., 1995; Vannucci and Vannucci, 1997). However, it suffers from a certain degree of variability (animals with an infarct score ranging from 0, no infarct, to 3, very large infarct). Therefore, authors have modified two variables (FiO2 and hypoxia duration) to decrease this variability and obtain a more or less reproducible lesion in most of all animals (see Table 42.1). For example, such a model performed in Hagberg's laboratory with a standardized 7.7% O2 for 55 min gives a total infarct volume of 42.3 ± 15.4 mm3 (Zhu et al., 2003). Many investigators have used this technique to study neonatal asphyxia in several newborn species (rat pups, piglets, dogs, kittens) (Roohey et al., 1997). This model was also recently extended to the immature mouse (Sheldon et al., 1998), with 10% oxygen (see Table 42.1). However, it was found that some strains (CD1) are

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