Strain-related brain injury in neonatal mice subjected to hypoxia-ischemia

Abstract

The development of transgenic mice has led to an increase in the use of mice as models for human disease. We hypothesized that the degree of brain damage sustained by animals in a neonatal mouse model of hypoxia-ischemia depends on the strain used. We compared three strains of mice commonly used to generate transgenic strains (C57Bl/6, 129Sv and CD1), as well as three hybrids of these strains (C57Bl/6x129Sv, CD1xC57Bl/6, and CD1x129Sv). At postnatal day 7 (P7), pups were subjected to a modified Vannucci procedure for hypoxia-ischemia as follows: permanent ligation of right common carotid artery under halothane anesthesia, 2-h recovery period, exposure to 8% oxygen at 37 degreesC for varying durations (30, 60 or 90 min). After 5 days, animals were perfused with 4% paraformaldehyde, brains were removed, postfixed and examined histologically with cresyl violet and Perl's iron stain to assess the degree of damage. Damage was assessed blindly using a score ranging from 0 (none) to 3 (infarct) in eight regions (ant-, mid-, and post- cortex, CA1, CA2, CA3 and dentate gyrus of the hippocampus, and striatum). We found significant differences in susceptibility to brain damage and mortality depending on the strain used. While determining the maximal degree of injury with the least amount of mortality for each strain, it was found that some strains (CD1) are particularly susceptible to brain damage in this model, while others (129Sv) are resistant.