Protein ubiquitination plays an important role in rapid degradation of short-lived, denatured or damaged proteins. Previous studies have postulated that ubiquitin expression is up-regulated in the brain after transient global ischemia (Caray et al, 1995). The present study was designed to compare the expression of ubiquitin mRNA level in the fetal sheep brain under conditions of acute cerebral hypoxic ischemia or IUGR induced by 4 to 5 weeks of chronic hypoxia from single umbilical artery ligation. We examined the brains from nine fetal sheep in three different groups: Group 1 (N=3), Fetuses in which single umbilical artery ligation resulted in IUGR. Group 2 (N=3), Fetuses with HIE induced by transient carotid artery occlusion. Group 3 (N=3), control intact fetuses. Haematoxylin-Eosin staining was utilized to confirm histopathologic neuronal injury. mRNA levels were measured by conventional PCR and read by phospho-imaging utilizing Cyber Green II. Statistical comparisons between groups was done by the Wilcoxon rank non-parametric test.

Results: Animals from group 1 and 2 showed generalized cortical neuronal injury with significant loss of temporal layer structuring.

Conclusions: Single umbilical artery ligation resulted in neurologic injury similar to the injury seen in HIE after transient carotid artery occlusion. The levels of brain ubiquitin mRNA appear to be higher in the HIE and IUGR groups when compared to those seen in the control group; additional animals are currently being evaluated. These preliminary observations suggest that Ubiquitin up-regulation may occur in the brain of fetal sheep after single umbilical artery ligation or carotid occlusion which results in neurologic injury. Table 1

Table 1 Brain Polyubiquitin mRNA levels (expressed in arbitrary density units normalized to 4.7 μg/μl of mRNA; Mean + Standard Deviation.
Full size table