Periventricular leukomalacia (PVL) is the first cause of cerebral palsy in children surviving preterm birth. Surprisingly, PVL rate is very low in preterm infants born to mothers with pre-eclampsia. The mechanims of this protection against PVL are still unknown. We had previously described a neonatal murine model of cystic PVL produced by injection of ibotenate, a glutamatergic agonist. In the present study, we administered ibotenate to mice born to mothers with ligation of an uterine artery to determine if chronic in utero ischemia can protect newborn mice against excitotoxicity.

Pregnant mice were divided in 3 experimental groups: (1) permanent ligation of the left uterine artery at 13 days of gestation, (2) sham operated, (3) unoperated control mice. Mice were allowed to deliver at 19 days of gestation. In a first set of experiments ibotenate was injected in the right hemisphere at 2 days of postnatal age (P2) and mice were sacrificed at P5 for histological study (cresyl violet staining). In a second set of experiments, mice were sacrificed at P2 for immunohistochemical study of the astrocytes(GFAP staining). Pregnant mice were sacrificed at 18 days of gestation for placenta analysis. Only placentas with alive embryos were considered.The mean size of the litters (alive pups) was 7 in the group 1, 9 in the group 2 and 11 in the group 3. The mean weight of placentas was similar in each group. The mean weight of the mice at birth (without correcting for the reduced litter size) was also similar in each group. After ibotenate injection, mean size (+ sem) of cystic lesion was found smaller in group 1: 383 m (+ 75) versus 1109 m(+ 153) in group 2 and 887 m (+ 144) in group 3 (p < 0,01). The number of astrocytes at P2 in the periventricular area was slightly higher (+ 13%) in group 1 than in group 3 (p < 0,01). Moderate placental ischemic lesions were found in group 1.In conclusion, newborn mice born after in utero chronic ischemia are less sensitive to excitotoxic insult than controls. These data corroborate clinical observations. The mechanims of this protection against excitotoxicity remain unclear.