Reduced number of neurons in the hippocampus and the cerebellum in the postnatal guinea-pig following intrauterine growth-restriction

Abstract

Intrauterine growth restriction is a risk factor for neurological and behavioural deficits in children although the precise underlying biological correlate for this is unclear. The present study shows that animals with intrauterine growth restriction, induced by a period of reduced placental blood flow during the second half of pregnancy, demonstrate reduced numbers of neurons in the hippocampus and the cerebellum in conjunction with retarded dendritic and axonal growth within these structures.Intrauterine growth restriction was induced at 30 days gestational age by unilateral uterine artery ligation in pregnant guinea-pigs. At one week of age, the total number of CA1 pyramidal neurons in the hippocampus and the Purkinje neurons in the cerebellum were determined using the combined fractionator/optical disector technique. The Cavalieri Principle was used to determine the volume of specific regions within the hippocampus and cerebellum. The body weight of animals that were classified as intrauterine growth-restricted was reduced by 42% (n=8) compared with control animals (n=8, P<0.001), while there was a smaller effect on brain weight (16% reduction, P<0.01). Estimates of the total number of neurons showed a reduction in CA1 pyramidal neurons in growth-restricted animals (4.19±0.43×105) compared with control (5.20±0.44×105, P<0.01), and the volume of the stratum oriens layer above the CA1 region, which contains the apical dendrites of the CA1 pyramidal neurons, was reduced by 21% (P<0.01) in growth-restricted animals. In the cerebellum there was a reduction in the number of Purkinje neurons in growth-restricted animals (3.97±0.50×105) compared with control (5.13±0.52×105, P<0.01), and in the volume of the molecular layer (17%, P<0.05), the internal granular layer (22%, P<0.01) and in the volume of the cerebellar white matter (23%, P<0.01).These results show that a period of placental insufficiency during the second half of pregnancy can effect brain development in a way which could lead to neurological and behavioural deficits in the postnatal animal.