Reduced number of neurons in the hippocampus and the cerebellum in the postnatal guinea-pig following intrauterine growth-restriction
Section snippets
Surgery
Plug-mated females were housed under standard conditions in a 12-h dark/light cycle, fed ad libitum with rabbit/guinea-pig pellets and water. Surgery was performed on 13 pregnant Dunkin–Hartley guinea-pigs from Monash University, at 28–30 days of gestation (term ∼ 68 days). Chronic placental insufficiency was induced by unilateral ligation of the maternal uterine artery as previously described.31 Briefly, the mesometrium of the right uterine horn was exposed via a midline incision and the
Neuronal counts
The optical fractionator44 was used to obtain estimates of total number of pyramidal neurons in the CA1 region of the hippocampus and Purkinje neurons in the cerebellum. This unbiased stereological method combines fractionator sampling and optical disector counting. Using this technique the number of neurons are systematically counted with the optical disector technique,17 within a known fraction of the selected brain region. For each animal, sections are selected at predetermined uniform
Development of the hippocampus and cerebellum in the fetus at 30 days gestation.
At the time of uterine artery ligation (30 days gestation) fetuses weighed 6.71±1.00 g and brain weights were 0.56±0.02 g, representing 5% and 16%, respectively of the weights at birth in the normal guinea-pig. The cerebellum appeared extremely immature and consisted predominantly of densely packed undifferentiated neurons (Fig. 1A). A band of cells, five to six cells in width, containing mitotic figures, comprized the external granular layer. A second band, three to four cells thick, was evident
Discussion
This study has demonstrated, using modern unbiased stereological techniques, that a period of reduced placental blood flow during the latter half of pregnancy can affect neuronal numbers in the hippocampus and the cerebellum in postnatal animals. Animals with growth restriction showed a reduction in the total number of CA1 pyramidal neurons in the hippocampus and in Purkinje neurons in the cerebellum. Furthermore, the volumes of specific fibre layers within these structures were reduced
Acknowledgements
The authors thank Jillian Craigie for her excellent assistance with preparation of histological sections and volume measurements in the hippocampus and Prof. John Bertram for his advice on stereology. This study was supported by the National SIDS Foundation of Australia and The Mental Health Research Institute, Melbourne.
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