Prevention of developmental disorders of intra-uterine growth retarded infants with growth factors.

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The aim of this study is to determine the effect of undernutrition-induced intra-uterine growth retardation (IUGR) on the development of myelination and to clarify the role of insulin-like growth factor (IGF)-1 in the developing brain.Combination of the starvation of dams between embryonic day 17〜20 and restriction of feeding time of pups between birth〜postnatal day (P) 7 caused severe IUGR, resulting significantly lighter body weight up to P20. In this IUGR model, we investigated the expression levels of myelin-forming proteins, myelin basic protein (MBP) and proteolipid protein (PLP), using western blot analyses. MBP levels decreased to 58% in cerebral cortex and to 41% in cerebellum on P12, however they recovered to control level on P15. In striatum there was no decrease in MBP level. On the other hand, the expression levels of PLP did not decrease but increased to more than 200% of control group. PLP is more primitive in view of differentiation than MBP, which may result in their different expressions in IUGR brain.Intra-ventricular administration of IGF-1 on P7 accelerated the increase of MBP on P12. 5μg of IGF-1 was enough to recover MBP level in cerebral cortex and 10μg was necessary in cerebellum. On P15 any accelerating effect of IGF-1 on the expression of MBP and PLP was not observed.In conclusion IUGR causes insufficient forming of myelin sheath in cerebrum and cerebellum, which may lead to neurological sequelae in IUGR infants. IGF-1 may have a key role in achieving appropriate myelin formation in under-nutritional condition.