Growth and development of brain of artificially reared hypoketonemic rat pups.

Three groups of rats were reared: mother-reared controls; artificially reared controls (AR-c), which were fed a milk substitute with the same composition of macro-nutrients as natural rat's milk; and an artificially reared test group (AR-h), which was fed a milk substitute identical to that fed AR-c pups except that the component of fat containing medium chain length fatty acids was omitted (medium chain triglyceride deficient) and replaced on an isocaloric basis with carbohydrate. The AR rats were fed the milk substitute from postnatal Day 5 until Day 17 by fitting them with gastric cannulas through which the milk could be infused automatically. The nutritional impact of the milk substitutes on growth and the integrity of the brain was assessed by a comparison of morphologic and biochemical markers. Pups in the AR-h group were hypoketonemic. Animals in all groups attained the same body weight by Day 17 and there was no difference in the morphologic markers among the groups with one exception: the vibrissal "barrel fields" of the somatosensory cortex of rat pups in both AR groups were reduced in size but not in number of distribution from those of the mother-reared groups. Furthermore, the brains of the rat pups in the AR groups were not different in weight, but they weighed less than brains of mother-reared controls. Our data show that although there are many similarities in the status of AR rat pups when compared with mother-reared controls, distinctive differences associated with artificial rearing are evident. We conclude that medium chain fatty acids in milk fat and the circulating ketone bodies are not mandatory substrates for growth and the development of the brain. Mechanisms must exist whereby alternative substrates are used to compensate when these metabolites are diminished in supply.