Age-dependent pathways of brain energy metabolism: the suckling rat, a natural model of the ketogenic diet.

As a consequence of the high fat content of maternal milk, the suckling rat may be viewed as a 'natural model' of the ketogenic diet. Changes in energy metabolism during this period of development may give us some clues into the antiepileptic properties of the ketogenic diet. We have, therefore studied the postnatal evolution of local cerebral metabolic rates for glucose (LCMRglcs) and of regional rates of cerebral uptake of beta-hydroxybutyrate (betaHB) in the developing rat between postnatal day (PN) 10 and 35. LCMRglcs were low and homogeneous at PN10. They increased significantly in four auditory regions between PN10 and PN14, at the time of maturation of auditory function. Between PN14 and PN17, they increased further in two auditory regions, one visual area (the lateral geniculate nucleus), three limbic and three motor areas. These increases occurred simultaneously with the maturation of vision and the development of locomotion and general exploratory behavior. Between PN17 and PN21, LCMRglcs increased by 28-97% (depending on brain area) and by a mean value of 25% in all areas studied. In contrast to the function-related increases in LCMRglcs, regional rates of cerebral betaHB uptake underwent a generalized non-specific increase between PN1O and PN14, and stayed at a high level until PN17. Between PN17 and PN21, rates of cerebral betaHB uptake decreased significantly in all brain regions studied, and reached very low levels by PN35. Thus, even in the suckling rat, whose cerebral metabolic activity depends upon both glucose and ketone bodies, it is the postnatal increases in LCMRglcs that appear to be critical for the acquisition of new functions and neurological competence. Conversely, the homogeneous increase in cerebral betaHB uptake occurring between PN10 and PN17 at a period of active brain growth may rather reflect non-specific mechanisms of cell growth.