The Effects of Age and Ketogenic Diet on Local Cerebral Metabolic Rates of Glucose after Controlled Cortical Impact Injury in Rats

Abstract

Previous studies from our laboratory have shown the neuroprotective potential of ketones after TBI in the juvenile brain. It is our premise that acutely after TBI, glucose may not be the optimum fuel and decreasing metabolism of glucose in the presence of an alternative substrate will improve cellular metabolism and recovery. The current study addresses whether TBI will induce age-related differences in the cerebral metabolic rates for glucose (CMRglc) after cortical controlled impact (CCI) and whether ketone metabolism will further decrease CMRglc after injury. Postnatal day 35 (PND35; n = 48) and PND70 (n = 42) rats were given either sham or CCI injury and placed on either a standard or a ketogenic (KG) diet. CMRglc studies using (14)C-2 deoxy-D-glucose autoradiography were conducted on days 1, 3, or 7 post-injury. PND35 and PND70 standard-fed CCI-injured rats exhibited no significant neocortical differences in CMRglc magnitude or time course compared to controls. Measurement of contusion volume also indicated no age differences in response to TBI. However, PND35 subcortical structures showed earlier metabolic recovery compared to controls than PND70. Ketosis induced by the KG diet was shown to affect CMRglc in an age-dependent manner after TBI. The presence of ketones after injury further reduced CMRglc in PND35 and normalized CMRglc in PND70 rats at 7 days bilaterally after injury. The changes in CMRglc seen in PND35 TBI rats on the KG diet were associated with decreased contusion volume. These results suggest that conditions of reduced glucose utilization and increased alternative substrate metabolism may be preferable acutely after TBI in the younger rat.