Introduction: Previous studies have demonstrated a profound dysfunction of cerebral metabolism following traumatic brain injury (TBI). Despite overall depression of cerebral metabolism, the cerebral metabolic rate (CMR) of oxygen is depressed out of proportion to the mildly reduced CMRglucose. This mismatch has raised the question, where does the missing glucose go if not metabolized oxidatively? We have previously demonstrated that an increased proportion of glucose is shunted through the pentose phosphate pathway prompting us to further investigate the total percentage of glucose metabolized by alternative pathways (the “missing glucose”) in an attempt to understand the full milieu of altered or dysfunctional metabolism in injured brain.

Methods: To determine CMR for oxygen, glucose & lactate by a modified Kety-Schmidt method, daily arterial and jugular venous blood samples and cerebral blood flow measurements were made in 74 moderate and severe TBI patients over the 1st 6 days post-injury. Data was also collected from 35 normal subjects. Using molar units, missing glucose utilization was calculated by CMRglucose(missing)=GMRglucose(total)-(CMRO2/6)+(CMRlactate/2) and converted to a percentage as CMRglucose(missing)%=(CMRglucose(missing)/CMRglucose(total))x100 (Dalsgaard et al. 2004). Overall trauma-normal differences were compared using a mixed effects model with random subject effect to account for the repeated measurements in the trauma group.

Results: The average calculated missing glucose (proportion of alternative glucose metabolism, not accounted for by oxidative metabolism or lactate production) was 34.45% in TBI subjects compared to 12.18% in normals (p=0.004). Overall CMRO2 (0.599 vs. 1.391; p<0.001), CMRglucose (0.193 vs. 0.296; p<0.001) and metabolic ratio (3.92 vs. 4.93; p=0.006) were all depressed in TBI subjects.

Conclusions: In addition to an overall depression of cerebral metabolism for oxygen and glucose, the percentage of glucose with alternative metabolic fates (missing glucose) was significantly higher in the post-traumatic brain compared to normal, almost a 3-fold elevation. Further study is needed to fully identify the alternative metabolic pathways involved.

Patient Care: Our characterization of the metabolic changes in the injured brain will help to understand the dysfunction that may lead to secondary injury following TBI. In the future, we hope that understanding this altered metabolism will aid in developing therapies to improve cerebral metabolism and limit secondary injury, maximizing recovery following TBI.

Learning Objectives: By the conclusion of this session, participants should be able to: 1) Identify the observed alterations in cerebral glucose metabolism following traumatic brain injury. 2) Discuss the implications of dysfunctional glucose metabolism to cerebral injury and outcome following TBI. 3) Discuss further studies to identify the specific alternative fates of glucose consumed by the brain.

References: Dalsgaard MK, Ogoh S, Dawson EA, Yoshiga CC, Quistorff B, Secher NH. Cerebral carbohydrate cost of physical exertion in humans. Am J Physiol Regul Integr Comp Physiol, 287(3):R534-40, 2004.