Abstract
The most important early pathomechanism in traumatic brain injury (TBI) is alteration of the resting membrane potential. This may be mediated via voltage, or agonist-dependent ion channels (e.g. glutamate-dependent channels). This may result in a consequent increase in metabolism with increased oxygen consumption, in order to try to restore ionic balance via the ATP-dependent pumps. We hypothesize that glutamate is an important agonist in this process and may induce an increase in lactate, potassium and brain tissue C02, and hence a decrease in brain pH. Further we propose that an increase in lactate is thus not an indicator of anaerobic metabolic conditions as has been thought for many years.
We therefore analyzed a total of 85 patients with TBI, Glasgow Coma Scale (GCS) < 8 using microdialysis, brain tissue oxygen, C02 and pH monitoring. Cerebral blood flow studies (CBF) were performed to test the relationship between regional cerebral blood flow (rCBF) and the metabolic determinants.
Glutamate was significantly correlated with lactate (p < 0.0001), potassium (p < 0.0001), brain tissue pH (p = 0.0005), and brain tissue C02 (p = 0.006). rCBF was inversely correlated with glutamate, lactate and potassium. 44% of high lactate values were observed in brain with tissue oxygen values, above the threshold level for cell damage.
These results support the hypothesis of a glutamate driven increase in metabolism, with secondary traumatic depolarization and possi- bly hyperglycolysis. Further, we demonstrate evidence for lactate production in aerobic conditions in humans after TBI. Finally, when reduced regional cerebral blood flow (rCBF) is observed, high dialysate glutamate, lactate and potassium values are usually seen, suggesting ischemia worsens these TBI-induced changes.