Citation

Hinzman J, Wilson JA, Mazzeo AT, Bullock R, Hartings JA. J. Neurotrauma 2015; 33(19): 1775-1783.

Affiliation

University of Cincinnati, Dept of Neurosurgery , 260 Stetson St. Suite 2200 , Cincinnati, Ohio, United States , 45219 , office: 513-558-3567 ; hartinja@ucmail.uc.edu.

Copyright

(Copyright © 2015, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2015.4226

PMID

26586606

Abstract

Cerebral microdialysis has enabled the clinical characterization of excitotoxicity (glutamate > 10 µM) and non-ischemic metabolic crisis (lactate/pyruvate ratio, LPR > 40) as important components of secondary damage in severe traumatic brain injury (TBI). Spreading depolarizations (SD) are pathological waves that occur in many patients in the days following TBI and, in animal models, cause elevations in extracellular glutamate, increased anaerobic metabolism, and energy substrate depletion. Here, we examined the association of SD with changes in cerebral neurochemistry by placing a microdialysis probe alongside a subdural electrode strip in peri-lesional cortex of 16 TBI patients requiring neurosurgery. In 107 hr (median; range: 76-117) of monitoring, 135 SDs were recorded in 6 patients. Glutamate (50 µmol/l) and lactate (3.7 mmol/l) were significantly elevated on day 0 in patients with SD compared to subsequent days and to patients without SD, while pyruvate was decreased in the latter group on days 0 and 1 (Two-way ANOVA's, P's<0.05). In patients with SD, both glutamate and LPR increased in a dose-dependent manner with the number of SDs in the microdialysis sampling period (0, 1, ≥2 SD) [glutamate: 2.17.052.3 µmol/l; LPR: 27.829.945.0, P's<0.05]. In these patients, there was a 10% probability of SD occurring when glutamate and LPR were in normal ranges, but a 60% probability when both variables were abnormal (>10 µmol/l and >40, respectively). Taken together with previous studies, these preliminary clinical results suggest SDs are a key pathophysiological process of secondary brain injury associated with non-ischemic glutamate excitotoxicity and severe metabolic crisis in severe TBI patients.

Language: en