Excitotoxicity and metabolic changes in association with infarct progression

Abstract

Background and purpose: We investigated to what extent excitotoxicity and metabolic changes in the peri-infarct region of patients with malignant hemispheric stroke are associated with delayed infarct progression.

Methods: In 18 patients with malignant hemispheric stroke, 2 microdialysis probes were implanted within the peri-infarct tissue at a distance of 5 and 15 mm to the infarct. Precise probe placement was achieved by intraoperative laser speckle imaging. Glutamate, glucose, pyruvate, and lactate levels were monitored for 5 days after surgery. Delayed infarct progression was determined from serial MRI on the day after surgery and after the monitoring period.

Results: Initial stroke volume ranged from 122 to 479 cm3 with a median of 295 cm3. Nine of 18 patients (50%) had delayed infarct progression (median, 44 cm3; range, 19-93 cm3). In these patients, glucose and individual pyruvate levels were significantly lower when compared with patients without infarct progression, whereas glutamate and the lactate-pyruvate ratio were significantly elevated in patients with infarct progression early after surgery (12-36 hours) at the 15-mm microdialysis probe location. Lactate was elevated but without difference between groups.

Conclusions: Excitotoxic or metabolic impairment was associated with delayed infarct progression and could serve as a treatment target.

Keywords: glutamic acid; metabolism.