Increase of interstitial glycerol reflects the degree of ischaemic brain damage: a PET and microdialysis study in a middle cerebral artery occlusion-reperfusion primate model

摘要

OBJECTIVE—To evaluateinterstitial glycerol as a marker of ischaemia by studying the changesin glycerol in direct relation to changes in regional cerebralmetabolic rate of oxygen (CMRO2), the lactate/pyruvate ratio (LP ratio), and glutamate.
METHODS—Transorbital 2 hour middle cerebral artery occlusion (MCAO) was performed in eightmonkeys, which were studied with continuous microdialysis for 24 hours.Interstitial fluids were collected by microdialysis and analysed forglycerol, lactate, pyruvate, and glutamate with an enzymatic assay andhigh performance liquid chromatography. Sequential PET studies ofcerebral blood flow (CBF), CMRO2, oxygen extraction ratio(OER), and cerebral blood volume (CBV) were performed. Themicrodialysis probe regions were classified as severe ischaemia orpenumbra, depending on whether the mean CMRO2 side to sideratio was below or above 60%, respectively.
RESULTS—A nine-fold,sustained increase in glycerol was registered after MCAO in severeischaemia regions. In penumbra regions, the increase in glycerol wasfive-fold, but the glycerol concentration returned to baseline within 8 hours of clip removal. The difference between severe ischaemia andpenumbra glycerol values was statistically significant. As expectedfrom previous studies, the interstitial LP ratio and glutamateincreased markedly in severe ischaemia, with a less pronounced changein penumbra regions. There was a time lag between the biochemicalchanges in severe ischaemia regions, with the LP ratio precedingglutamate, followed by glycerol.
CONCLUSIONS—A marked,sustained increase in interstitial glycerol is indicative of severeischaemia in this stroke model. A transient, diminutive increase ininterstitial glycerol may reflect a penumbra situation. Interstitialglycerol in combination with other biochemical markers such as the LPratio and glutamate may be useful for clinical monitoring of theischaemic brain, reflecting a sequence of secondary pathophysiological events.