Interstitial glycerol as a marker for membrane phospholipid degradation in the acutely injured human brain

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Abstract

Objective

Brain interstitial glycerol was studied as a potential marker for membrane phospholipid degradation in acute human brain injury.

Methods

Glycerol was measured in microdialysis samples from the frontal lobe cortex in four patients in the neurointensive care unit, during the acute phase after severe aneurysmal subarachnoid haemorrhage. Microdialysis probes were inserted in conjunction with a ventriculostomy used for routine intracranial pressure monitoring. Clinical events involving hypoxia/ischaemia were diagnosed by neurological signs, neuroimaging (CT and PET), and neurochemical changes of the dialysate-for example, lactate/pyruvate ratios and hypoxanthine concentrations.

Results

Altogether 1554 chemical analyses on 518 microdialysis samples were performed. Clinical events involving secondary hypoxia/ischaemia were generally associated with pronounced increases (up to 15-fold) of the dialysate glycerol concentration. In a patient with a stable condition and no signs of secondary hypoxia/ischaemia the glycerol concentration remained low. Simultaneous determination of glycerol in arterial plasma samples showed that the changes in brain interstitial glycerol could not be attributed to systemic changes and an injured blood brain barrier.

Conclusions

This study suggests that membrane phospholipid degradation occurs in human cerebral ischaemia. Interstitial glycerol harvested by microdialysis seems to be a promising tool for monitoring of membrane lipolysis in acute brain injury. The marker may be useful for studies on cell membrane injury mechanisms mediated by for example, Ca2+ disturbances, excitatory amino acids, and reactive oxygen species; and in the evaluation of new neuroprotective therapeutic strategies.

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