On-line monitoring of striatum glucose and lactate in the endothelin-1 rat model of transient focal cerebral ischemia using microdialysis and flow-injection analysis with biosensors

Abstract

In vivo studies on cerebral glucose and lactate metabolism following a brain insult require fast and sensitive monitoring techniques. Here we report on-line monitoring of ischemic events and metabolic changes following reperfusion in striatum of freely moving rats subjected to endothelin-1 (60-240 pmol) induced, transient focal cerebral ischemia using slow microdialysis (0.5 microl/min), fast sampling (every minute) and flow-injection analysis with biosensors for glucose and lactate. The high-time resolution provides detailed information on lactate rise times and duration of low glucose. In rats, developing large striatal lesions, lactate increased from 1.0 +/- 0.1 to 4.2 +/- 0.7 mM within 37 +/- 1 min, whereas glucose dropped from 0.3 +/- 0.1 mM to below detection levels (<0.05 mM) for a period of 80 +/- 18 min. The lactate increase measured over a 2-h period after endothelin-1 infusion was highly correlated with striatal infarct size. In some rats oscillatory changes are observed which cannot be detected in traditional assays. The here-described monitoring technique applied in a clinically relevant rat model is a sensitive tool to study post-ischemic energy metabolism, effects of therapeutic interventions and its relationship with histological outcome.