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.
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.
Gramsbergen
Jan Bert
JB
Anatomy and Neurobiology, Institute of Medical Biology, University of Southern Denmark, Odense, Denmark. jbgramsbergen@health.sdu.dk
Skjøth-Rasmussen
Jane
J
Rasmussen
Camilla
C
Lambertsen
Kate Lykke
KL
D000818:Animals; D015374:Biosensing Techniques / Q000379:methods*; D002544:Cerebral Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000009:adverse effects; D004734:Energy Metabolism / Q000502:physiology; D017022:Flow Injection Analysis; D005947:Glucose / Q000032:analysis* / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019344:Lactic Acid / Q000032:analysis* / Q000378:metabolism; D008297:Male; D017551:Microdialysis / Q000295:instrumentation / Q000379:methods*; D009448:Neurochemistry / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012815:Signal Processing, Computer-Assisted; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D019332:Endothelin-1; D019344:Lactic Acid; D005947:Glucose