Extracellular dopamine and serotonin in the rat striatum during transient ischaemia of different severities: a microdialysis study.
Generalised neurotransmitter overflow into the extracellular space on cerebral ischaemia has been widely reported and implicated in events leading to subsequent neuronal death. As little is known about the effect of depth of ischaemia on these changes, we have subjected anaesthetised rats to a sequence of four challenges [high K+ stimulus, moderate (penumbral) ischaemia, severe ischaemia, cardiac arrest] and have concurrently monitored both electrophysiological parameters and changes in extracellular dopamine, serotonin, and their metabolites in the striatum. Of particular relevance to human stroke therapy was penumbral ischaemia, where ionic homeostasis was maintained even though electrical function was lost. All challenges increased extracellular monoamines, although levels were significantly greater when ischaemia was severe enough to produce sustained anoxic depolarisation. Baseline levels were rapidly restored during recovery phases. Acidic monoamine metabolites decreased significantly during each insult, returning to basal levels during reperfusion after moderate ischaemia, and to significantly higher levels after severe ischaemia. Results indicate that sustained anoxic depolarisation may be a critical factor in determining outcome after ischaemia, being associated with significantly greater release of monoamines, and impairment of electrical function recovery.
Richards
D A
DA
Department of Neurochemistry, Institute of Neurology, London, England.
Obrenovitch
T P
TP
Symon
L
L
Curzon
G
G
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D003956:Dialysis / Q000379:methods; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism*; D004569:Electroencephalography; D005110:Extracellular Space / Q000378:metabolism*; D005260:Female; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000503:physiopathology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*
D012701:Serotonin; C001746:3-methoxytyramine; D011188:Potassium; D004298:Dopamine