The brain
noradrenaline (NA) system is known to modulate ischemic neuronal damage, and the turnover of NA has been suggested to increase in the early recovery period following
cerebral ischemia. Using HPLC and gas chromatography-mass spectrometry we analyzed the tissue levels of NA and its metabolites, 3,4-dihydroxyphenylethyleneglycol (
DHPG) and 3-methoxy-4-hydroxyphenylethyleneglycol (
MHPG), in rat brain cortex after 10 min of forebrain
ischemia followed by 1 h of recirculation. The effect of
idazoxan, given in cerebro-protective doses, as a bolus of 0.1 mg.kg-1 immediately after
ischemia followed by 10 micrograms.kg-1.min-1 for 1 h, was also investigated.
Ischemia decreased basal NA cortical levels from 384 ng/g tissue in control animals to 214 ng/g, while
DHPG increased from 74 to 103 ng/g (+39%) and
MHPG from 82 to 154 ng/g (+88%). Conjugated but not free
DHPG increased, while both free and conjugated
MHPG increased equally. The findings indicate an enhanced postischemic NA turnover with a major proportion of uptake and metabolism occurring extraneuronally, possibly secondary to a saturation of neuronal NA uptake in the postischemic phase.
Idazoxan further increased NA turnover, as evidenced by higher postischemic levels of free
MHPG and a higher
MHPG/NA ratio. A correlation may exist between the protective action of
idazoxan and its effect on NA turnover.