It has been reported that ischemia causes changes in the concentration and turnover of monoamine neurotransmitters in brain. For the mechanism of cellular death in grain ischemia it is suggested that accumluation of intracellular calcium during
ischemia
is one of the main causes. Present study was undertaken to investigate the influence of isohe mia on the contents and turnover of the biogenic amines in rat brain and further to investigate the effects of nimodipine, a calcium channel bllocker,
and
cromakalim, a potassium channel opener, on them Brain ischemia was induced by partial ligation of bilateral common carotid artery. Nimodipine (36μg/kg, i.p.) or cromakalim (0.5mg/kg, i.p.) was administerd 20 minutes before ligation. Nimodipine
was
administered every 4 hours in 24-hour ischemic group. Rats were sacrificed by decapitation 3 or 24 hours after induction of ischemia and whole brains were excised. The brain was divided into following regions; cerebral cortex, corpus striatum,
hippocampus, thalamus, hypothalamus, sudlites were measured by high performance liquid chromatography-electrochemical detector (HPLC-ECD).
The results obtained are as follows ;
1. the contents of 5-HT and 5-HIAA, and norepinephrine were highest in the substantia nigra and hypothalamus of normal brain, respectively. Both DOPAC and HVA were detected in corpus striatum.
2. The 5-HT content was decreased to one half of control in the frontal cortex of 3hour ischemic brain, which was mostly prevented by nimodipine treatment.
3. The norepinephrine content was decreased in the frontal cortex, hippocampus and thalamus of 3 hour ischemic brain. The dopamine content was decreased in the corpus striatum. These changes were prevented by nimodipine treatment.
4. The turnover rate of 5-HT and norepinephrine in 3-hour ischemic brain were in creased in frontal cortex and hippocampus, and in the corpus striatum, respectively. These changes were prevented by nimodipine.
5. Cromakalim had Iittle effect on the content or turnover rate of biogenic amines in 3-hour ischemic brain except frontal cortex.
6. In 24-hour ischemic group, the changes of biogenic amines were minmal other than the increase of 5-HIAA of frontal cortex, corpus striatum, hippocampus and thalamus.
7. The activity of ischemic rat was decreased, which was recovered by nimodipine.
8. the mortality of ischemic rat within 24 hour was 33.35 and it was reduced significantly by cromakalim.
Based on these results, it is concluded that the changes in concentration of biogenic amines and their turnover rate of the ischemic brains are prominent within 3 hour of ischemia and these changes are mostly attenuated or prevented by calcium
channel
blocker nimobipine, so it is belideved that the increase of calcium influx during ischemia is one of the main cause of these changes.
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