Effect of cerebral ischemia on synaptosomal uptake and release of 3H-5-hydroxytryptamine in adult and young Mongolian gerbils.

Cerebral ischemia induced by bilateral common carotid artery occlusion (15 min) with and without release (1 hr) served as a model for comparative regional studies of synaptosomal 3H-5-hydroxytryptamine (3H-5-HT) uptake and release in adult and young gerbils. A decreased uptake and an increased release of 5-HT was observed in the adult after ischemia alone and/or ischemia with reflow. At the same time, 5-HT uptake was not affected except in the cortex and the release was reduced in the young. These findings indicate that the same ischemic insults affect differently the synaptosomal uptake and/or release of 5-HT in adult and young brain.

Cerebrocortical modulation of S2-receptors and turnover rate of 5-hydroxytryptamine in ischemia.

A possible relationship between the changes in the properties of S2-receptor binding sites and the turnover rate of 5-hydroxytryptamine (5-HT) has been investigated in cerebral ischemia associated with either little or marked edema. Bilateral common carotid artery occlusion for 5 or 15 min with 1 hour of reestablished blood flow in gerbils served as a model for the respective studies. An alteration in kinetic characteristics of S2-receptor binding sites labeled with [3H]ketanserin (the potent 5-HT antagonist for postsynaptic receptors) was detected in the synaptosomes separated from brains of gerbils subjected to 1 hour release after 15 but not following 5 min of bilateral ischemia. At the same time, an increased turnover rate of 5-HT was found in the cerebro-cortical homogenate. The duration of ischemic insult which leads to the changes in the properties of S2-binding sites and the increase in turnover rate of 5-HT has been identical with that needed for the marked accumulation of water in the gerbil brain reported previously. Thus, these findings are consistent with the implicated involvement of 5-HT in the formation of ischemic cerebral edema.

Catecholamine turnover in rat cerebral cortex and caudate following repeated treatment with dihydroergotoxine.

The turnover rate of catecholamine in the cerebral cortex and caudate of adult Wistar rats was estimated after inhibition of synthesis by means of alpha-methyl-rho-tyrosine in animals treated with dihydroergotoxine (1 mg/kg body weight daily) for 1, 3 and 10 days. Following single as well as repeated treatments with the drug, blockade of norepinephrine receptors, as indicated by the increased catecholamine turnover rate, was found in both brain structures. The turnover rate of dopamine was changed only after repeated treatments; it was decreased in the cortex and increased in the caudate, indicating both agonistic and antagonistic effects of dihydroergotoxine on dopamine receptors.

Monoamines and related enzymes in cerebral cortex and basal ganglia following transient ischemia in gerbils.

The post-ischemic effects on cerebral cortex and basal ganglia monoamine levels and monoamine oxidase (MAO A and B) and catechol-O-methyl transferase (COMT) activities were evaluated in Mongolian gerbils (Meriones unguiculatus) subjected to bilateral common carotid arteries of occlusion for 15 min and reflow for 7 days. Disorders of monoamine metabolism was found in ischemic brain which persisted during the long-term post-ischemia. A rebound increase of norepinephrine and serotonin appeared in early stages (up to 1 h) of post-ischemia both in cerebral cortex and basal ganglia; a rebound increase of dopamine as found only in cerebral cortex. Thereafter, the serotonin level ws enhanced over the control level during the whole post-ischemic period whereas the levels of catecholamines were reduced particularly in basal ganglia. With respect to monoamine content and activities of monoamine degraded enzymes an oscillatory behavior was observed in the post-ischemia. Disorder of the monoamine metabolism found during post-ischemic period possibly contributes to neurological dysfunction after an ischemic insult.

Alterations of putative neurotransmitters and enzymes during ischemia in gerbil cerebral cortex.

Bilateral occlusion of common carotid arteries in Mongolian gerbils was produced for the periods (up to 15 min) which were shown to be totally reversible. There was an initial increase of cyclic AMP and GABA levels and enhanced activities of adenylate cyclase and glutamate decarboxylase, as well as the reduction of norepinephrine level and decreased activities of monoamine oxidase, GABA-transaminase and Na+-K+-ATPase. Following these changes, decreased concentration of dopamine, serotinin and glutamate were found. The activities of total protein kinase and acetylcholinesterase were found to be reduced after longer periods of short-term ischemia. The data are consistent with the concept of increased non-controled release of putative neurotransmitters in ischemia.