Reemphasis of the Role of 5-Hydroxytryptamine in Cerebral Ischemia
Cortical monoamine changes during ischemic episodes of up to one hour were studied in the gerbil. Norepinephrine (NE) levels decreased after 60 minutes in the occluded hemisphere of animals with stroke, but dopamine (DA) levels were unaltered. 5-Hydroxytryptamine (5-HT) levels became bilaterally reduced in animals with and without stroke as soon as 5 minutes after occlusion. Abnormal motor activity suggestive of seizure developed in some animals that exhibited signs of stroke. Accordingly, the influence of seizure activity on cortical monoamine changes was studied in a second experiment. Reduction of DA and NE was only observed when seizures occurred in association with stroke. 5-HT levels were reduced bilaterally in animals with and without signs of stroke and reduced further in animals with stroke plus seizure. We concluded that seizure activity must be taken into account when examining the mechanism of disordered catecholamine metabolism in the gerbil stroke model. However, 5-HT metabolism appears disordered in ischemic brain independent of seizure activity.
It was in 1971, after observing 5-hydroxytryptamine release from brain into cerebral venous blood during acute ischemia in the primate, that we first confirmed a suspected disorder of monoamine neurotransmitter metabolism in the pathogenesis of stroke (18) and subsequently performed experiments which indicated that the vasoconstrictor effect of 5-hydroxytryptamine release onto intraparenchymatous cerebral vessels in ischemic brain foci might be responsible for impairment of potential collateral circulation and for progression of ischemia (17). Since this time, reports from a number of workers who have studied prolonged ischemia in the gerbil have emphasized alterations in catecholamine metabolism, particularly dopamine, as a contributing factor to the pathogenesis of stroke (5, 9, 20). Although our own studies in the gerbil also revealed catecholamine depletion in brain cortex after prolonged ischemia (16), two recent studies reported here and in part elsewhere (1, 19) have served to emphasize more the role of 5-hydroxytryptamine changes, particularly during brief and transient cerebral ischemia.
KeywordsCerebral Ischemia Seizure Activity Right Hemisphere Transient Cerebral Ischemia Brain Monoamine
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