Brain H ³ ‐catecholamine metabolism in experimental cerebral ischemia

Abstract

Unilateral ligation of a common carotid artery in gerbils causes a major depletion of brain dopamine, which is most marked in brain regions known to receive dopaminergic projections. To determine whether this depletion reflects release of stored dopamine, a radioactive label (H-3-dopamine) was introduced into brain dopamine pools 4 hours prior to ligation. Twenty-four hours later, brain H-3-catecholamines were profoundly depressed ipsilateral to the lesion among animals exhibiting clinical signs of stroke. Within brain regions known to receive dopaminergic projections, common carotid ligation also was associated with a selective decrease in the concentration of H-3-deaminated metabolites. These data suggest that cerebral ischemia is associated with release of catecholamines, as well as with impaired oxidative metabolism of catecholamines.

Histochemical changes of brain dopamine in an acute stage of cerebral ischemia in gerbils.

“…Since energy substances such as ATP, ADP and P-creatinine are more than half depleted in the ischemic cortex of gerbils, leakage of stored dopamine conceivable. Reports have also attributed the reduction of monoamine content in ischemic brain to a leakage or an increased release, 17 …”

Cathecholamine and 5-hydroxytryptamine levels in ischemic brain. Influence of p-chlorophenylalanine.

“…Other factors which would cause eventual intraneuronal monoamine depletion include failure of energydependent synaptosomal reuptake as well as synthesis impairment. 17 ' 2°D ecreased dopamine in nonoccluded hemispheres of symptomatic animals ( fig. 1) seems evidence of a remote effect of focal ischemia, i.e., diaschisis.…”

Partial reversal of asymmetry in microvessel neurochemical changes after ischemia by corpus callosum section.

“…Both neurotransmitter function and metabolism appear altered in various cerebral areas after ischemia.1-)2 These events are accompanied by changes in microvascular functions such as increased permeability to water and decreased glucose uptake and oxygen consumption. [3][4][5][6][7][8][9][10][11][12][13][14][15][16] Recent publications have demonstrated the existence of f3-adrenergic receptors coupled to adenylate cyclase in cerebral capillaries, which seem to be involved in the regulation of microvascular function. [17][18][19][20][21][22][23][24] In a previous study we investigated the effect of common carotid occlusion on f3-adrenergic receptor function in preparations of cerebral capillaries obtained from gerbils and rats.25' 26 The results indicated a significant decrease in the number of 8-adrenergic receptors in brain microvessels of both the ipsilateral and contralateral hemispheres.…”