A. Pastuszko, METABOLIC RESPONSES OF THE DOPAMINERGIC SYSTEM DURING HYPOXIA IN NEWBORN BRAIN, Biochemical medicine and metabolic biology, 51(1), 1994, pp. 1-15
The purpose of this review is to describe the relationship between the
dopamine and amino acid neurotransmitter systems and cortical oxygen
pressure during different levels of cerebral hypoxia using newborn pig
lets as an animal model, adding new data from our laboratory. The extr
acellular dopamine increases as the oxygen pressure in the cortex decr
eases. The relationship between oxygen pressure and dopamine levels is
the same whether the hypoxia is induced by reduced FiO2 (high-how hyp
oxia) or by hypocapnia-induced cerebral vasoconstriction (Low-flow hyp
oxia). Thus it appears that, particularly in mild hypoxia, the extrace
llular level of dopamine depends primarily on the oxygen concentration
in the tissue with minimal influence of parameters such as blood flow
and pH. There is no ''oxygen reserve'' in the brain of newborn piglet
s and the extracellular levels of dopamine in the striatum increase al
most linearly with decrease in oxygen pressure, with even small decrea
ses in oxygen pressure resulting in increased dopamine levels. In cont
rast, the changes in extracellular concentrations of the excitatory am
ino acids glutamate and aspartate are variable and transient. In a maj
ority of 2- to 5 day-old piglets even very low oxygen pressures in the
brain did not result in significant alterations in the extracellular
levels of glutamate and aspartate. These changes in the dopaminergic s
ystem may contribute directly and indirectly to the neuronal damage th
at occurs during hypoxic/ischemic insult and reoxygenation in newborn
brain, particularly in the striatum. A variety of mechanisms are discu
ssed by which dopamine, in particular extracellular dopamine, can incr
ease cellular toxicity.