Relationships of Dopamine, Cortical Oxygen Pressure, and Hydroxyl Radicals in Brain of Newborn Piglets During Hypoxia and Posthypoxic Recovery

Abstract

The present study describes the relationships of extracellular striatal dopamine, cortical oxygen pressure, and striatal hydroxyl radicals in brain of newborn piglets during hypoxia and posthypoxic reoxygenation. Hypoxia was induced by reducing the fraction of inspired oxygen (Fi02) from 22% (control) to 7% for 1 h . The F i 02 was then returned to the control value and measurements were continued for 2 h. Cerebral oxygen pressure was measured by the oxygen dependent quenching of phosphorescence and extracellular levels of dopamine, 3,4dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and hydroxy radicals in the striatum were determined by in vivo microdialysis . Hypoxia decreased the cortical oxygen pressure from 47 ± 2 to 9 -1 .3 torr (p < 0.001) ; the levels of extracellular dopamine in the striatum increased to 16,000 ± 3,270% of control (p < 0.01), whereas the levels of DOPAC and HVA decreased to 25 .3 ± 6% (p < 0.001) and 36 ± 5% (p < 0.01) of control, respectively . Compared with control, the hydroxyl radical levels at each time point were not significantly increased during hypoxia, although the sum of the measured values was significantly increased (p < 0.05) . During the first 5 min after Fi 0 2 was returned to 22%, the cortical oxygen pressure increased to control values and stayed at this level for the remainder of the measurement period . The extracellular level of dopamine declined to values not statistically different from control during 40 min of reoxygenation. During the first 10 min of reoxygenation, DOPAC and HVA further decreased and then began to slowly increase . By 70 min of reoxygenation, the values were not significantly different from control. Hydroxyl radicals were above control during the entire period of reoxygenation, with maximal values observed after 100 min of reoxygenation. This increase was largely abolished by injecting the animals with a-methylp-tyrosine 5 h before hypoxia, a procedure that depleted the brain of dopamine. Our results suggest that oxidation of striatal dopamine during posthypoxic reoxygenation is at least partly responsible for the observed increase in striatal level of hydroxyl radicals that may exacerbate posthypoxic cerebral injury . Key Words: Hypoxia-Brain-Dopamine-Hydroxyl radicals-Newborn .

Intracellular PO2 of the Carotid Body

“…This fell to about 40 mm Hg when the arterial oxygen pressures were decreased to about 90 mm Hg (low normal). Both oxygen extraction and the resulting vascular oxygen pressures were similar to those found, for example, in brain cortex (Silver, 1977;Lubbers, 1994;Olano et al 1995). The oxygen pressures measured by phosphorescence quenching were more consistent with those of Whalen and Nair (1977;1983) as the extravascular oxygen pressures might be expected to be below those in the microcirculation by 5-10 mm Hg.…”

Hyperbaric oxygenation mitigates focal cerebral injury and reduces striatal dopamine release in a rat model of transient middle cerebral artery occlusion

“…This may explain the variable infarct size following MCAO (Derugin et al 1998). It has been shown that 7% hypoxia caused a gradual increase in the striatal DA release with achievement of peak concentrations after 60 min (Olano et al 1995). In addition, the site of the probe plays an important role in detecting the changes of DA release.…”

“…It has been hypothesized to result from the generation of free radicals, in particular in regions of the brain such as the striatum (Hallgren and Sourander 1958;Lei et al 1997;Olano et al 1995). 2.…”

“…Several mechanisms underlying the detrimental effect of excessive DA on neurons have been postulated. Oxidation of large amounts of DA promotes the generation of free radicals, in particular in regions of the brain such as the striatum (Hallgren and Sourander 1958;Lei et al 1997;Olano et al 1995). The generated free radicals can further oxidize DA, and the oxidized DA can form covalent bonds, which may cause a modification of protein structure and function, and consequently, damage the tissues (Tse et al 1976;Graham et al 1978;Graham 1984).…”

Effect of Moderate Hypercapnic Hypoxia on Cerebral Dopaminergic Activity and Brain O2 Uptake in Intrauterine Growth–Restricted Newborn Piglets

“…Furthermore, the reduced catabolism of DA by monoamine oxidase could be responsible for reduced clearance rates for FDOPA metabolites in piglets with IUGR during moderate H/H. Hypoxia caused a substantial decrease in the levels of 3,4-dihydroxyphenylacetic acid and homovanillic acid, two key metabolites of DA degradation in newborn piglet brain during severe hypoxic hypoxia (38).…”