Activity of Tyrosine Hydroxylase in the Striatum of Newborn Piglets in Response to Hypocapnic Hypoxia

Abstract

The effect of graded hypoxia induced by hyperventilation on the activity of tyrosine hydroxylase was measured in vivo by microdialysis. Microdialysis probes were inserted into the striatum of newborn piglets and perfused with medium containing 3-hydroxybenzylhydrazine, an inhibitor of L-aromatic amino acid decarboxylase. The level of 3,4-dihydroxyphenylalanine (DOPA) measured in the effluent dialysate was then an index of tyrosine hydroxylase activity. The oxygen pressure in the veins and capillaries of the cortex was measured, through a cranial window placed over the parietal cortex, by the phosphorescence lifetime of palladium-meso-tetra(4-carboxyphenyl)porphine added to the blood. After baseline measurements, PaCO2 was decreased from 38 torr (control value) to 19, 13, and 11 torr resulting in decreases in the cortical oxygen pressure from 40 +/- 6 torr to 26 +/- 3, 23 +/- 4, and 20 +/- 4 torr, respectively. Decrease in the oxygen pressure to 26 +/- 3 torr caused a statistically significant increase of 25-30% in the level of DOPA in the effluent perfusate. During the next step of increase in ventilator rate, when oxygen decreased only slightly, the level of DOPA remained at the higher level. Ventilation rates that lowered the oxygen pressure to below 20 torr, however, caused a progressive decrease in the level of DOPA. During recovery, the level of DOPA steadily increased, attaining 160% of control value after 1.5 h. When the oxygen pressure was decreased to 16 +/- 2 torr by a single increase in ventilator rate, the DOPA level decreased in the effluent to 15-20% below control.(ABSTRACT TRUNCATED AT 250 WORDS)

A Piglet Model of Neonatal Hypoxic-Ischemic Encephalopathy

“…Piglet model studies played a key role in establishing hypothermia as a treatment for HIE 21 , and are used in neonatal resuscitation research 22 . Various groups have used piglet models when performing research within asphyxia and HIE, and studies include hypothermia 23 , alpha-melanocyte-stimulating hormone 24 , cardiac arrest 25 , tyrosine hydroxylase activity 26 , repeated hypoxic exposure 27 , NMDA receptor activity 14 , and near-infrared spectroscopy 28 . The piglet HIE model presented in this report is technically challenging to work with, as minor adjustments during the course of the procedure may result in either too mild or too severe brain injury 29,2 .…”

Rethinking Parkinson's disease: could dopamine reduction therapy have clinical utility?

“…Unilateral striatal injection of 6-hydroxydopamine in rats increases specific activity of tyrosine hydroxylase locally but not in the contralateral striatum [37], as if it were a compensatory response to the local toxic injury within the striatum. Similarly, when newborn pigs were exposed to mild hypoxia, dopaminergic synthesis rose and continued to do so after cessation of hypoxia, to ~ 140% of baseline level [38], consistent with a compensatory response to the ischemic injury to the striatum. Thus, two types of acute striatal injuries lead to increased dopamine synthesis, suggesting the possibility of its role as an early contributor to disease.…”

Correspondence

“…Of course, these white matter echolucencies related to so-called "late-onset PVL" can not be associated with hypocarbia during the 1st day of life. In addition to clinical studies, normoxic or hypoxic hypocarbia has been demonstrated to augment neonatal cerebral injury in different animal species underlining the potentially deleterious effects of hypocarbia (17,18). Which conclusions can be drawn from the study by Dammann et al?…”