Cerebral Function in the Gowth-Retarded Fetus and Neonate

Abstract

Intrauterine growth retardation is associated with increased risks for permanent neurological disabilities. A series of studies was undertaken to elucidate whether fetal growth retardation causes a primary perturbation of brain function and development and whether an increased vulnerability for periods of oxygen lack exists. In two groups of neonates who were small for gestational age (SGA) evoked potentials were investigated. A high frequency of abnormal recordings were obtained in SGA babies. SGA babies had significantly longer latency periods for the primary evoked potentials than appropriately grown controls. In guinea pigs and rats growth retardation was induced by reducing the placental blood flow during late gestation. Growth retarded guinea pups demonstrated a considerable reduction of the ability to retain normal somatosensory evoked response during hypoxia compared to appropriately grown littermates. Growth retarded rat fetuses exhibited marked changes of the monoamine metabolism in the brain inasmuch as basal levels of serotonin and its main metabolite were low while an inappropriate acceleration of the serotonin synthesis rate took place during hypoxia. The tissue concentrations of aspartate were also significantly lower in growth retarded fetuses than normally grown littermates. Finally, lipid peroxidation was assessed. During adequate oxygenation no difference was observed when lipid peroxidation was assessed. During adequate oxygenation no difference was observed when lipid peroxidation in brain tissue of growth retarded and appropriately grown fetuses was compared but during mild-moderate hypoxia lipid peroxidation was significantly more intense in the growth retarded group. In conclusion, studies on SGA babies bring forward primary consequences of growth retardation on cerebral function and animal studies provide evidence both for a deficiency of factors that support brain growth and for some mechanisms that may be related to a decreased tolerance towards oxygen deficiency.

Abnormal Retinal Optic Nerve Morphology in Young Adults after Intrauterine Growth Restriction

“…Growth-retarded fetal sheep had a disproportionate reduction in myelin of axons in the optic nerve, whereas the trochlear nerve was not similarly affected, suggesting alteration in oligodendrocyte activity in fetal growth restriction (18). Studies on visual evoked potential latencies in infants born SGA have shown conflicting results, reporting both prolonged and shorter latencies, suggesting alterations in myelination but in opposite directions (19,20). Studies using magnetic resonance imaging have shown signs of decreased or highly variable myelination in infants with IUGR (21,22).…”

5-HT2A/2C Receptor–Mediated Hypopnea in the Newborn Rat: Relationship to Fos Immunoreactivity

“…Notably, although apparently not primarily responsible for apnea in a normoxic environment, the activation of 5-HT 2 receptors might have a negative influence on the newborn's ability to recover from sustained apneic episodes when hypoxemia develops. This might increase the vulnerability of small-for-age neonates, which exhibit an inappropriate acceleration of serotonin synthesis during hypoxia (9). Furthermore, independent of the occurrence of hypoxic episodes, 5-HT 2 receptor activation might work together with altered respiratory muscle function (20) to impair ventilation in growth-retarded neonates with increased serotonin synthesis (8).…”

“…Indeed, the likelihood of 5-HT 2 receptors being activated increases with the concentration of serotonin synthesized or released centrally. This concentration has been reported to be abnormally elevated in neonates with intrauterine growth retardation (8) and notably during hypoxia (9). Furthermore, although serotonin acting at 5-HT 2 receptors might be benefi-cial to adults suffering from pathologic apneas in that it decreases the duration of deep slow-wave sleep (10), this mechanism might be inefficient in the neonate (11).…”

Effect of SOD-Mimetic Fe-Chlorine e6-Na on the Level of Brain Lipid Peroxide of Rat Fetal Brains Exposed to Reactive Oxygen Species Leading to Intrauterine Growth Retardation

“…Several reports [7][8][9] have provided evidence of a strong link between oxidative stress and brain damage.…”

“…Despite considerable information on the biochemical changes associated with hypoxia, a true understanding of the mechanisms leading to these changes has not been established. Recently some reports have suggested a strong link between oxidative stress and brain damage [6][7][8]. The brain is believed to be particularly vulnerable to Saito/Maeda/Yoshihara/Amano/Nishijima/ Nakamura oxidative damage due to the fact that it contains high concentrations of easily peroxidizable lipids, i.e., polyunsaturated fatty acids, has regions that are particularly enriched in iron, and has comparatively low to moderate levels of endogenous antioxidant molecules [9].…”