S.W. De Souza

Cerebral edema in developing brain: I. Normal water and cation content in developing rat brain and postmortem changes

Abstract In preparation for an experimental study of cerebral edema in immature brain, the normal development of rat brain has been studied with respect to brain weight, water, sodium, and potassium content from 16 days of gestation at frequent intervals until adult life. The time course of postmortem alteration of these values has been followed until 96 hr after death in the hope that brains from human autopsy may be assessed for the presence of edema. It has been noted that considerable alterations of composition occur at those stages of brain development corresponding to the perinatal period in humans. The significance of these, and of the differences between immature and mature brain, for the assessment of cerebral edema in babies is discussed.

FREE AND BOUND TRYPTOPHAN IN HUMAN PLASMA DURING THE PERINATAL PERIOD

Abstract. The concentration of tryptophan and the degree of binding of the amino acid to protein were examined in human plasma during the perinatal period. Both total and unbound (free) tryptophan were higher in cord vein plasma than in the maternal circulation, the concentration gradient being approximately 1: 2. The proportion of the total plasma tryptophan concentration that was not bound to protein was less in cord vein plasma than in the maternal circulation. After birth the proportion in infant plasma fell significantly. Both total and free tryptophan fell during the first 24 hours of postnatal life. Total tryptophan returned to the cord vein plasma level 6–8 days after birth whilst free tryptophan failed to increase during the period of the observations. In premature infants total and free tryptophan also declined in concentration 12–24 hours after birth, suggesting the phenomenon to be related to birth rather than to gestational age. Phenylalanine remained unchanged whilst tyrosine increased in concentration during the first 80 hours of postnatal life. Thus, the availability of tryptophan to the tissues appears to decline during the immediate postnatal period and the results suggest that the requirement for tryptophan during this time may exceed the supply from standard artifical milk preparations.

Cerebral Oedema in Developing Brain

Five-day-old rats subjected to prolonged asphyxia at body temperature (37 °) developed brain oedema as measured by increase in brain water and an increase in brain Na+/K+ ratio.

Influence of Asphyxia and of Dexamethasone on ATP Concentrations in the Immature Rat Brain

Five-day-old rats subjected to prolonged asphyxia (at 37 °C) to the point of death showed an approximately 50-percent loss of brain ATP and a rise in ADP and AMP. Brain energy charge was reduced from 0.86 to 0.64. Recovery of ATP levels to normal was virtually complete 20 min after beginning resuscitation. Rats treated with dexamethasone (20 mg/kg body weight) showed, during asphyxia, a fall in brain ATP which was significantly less than in those animals asphyxiated without steroid. Possible implications for the use of glucocorticoid therapy in asphyxia neonatorum are discussed.

Cerebral edema in developing brain: II. Asphyxia in the five-day-old rat

Abstract Five-day-old rats dying during prolonged asphyxia at body temperature (37 C) were found to have a metabolic form of brain damage (increase in brain [ Na + ] [ K + ] ratio) and brain edema (increase in brain water). Five-day-old rats dying during acute anoxia at body temperature had the same metabolic form of brain damage but not brain edema. Following prolonged asphyxia, metabolic damage was greater in brain stem as compared with forebrain or cerebellum. The presence of brain edema could be related to the severity of brain metabolic damage. During prolonged asphyxia the severity of metabolic brain damage was increased by pretreatment with sodium iodoacetate. Asphyxia at body temperature had a more damaging effect on the brain as compared with asphyxia at room temperature (22–24 C). Asphyxia in the presence of a carbon dioxide absorbant (soda lime) did not alter the severity of metabolic brain damage. It could be speculated that the human neonatal brain may undergo similar changes following birth asphyxia.

Effects of growth retardation and asphyxia on brain electrolytes and on glycolysis in developing rats.

Extract: During postnatal brain development in the rat there is a progressive decrease in the Na+/K+ ratio, which correlated with increasing activity of Na+-K+-activated ATPase. Undernutrition during intrauterine and early postnatal development (4–6 days) did not alter the Na+/K+ ratio, although there was a deficit in brain weight. However, undernutrition during the suckling period retarded the progressive fall in Na+/K+ ratio and rise in ATPase activity. The altered Na+/K+ ratio in these animals did not appear to be caused by change in brain carbohydrate metabolism.Developing rats undernourished until 4–6 days resembled the intrauterine growth-retarded human baby as regards deficits in body weight, relative sparing of the brain compared with other organs, and depleted carbohydrate reserves.The undernourished 4–6-day-old rat tolerated asphyxia as well as the well nourished rat of the same age. After asphyxia, the Na+/K+ ratio reverted to unity and there was an increase in brain water. Liver carbohydrate reserves did not appear to be a limiting factor that determined the point of death.Speculation: The normal gradients of Na+ and K+ between the cell and its environment in developing rat brain may be altered by asphyxia or undernutrition as a result of a defect in the Na+ pump mechanism. Such a defect may be caused by asphyxia at a time in rat brain development equivalent to that of the human brain in the perinatal period, i.e., in the first stages of the brain growth spurt. Undernutrition, however, may retard development of the Na+ pump only when its time of application includes the period of most rapid brain growth and maturation.

Some effects of acute anoxia and prolonged asphyxia on rat brain.

Abstract The effects of prolonged asphyxia at room temperature (22–24 C) and body temperature (37 C) and repeated acute anoxia at body temperature were studied in adult rats (10- to 18-weeks old). The effects of prolonged asphyxia at body temperature were also studied in young rats (4 weeks old). Rats dying during repeated acute anoxia at body temperature and prolonged asphyxia at room temperature showed an increase in brain sodium/potassium ratio only, whereas rats dying during prolonged asphyxia at body temperature also had an increase in brain water. Rats recovering from prolonged asphyxia at body temperature showed an increase in brain sodium/potassium ratio that was not present 4 hr later.