Abstract
Recently, theophylline has increasingly been used for prevention of apneic spells in premature infants. However, there is a concern about the effect of theophylline on the developing brain in the perinatal period. In this report, we studied biochemical changes in fetal brain of rabbits, whose mothers had been treated with theophylline during their pregnancies.
New Zealand White rabbits received aminophylline (6 mg/kg/12 hr) intravenously from the 26 th to the 30 th day of gestation. Delivery was performed by cesarean section of the day of 30, and the brain of fetuses was sampled.
(1) Body weight and brain wet weight showed no difference between the control group and the experiment group. But brain DNA was decreased and brain protein was slightly increased in the experiment group.
(2) Myelin dry weight, myelin lipid and myelin protein in the experiment group were lower compared with that of the control. Myelin lipid composition in the experiment group showed remarkable changes. Cholesterol of myelin was decreased and phospholipid was not decreased with development. In additon, galactolipid was not increased with development in the experiment group. Phospholipid composition of the myelin in the experiment group was characterized by high percentage of choline phosphoglycerides. Myelin protein composition in the experiment group did not show a significant difference compared with that of the control. 2', 3'-cyclic nucleotide 3'-phosphohydrolase activities of the myelin were lower in the experiment group than that of the control.
Our data indicate that administration of theophylline in the perinatal period results in inhibition of brain cell proliferation and delay of maturation of myelin. This data may be of particular clinical importance in view of the recent increase in the use of theophylline for the prevention of apneic spells in human premature infants.
