Contrast neonates

The most significant of the abnormalities observed in a hypothyroid brain is a hypoplastic neuropile, i.e., a marked reduction in the number of connections between neurons [102], This has been observed both in the cerebrum and the cerebellum. For instance a permanent and dramatic reduction in the arborization of the dendritic tree of the Purkinje cell is observed in the hypothyroid cerebellum [103]. The length of the primary dendritic trunk is increased and a deficit in the number, density and branching of the dendritic spines is noticed. In contrast neonatal hyperthyroidism accelerates development of spines. Similar findings have been reported for the cerebrum, i.e., reduction in length and branching of pyramidal neurons, of the density of axonal terminals and of the number of spines [102],... 

The main rout of excretion of the drug and its metabolites is the kidney with a half-life of 9-18 h in human. In contrast to human, animal models have a lower elimination half-life ranging from 0.6-9 h [78]. The elimination half-life of valproic acid and some metabolites was found to be much longer in the neonates (40-50 h) than adult subjects (9-18 h) [78,81]. One study reported no difference between the elimination half-life between elderly and young subjects (15.4 and 13.0 h, respectively) while other found an increase in for older patients (14.9 versus 7.2 h for young patients) [78,90], Insignificant amounts of valproic acid are found in breast milk, approximately 3% of maternal drug levels [84]. 

Developmentally, thyroid hormones interact with sex hormones such that hypothyroidism prolongs the critical period for testosterone-induced defeminization (see below) [3] in contrast, the hyperthyroid state prematurely terminates the sensitivity to testosterone [3]. Undoubtedly, an important link in these and other effects is synapse formation. Hypothyroidism increases synaptic density, at least transiently [3]. Interesting parallels with synapse formation are reported for learning behavior in rats neonatal hypothyroidism impairs learning ability, whereas hyperthyroidism accelerates learning initially, followed by a decline later in life [3]. 

Graves disease may occur in the newborn infant, either due to passage of maternal TSH-R Ab [stim] through the placenta, stimulating the thyroid gland of the neonate, or to genetic transmission of the trait to the fetus. Laboratory studies reveal an elevated free T4, a markedly elevated T, and a low TSH—in contrast to the normal infant, in whom TSH is elevated at birth. 

The initial steps in BA synthesis are characterised by the introduction of a hy-droxylic group in the la position, or in position 27, followed by another in the la position into the cholesterol nucleus. Both synthetic pathways (the neutral and the acidic pathways) possess a distinct microsomal 7-oxysterol hydroxylase, which is regulated by different genes. The most recently described disorder of BA synthesis is cholesterol 7a-hydroxylase deficiency, in which their decreased production through the classical pathway is partially balanced by activation of the alternative pathway. Cholesterol levels increase in the liver, with a consequent low-density lipoprotein hypercholesterolemia, and cholesterol gallstones may result, although there is no liver disease. In contrast, a defect in the conversion of 27-hydroxy-cholesterol to la,27-dihydroxy-cholesterol due to deficiency of the oxysterol 7a-hydroxylase specific for the alternate pathway, causes severe neonatal liver disease [8]. 

Dembinski J, Arpe V, Kroll M, Hieronimi G, Bartmann P. Thyroid function in very low birthweight infants after intravenous administration of the iodinated contrast medium iopromide. Arch Dis Child Fetal Neonatal Ed 2000 82(3) F215-7. 

In primary cultures of neonatal cerebellar granule neurons, all Ca2+ sensors, calmodulin, protein kinases C (PKC), and the p21(ras)/phosphatidylinositol 3 -kinase (Ptdlns-3K)/Akt pathway, converge towards NF-kB at the levels of nuclear translocation as well as transcription. The duration of NF-kB activation is a critical determinant for sensitivity toward excitotoxic stress and is dependent on the different upstream and downstream signaling associated with various kinases. This is in contrast to studies in non-neuronal cells, which either do not respond to Ca2+ or do not simultaneously activate all three cascades (Lilienbaum and Israel, 2003). Collective evidence suggests that brain inflammatory processes differ from systemic inflammation not only in the involvement of various types of neural cells but also in differences in response to second messengers. 

Drug administration is a common method to study neonatal RSD. Both subcutaneous injection and oral administration are applicable. The consequence of neonatal RSD by drug depends on the dose and the way that the drug was administered, such as the treatment duration (38,49). In contrast to an adult response, RSD in the rat at age 2 weeks or younger does not produce a REM rebound to REM suppression (50). Therefore, a dose-response relationship between drug and REM suppression is not as easy to differentiate as in adult models. For uniformity, an injection of a full dose once a day may not produce the same result as an injection of this dose split into a twice-daily dose (51). One to two weeks of total treatment duration with appropriate doses has been proven to be effective in producing long-term developmental abnormalities (38). 

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