Experimental models of congenital hydrocephalus and comparable clinical problems in the fetal and neonatal periods

Morphological and developmental changes of the ventricular system are analyzed in three major experimental models of congenital hydrocephalus in the rat: 6-aminonicotinamide (6-AN)-induced and LEW/Jms and HTX mutant hydrocephalus. The clinically comparable forms of hydrocephalus and problems occurring during each period of intrauterine hydrocephalus are then discussed. Comparative morphological study revealed that 6-AN-induced hydrocephalus was comparable to the Dandy-Walker syndrome and that the critical period regarding this syndrome in fetal life was at the time of "legal termination". The LEW/Jms and HTX mutant models were identical with regard to the form of progressive hydrocephalus in the postnatal period, but the condition underlying the hydrocephalus during the fetal period differed. The LEW/Jms model was comparable to primary congenital aqueductal stenosis (aqueductal agenesis), and the hydrocephalic state appeared in the period of "intrauterine preservation" before pulmonary maturation was completed. On the other hand, the HTX fetuses demonstrated secondary change of the aqueduct in the perinatal period, although the model was considered to be of congenital communicating hydrocephalus. Cerebrospinal fluid (CSF) dynamics studied in the fetuses with 6-AN-induced hydrocephalus disclosed considerable pathophysiology comparable to "hydromyelic hydrocephalus." The historical trends of animal experimental models of congenital hydrocephalus are reviewed and comparable clinical problems suggested by those models discussed further.