Fetal hydrocephalus, intrauterine diagnosis and therapy considerations: an experimental rat model

Fetal hydrocephalus is induced by a single intraperitoneal injection of 8 mg/kg 6-aminonikotinamide (6-AN), a niacinamide antagonist, in Sprague-Dawley rats on day 13 of gestation. Laparotomy was carried out in some rats 3, 6, 7 and 8 days after the intraperitoneal injection. The fetuses were collected by uterotomy and fixed in a formalin solution after measuring head circumference and body length for further histological investigations. The ventricular areas and volumes of the lateral ventricles were measured using a computer morphometric technique after all fetuses were serially sectioned sagittally or coronally. Furthermore, 8 maternal rats (4 treated with 6-AN and 4 controls) were used for ultrasound investigation. The fetal ventricular system and the central canal were demonstrated and compared by transabdominal ultrasound in the 6-AN and control groups. On day 19 of gestation the cerebrospinal fluid (CSF) was drained in some fetuses for 18 h through a thin micro-catheter, which was inserted into the lateral ventricle. In some other fetuses the intracranial pressure (ICP) and the intra-amniotic pressure (IAP) were measured after Doppler sonography of the cerebral blood flow (CBF). These measurements were carried out using a transuterine approach following the laparotomy. Hydrocephalus was produced due to the closure of all outlets of the fourth ventricle. Macrocephalus was clear on day 17 (4 days after 6-AN injection). The entire ventricular system was dilated, including the aqueduct and foramen of Monro, and cerebellar hypoplasia was revealed. Increased ICP in 6-AN fetuses was associated with decreasing CBF. The cerebral mantel was better developed after CSF drainage. The intra-amniotic pressure was increased in all pregnant rats and was either similar to or higher than ICP.