This study aims to understand the mechanism of failure of canalization of cerebral aqueduct following intrauterine exposure to reference teratogen, cyclophosphamide in murine pups. Non-canalization of cerebral aqueduct was found to result in internal hydrocephalus. Cyclophosphamide was administered to pregnant mice on day 10, 11, or 12 of gestation in a single dose of 20 mg/kg body weight. Fetuses were dissected out on day 19 and studied for hydrocephalus and other cerebral or cranial malformations. Serial sections of brain in coronal and transverse planes exhibited incomplete development and failure of canalization of cerebral aqueduct. Pressure of cerebrospinal fluid (CSF) in non-canalized aqueduct resulted in its rupture leading to leakage and accumulation of CSF in brain substance causing a cavity full of CSF close to unopened aqueduct. The large pool of CSF in the brain substance in extreme cases communicated with the subarachnoid space pushing through the substance of brain causing external hydrocephalus. Internal hydrocephalus on the other hand was resulted from back pressure of CSF following blockage in its flow due to non-canalization of the cerebral aqueduct. In the extreme cases internal and external hydrocephalus were seen intercommunicating. Cyclophosphamide induced inhibition of mitosis and cell differentiation of ependymal cells and augmentation of apoptosis of brain cells were attributed as the major causes underlying the incomplete development of cerebral aqueduct. The study also suggested inductive role of CSF in the differentiation of ependymal cells lining the cerebral aqueduct.
|Number of pages||6|
|Publication status||Published - 01-12-2007|
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