Investigation of maternal melatonin effect on the hippocampal formation of newborn rat model of intrauterine cortical dysplasia

Abstract

Objectives: Cortical dysplasia is a cortical malformation resulting from any developmental defects during different periods of development. This study aims to investigate the hippocampal histopathological alterations in the neonates with cortical dysplasia due to the prenatal exposure to carmustine (1,3-bis (2-chloroethyl)-1-nitrosourea; BCNU) and the possible effects of prophylaxis with melatonin, a neuroprotective agent.

Methods: Wistar albino female rats were randomly divided into four experimental groups; control, melatonin-treated, BCNU-exposed and BCNU-exposed+melatonin-treated. Light microscopy and immunohistochemistry were carried out on the newborn hippocampus.

Results: Histopathology of hippocampus from the control and melatonin-treated groups showed continuity of migration and maturation as pathognomonic signs of the normal newborn hippocampus. Hippocampal cortex from the newborns exposed in utero to BCNU showed the histology of early embryonic hippocampal formation with immunohistochemical increase in the number of nestin positive cells and decreases in the immunoreactivity of glial fibrillary acidic protein (GFAP) and synaptophysin. These findings indicate a significant delay in hippocampal maturation, migration, and synaptogenesis. Intrauterine treatment of BCNU-exposed rats with melatonin resulted in histopathological features almost similar to control group.

Conclusion: It has been concluded that cortical dysplasia induced by intrauterine BCNU administration results in delayed hippocampal maturation, which is successfully restored by intrauterine melatonin treatment.