Neuroprotective effects of melatonin upon the offspring cerebellar cortex in the rat model of BCNU-induced cortical dysplasia

• Published in: Brain research 2007-07, Vol.1160, p.134-144
• Main Authors: Uyanıkgil, Yiğit, Baka, Meral, Ateş, Utku, Turgut, Mehmet, Yavaşoğlu, Altuğ, Ülker, Sibel, Sözmen, Eser Yıldırım, Sezer, Ebru, Elmas, Çiğdem, Yurtseven, Mine Ertem
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Biological and medical sciences; Brain Diseases - etiology; Brain Diseases - pathology; Brain Diseases - prevention & control; Bromodeoxyuridine - metabolism; Carmustine; Cerebellar Cortex - drug effects; Cerebellar Cortex - pathology; Cerebellar Cortex - ultrastructure; Cerebellum; Cortical dysplasia; Disease Models, Animal; Female; In Situ Nick-End Labeling - methods; Malondialdehyde - metabolism; Medical sciences; Melatonin; Melatonin - therapeutic use; Microscopy, Electron, Transmission - methods; Nerve Tissue Proteins - metabolism; Neurology; Neuropharmacology; Neuroprotective agent; Neuroprotective Agents - therapeutic use; Offspring; Pharmacology. Drug treatments; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Prenatal Exposure Delayed Effects - pathology; Prenatal Exposure Delayed Effects - physiopathology; Rat; Rats; Rats, Wistar; Superoxide Dismutase - metabolism; Transforming Growth Factor beta1 - metabolism
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2007.05.025

Abstract Cortical dysplasia is a malformation characterized by defects in proliferation, migration and maturation. This study was designed to evaluate the alterations in offspring rat cerebellum induced by maternal exposure to carmustine-[1,3-bis (2-chloroethyl)-1-nitrosoure] (BCNU) and to investigate the effects of exogenous melatonin upon cerebellar BCNU-induced cortical dysplasia, using histological and biochemical analyses. Pregnant Wistar rats were assigned to five groups: intact-control, saline-control, melatonin-treated, BCNU-exposed and BCNU-exposed plus melatonin. Rats were exposed to BCNU on embryonic day 15 and melatonin was given until delivery. Immuno/histochemistry and electron microscopy were carried out on the offspring cerebellum, and levels of malondialdehyde and superoxide dismutase were determined. Histopathologically, typical findings were observed in the cerebella from the control groups, but the findings consistent with early embryonic development were noted in BCNU-exposed cortical dysplasia group. There was a marked increase in the number of TUNEL positive cells and nestin positive cells in BCNU-exposed group, but a decreased immunoreactivity to glial fibrillary acidic protein, synaptophysin and transforming growth factor β1 was observed, indicating a delayed maturation, and melatonin significantly reversed these changes. Malondialdehyde level in BCNU-exposed group was higher than those in control groups and melatonin decreased malondialdehyde levels in BCNU group ( P < 0.01), while there were no significant differences in the superoxide dismutase levels between these groups. These data suggest that exposure of animals to BCNU during pregnancy leads to delayed maturation of offspring cerebellum and melatonin protects the cerebellum against the effects of BCNU.