Evaluation of histological and ultrastructural changes provoked by prenatal tramadol

Tramadol is a novel centrally acting analgesic. Despite, its implementation during pregnancy may impair neuronal survival and synaptic development in neonatal cerebella. The current investigation assessed the histological and ultrastructural alterations in postnatal cortical cerebellar neuronal development induced by prenatal tramadol. ۳۰ offsprings were divided to control group I: fifteen pups born to mothers given saline from D۱۰ till D۲۱ of gestation. Tramadol-treated group II: fifteen pups born to mothers received tramadol HCL (۵۰ mg/kg/day) from D۱۰ till D۲۱ of gestation. Pups were categorized into three subgroups (a, b, and c) and offered for sacrifice on the ۱ seventh, fourteenth and twenty-first post-natal days. Light microscopic examination revealed the overcrowding and signs of red degeneration affecting purkinje cell layer. Neurodegenerative signs of both purkinje and granule cell neurons were also confirmed by TEM in form of chromatin condensation, dilated Golgi channels, disrupted endoplasmic reticulum, marked infolding of the nuclear envelope and decrease in granule cell precursors. In addition, the astrocytic processes and terminal nerve axons appeared with different degrees of demyelination and decreased number of oligodendrocytes and degenerated mitochondria. Furthermore, group II exhibited an increase in P۵۳ immune expression. The area percentage of apoptotic cells detected by TUNEL assay was significantly increased. Besides to the significant decrease of Ki۶۷ immunoreactivity in the stem neuronal cell progenitors. Quantitative PCR results showed a significant decline in micro RNA۷ gene expression in tramadol treated groups resulting in affection of multiple target genes in P۵۳ signaling pathways, improper cortical size and defect in neuronal development