الفهرس 
Introduction and aim of the workOnly 14 pages are availabe for public view
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Abstract
Pregabalin (PGB) is an oral anticonvulsant drug and has a chemical structural similar to the gabapentin, pregabalin is novel gamma aminobutyric acid (GABA) analog which is not bound to GABA receptors but acts by inhibiting certain calcium channels, Pregabalin mechanism of action is inhibiting calcium influx and subsequent release of excitatory neurotransmitters, this is the cause of its neurotoxic effects as ion channels and neurotransmitter system in the brain are responsible for regulation of processes essential for the development of the brain. Very few information have been presented about teratogenic potentials of pregabalin.
This work aimed to study the effect of different doses of pregabalin on pre and postnatal development of the cerebellar cortex in albino rats by using light and transmission electron microscope.
The animals were subdivided into three groups:
The groups were:
group A: Includes 25 offsprings of 20 control mothers received distilled water.
group B: Includes 25 offsprings of 20 mothers treated with pregabalin at dose of 150mg/kg.
group c: includes 25 offsprings of 20 mothers treated with pregabalin at dose of 600mg/kg.
In the three groups the numbers were taken prenatally (age 18 day) after determination of the date of pregnancy by using vaginal smear and the remaining were taken postnatal (age 1, 2, 3 weeks) in addition to adult age (2.5 months).
Pregabalin was administered to pregnant rat (at a dose of 150 mg/kg and a dose of 600 mg/kg by oral tube daily) starting from the 1st day of the positive vaginal smear till birth and during whole period of lactation (up to postnatal day 21).
Then the rats were sacrificed by decapitation then the skulls were opened and the brains were extracted. The cerebellum was removed immediately and processed for light and transmission electron microscope.
Thereby, the following findings were observed:
• The external granular layer increases in thickness in pregabalin treated groups than that of the age-matched controls, this increase is more manifested during the 2nd and 3rd weeks postnatal may be due to failure of its cells to migrate to their final situation in the molecular and granular layer, and also due to delayed proliferation of cells derived from it.
• The molecular layer of treated group is less in thickness in all treated groups than that of the age-matched controls, this decrease in thickness of the molecular layer may be due to decrease in cellular processes that grow through this layer specially those of purkinje and granule cells, also may be due to a decrease in the number of migrating cells from the external granular layer to it.
• The Purkinje cell layer in treated group, the purkinje cells appeared shrunken with loss of their piriform shape; the cytoplasm had destructed organelles up to completely degenerated cells this may be due to extrinsic insults to the cells such as osmotic or toxic traumatic effect of the pregabalin.
• The internal granular layer in treated group is delayed in its differentiation from the white matter. This layer is thinner than that of the control group which is manifested mainly postnatal. This decrease in thickness of the internal granular layer may be due to failure of cells to migrate to this layer from the external granular layer and may be due to direct degenerative effect of pregabalin on these cells.
• The ultrastructural study of Purkinje cells and granule cells show some degenerative changes in the form of small size of the cells and of the nucleus which appear destructed, this may be due to change in the nuclear envelope structure by decreasing its permeability.
• The cytoplasm of the treated cells showed degenerated mitochondria with destructed cristae, this may be due to pregabalin-induced oxidative impairment of tissues and elevated apoptosis–inducing factor levels in mitochondria.
• The rough endoplasmic reticulum of the treated cells appeared dilated due to accumulation of unfolded or misfolded proteins in their lumen which finely leads to cell death.
Conclusion
• Pregabalin administration during pregnancy and lactation causes its marked effect during early postnatal life and this effect extend till the adult stage of the offsprings.
• The effect of pregabalin on the cerebellum becomes evident during postnatal life than prenatal age.
• Pre and postnatal administration of pregabalin in both low and high doses proved loss of cellular components, distortions of cerebellar cortical cells in a dose dependent manner.
Recommendations
• Pregabalin exposure (at a low dose of 150 mg\kg and a high dose of 600 mg\kg) is neurotoxic and must be avoided by pregnant and lactating mother.
• Further researches are needed to define the most critical period of pregabalin toxicity. Alternatives of more safe antiepileptic drugs during pregnancy and lactation should be available.