الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 161 |  |  |
| | | from | 161 | | |
Abstract
Alzahimer disease is a chronic remitting and disruptive mental disorder associated with significant abnormalities and progressive deterioration of a wide variety of cognitive, psychological, vocational, and behavioral functioning. Because of the complex health problem and wide range of abnormalities and impairments concerning Alzahimer, comperhansive and multimodal treatment approaches should be considered and tested in different combinations, with the goal of reducing patients illness episodes and symptoms, as well as improving their functioning and quality of life in the longer term. The current study was carried out to investigate the following: • The possible beneficial effects of lamotrigene and gabapentin in LPSinduced neurotoxicty (AD-like). • The clarify the molecular mechanisms by which they exert their beneficial effects. In order to achieve these goals, neuro-inflammation and amyloidogenesis, in a simulation to AD, were induced by LPS (a single I.P. injection of 0.8 mg/kg) was used for inducing brain. Animals were randomly divided into five groups (16 mice in each group): • Normal control group • LPS group Mice were injected with LPS (single dose of 0.8 mg/kg, I.P.). • Lamotrigine group Mice were injected by LPS and then received lamotrigene (30mg/kg/day, P.O.) starting two hours after LPS injection and continued for seven successive days. • Gabapentin group Mice were injected by LPS and then received gabapentin (200mg/kg/day, P.O) starting two hours after LPS injection and continued for seven successive days. • Lamotrigine + Gabapentin group Mice were injected by LPS and received both oral lamotrigene (30 mg/kg) and gabapentin (200 mg/kg) starting two hours after LPS injection for seven consecutive days. Twenty- four hours following the end of the treatment regimen. Animals were classified into two groups, the first group was used to assess the following behavioral tests: • Y-maze test • Novel object recognition test. - The second group of animals were anesthetized and killed by cervical dislocation and brain samples were collected and divided into two parts. One part was kept frozen at -80οC to evaluate the following biochemical parameters: • Acetylcholine esterase (AchE) enzyme content. • Glutamate content. • Glutathione (GSH) content. • Malondialdhyde (MDA) content. • Superoxide dismutase (SOD) enzyme content. - The second part of brain samples was fixed in 10% neutral buffered formalin (pH 7.4) for 72 h, washed, dehydrated, embedded in paraffin wax and sectioned serially with a microtome at 3 μm thickness. They were all stained with hematoxylin and eosin (H&E) for histopathological examination. The effects of LPS (0.8 mg/kg, I.P.) on assessed parameters compared to the normal control group can be summarized as follows: • Significant decrease in SAP (%). • Significant decrease in recognition index. • Significant increase in AchE content. • Significant increase in Glutamate content. • Significant increase in brain tissue MDA content. • Significant decrease in brain tissue GSH content. • Significant decrease in brain tissue SOD content. • Histopathological examination of brain section showed decreased neuronal cell population with ischemic neuronal injury and focal gliosis and perivascular edema. The effects of Lamotrigene (30mg/kg, P.O.) on assessed parameters compared to LPS group can be summarized as follows: • Significant increase in recognition index. • Significant increase in SAP (%). • Significant increase in SOD content. • Significant increase in GSH content. • Significant decrease in MDA content. • Significant decrearse in AchE content. • Significant decrease in glutamate content. • Histopathological examination of brain sections showed slight degree of ischemic neuronal injury. The effects of Gabapentin (200mg/kg, P.O.) on assessed parameters compared to LPS group can be summarized as follows: • Significant increase in recognition index. • Significant increase in SAP (%). • Significant increase in SOD content. • Significant increase in GSH content. • Significant decrease in MDA content. • Significant decrease in AchE content. • Significant decrease in glutamate content. • Hostopathological examination of brain sections demonstrated mild degree of both ischemic neuronal injury and perivascular edema. The effects of Lamotrigene and Gabapentin combination on assessed parameters compared to LPS group can be summarized as follows: • Significant increase in recognition index. • Significant increase in SAP (%). • Significant increase in SOD content. • Significant increase in GSH content. • Significant decrease in MDA content. • Significant decrease in AchE content. • Significant decrease in glutamate content. • Histopathological examination of brain sections showed slight degree of ischemic neuronal injury.