الفهرس Only 14 pages are availabe for public view
 |  | from | 155 |  |  |
| | | from | 155 | | |
Abstract
PD is a late onset, progressive, neurodegenerative, and movement disorder. Neuroinflammation mediated by microglia activation and the generation of pro-inflammatory and neurotoxic factors appear to play an essential role in the pathogenesis of PD. Current drug therapies for PD are symptomatic and appear to bear little effect on the progressive neurodegenerative process. Alternatively, inhibition of the inflammatory reaction can attenuate degeneration of nigrostriatal DA pathway. In this context, the present work was designed to investigate the pharmacological modulation of the neuroinflammatory process by anti-inflammatory or microglia inhibitory drugs as a possible neuroprotective strategy for treating PD.
Methods
One hundred and seventy six male albino rats were used in the current study. Animals were divided into 10 groups. Rotenone was dissolved in dimethylsulfoxide and the rats received 6 injections of sub-chronic doses of rotenone (1.5mg/kg, s.c., every other day). Rats were treated with valproate (50mg/kg, p.o.), nicotinamide (100mg/kg, p.o.), pioglitazone (10mg/kg, p.o.), cerebrolysin (12.5mg/kg, s.c.), celecoxib (20mg/kg, p.o.), meloxicam (5mg/kg, i.p.), pentoxyphillin (30mg/kg, p.o.), or ramipril (10mg/kg, p.o.). All the drugs were administered 1 hr before each rotenone injection.
The rats were screened for motor behavioral impairment using the open field test, rotarod test, and apomorphine-induced rotational behavior one day after the sixth injection of rotenone. After that, animals were deeply anaesthetized and brains were quickly removed. Only one hemisphere from each brain was used for histopathological staining with hematoxylin and eosin for sections cut through the substantia nigra. The second hemisphere of each brain was kept at –80˚C.
Results
Results showed that rotenone treated rats exhibited decreased mobility and motor in-coordination accompanied by marked lesioning and depigmentation of the substantia nigra neurons and depletion of striatal DA. Further, tumor necrosis factor-α, and superoxide free radical were significantly elevated in the rats striata. This was coupled with increased lipid peroxides and protein carbonyls as well as depletion of intracellular glutathione and reduced catalase activity in the striata. Treatment with celecoxib, valproate, pentoxyphillin, or nicotinamide protected against the toxic effect of rotenone. On the other hand, ramipril and pioglitazone afforded mild protection, whereas, meloxicam and cerebrolysin did not provide protection against the neurotoxicity of rotenone.
Conclusion
Our study reinforces the view that anti-inflammatory and microglia inhibitory drugs, may have utility in treating PD patients once clinical disabilities appear to prevent the rapid progression of the disease.