Neuroinflammation and excitotoxicity are frequently regarded as the classical hallmarks of all major central nervous system (CNS) diseases such as stroke and neurodegenerative disorders. However, the limited number of current clinical options for the treatment of these diseases and the side effects associated with these treatment options indicate that there is an urgent and important need to develop drugs that delay neurological diseases. Although the molecular mechanisms underlying these neurological diseases remain poorly understood, it is widely accepted that alterations in microglia function is the key causative factor. It was recently reported that granulocyte colony-stimulating factor (G-CSF) and a natural marine compound, GB9, show great potential as anti-inflammatory agents. In the present study, we used a model of neuroinflammation to investigate the neuroprotective effects of G-CSF and GB9, and whether they exert an anti-neuroinflammatory effect on IFN-£^-stimulated microglia (BV2). Our results revealed that both G-CSF and GB9 attenuate the upregulation of proinflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in IFN-£^-stimulated microglia. Furthermore, Western blot and immunohistochemical analyses revealed that G-CSF or GB9 prevent downregulation of the glutamate transporter (Glu-Asp transporter, GLAST) and activation of the glutamate receptor in the IFN-£^-stimulated microglia. Additionally, our in vivo analyses revealed that centrally administered G-CSF could reverse the increase of OX-42 immunoactivity, which is the marker of IFN-£^-stimulated microglia. In summary, our findings support the hypotheses that G-CSF and the marine compound, GB9, possess anti-neuroinflammatory properties and could be pursued as potential therapeutic agents for CNS diseases.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0909110-115923 |
| Date | 09 September 2010 |
| Creators | Shen, Jau-wen |
| Contributors | Kang Lu, Wu-fu Chen, Zhi-hong Wen, Chung-lung Cho |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | Cholon |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0909110-115923 |
| Rights | not_available, Copyright information available at source archive |
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