The role of brain derived neurotrophic factor in multiple sclerosis and the role of fractalkine in multiple sclerosis induced neuropathic pain
| dc.contributor.author | Zhu, Wenjun | |
| dc.contributor.examiningcommittee | Gong, Yuewen (Pharmacy) Gu, Xiaochen (Pharmacy) Vrontakis-Lautatzis, Maria (Human Anatomy and Cell Science) Xiao, Lan (Third Military Medical University) | en_US |
| dc.contributor.supervisor | Namaka, Mike (Pharmacy) | en_US |
| dc.date.accessioned | 2013-02-15T15:00:52Z | |
| dc.date.available | 2013-02-15T15:00:52Z | |
| dc.date.issued | 2010-03 | en_US |
| dc.date.issued | 2011-09 | en_US |
| dc.date.issued | 2010-09 | en_US |
| dc.degree.discipline | Pharmacy | en_US |
| dc.degree.level | Doctor of Philosophy (Ph.D.) | en_US |
| dc.description.abstract | Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease, characterised by demyelination in the central nervous system (CNS). The exact pathophysiology of MS is still unknown but it is believed to be associated with infiltration of T cells and activation of microglia that result in myelin damage leading to neurological deficits including neuropathic pain. Current treatment strategies such as glatiramer acetate have recognized the importance of BDNF in myelin repair. In addition, the proposed role of the chemokine CX3CL1 and its receptor CX3CR1 in the control of microglia activation and leukocyte infiltration place this chemokine in an important position in regulation of MS-induced neuropathic pain. In this research study, the experimental autoimmune encephalomyelitis (EAE) rat model of MS was used to examine the role of BDNF in myelin repair as well as CX3CL1’s role in neuropathic pain. Methods: A total of 66 adult female Lewis rats are divided into 3 experimental groups: naïve control, active control and active EAE. Naïve control animals do not receive any injections. Active control animals receive 2 intraperitoneal injections of pertussis toxin and injections of Freund’s adjuvant and Mycobacterium Tuberculosis. Active EAE animals receive the same regimen administered to active controls plus full inoculation with fatty acid and Guinea pig myelin basic protein. Expressions of BDNF, CX3CL1 and CX3CR1 in a time dependent mansion (day 0, 3, 6, 9, 12 &15) were examined using immunohistochemistry (IHC), ELISA, Western blot, RT-PCR and real time-PCR. Results: There was a significant increase in BDNF, CX3XL1 and CX3CR1 expression of protein and mRNA in DRG at day 12 after induction of MS. The neurons and glial cells were identified to express BNDF, CX3XL1 and CX3CR1 in the spinal cord of EAE animal. Conclusion: The antigenic-induced expression of BDNF within the DRG may represent a key element involved in facilitating central myelin repair. In addition, the chemokine CX3CL1 and its receptor CX3CR1 represent key mediators involved in the development of MS-induced pain. Keywords: Multiple sclerosis, MS, experimental autoimmune encephalomyelitis, EAE, CX3CL1, CX3CR1, neuropathic pain, myelin repair | en_US |
| dc.description.note | May 2013 | en_US |
| dc.identifier.citation | Pharmacy Practice | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/16675 | |
| dc.language.iso | eng | en_US |
| dc.publisher | Journal of Neuroscience Methods | en_US |
| dc.publisher | Journal of Cellular and Molecular Medicine | en_US |
| dc.publisher | Pharmacy Practice | en_US |
| dc.rights | open access | en_US |
| dc.subject | BDNF | en_US |
| dc.title | The role of brain derived neurotrophic factor in multiple sclerosis and the role of fractalkine in multiple sclerosis induced neuropathic pain | en_US |
| dc.type | doctoral thesis | en_US |