Expression of matrix metalloproteinases in cerebrovascular endothelial cells /
Multiple Sclerosis (MS) is a debilitating disease that causes inflammation and demyelination of the central nervous system (CNS). A sclerosis forms at the site of myelin damage and can eventually block the propagation of action potentials down nerve fibers. A compromised blood brain barrier (BBB), o...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
2004.
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| Summary: | Multiple Sclerosis (MS) is a debilitating disease that causes inflammation and demyelination of the central nervous system (CNS). A sclerosis forms at the site of myelin damage and can eventually block the propagation of action potentials down nerve fibers. A compromised blood brain barrier (BBB), one of the first signs of relapse, allows lymphocytes to cross into brain tissue, where they subsequently release chemotactic factors triggering inflammation and demyelination within the CNS. Matrix metalloproteinases (MMPs) are important in initiating the neuroinflammatory response caused by the lymphocytes that infiltrate into the CNS through the BBB; of the MMPs identified, MMP-2 and MMP-9 have been implicated in the dissolution of the barrier. While the pathology of MS remains unclear, it is believed that an infectious agent is a potential initiating factor (Acheson, 1977). In this manner, Theiler's murine encephalomyelitis virus (TMEV) in mice poses as an excellent model for studying the transmission of an infectious agent within the CNS. TMEV can be classified into two strains: the virulent strain, GDVII, causes fatal encephalitis after intracranial infection, while the persistent strains, BeAn, DA, WW, and Yale, cause a primary demyelinating disease, Theiler's virus induced demyelination (TVID), whose symptoms are similar to those of MS (Lipton, 1975). The following experiment was designed to elucidate the effect of replication of Theiler's virus in cerebrovascular endothelial (CVE) cells from TVID-susceptible (SJL/J) versus TVID-resistant (BALB/c) strains of mice. Both strains of CVE cells were infected/ treated with one of the following: BeAn, GDVII, positive controls TNF-α, IL-1β and IFN-γ, and a serum-free negative control. The cell supernatants were tested for the presence of MMP-2 and MMP-9 by use of zymography. The CVE cells from both strains of mice, BALB/c and SJS/L, were found to express MMP-2 and MMP-9 when treated with cytokines TNF-α and IL-1β, while viral infection did not induce expression. This expression disrupts the protective specificity of the barrier, allowing lymphocytes to cross over and subsequently cause neuroinflammation. Understanding the early pathological events that occur at the BBB may allow for the future development of therapeutic interventions in treatments of MS. |
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| Item Description: | Vita. "Major Subject: Biomedical Science". |
| Physical Description: | vi, 30 leaves : illustrations ; 28 cm. |
| Bibliography: | Includes bibliographical references (leaves 28-29). |