The development of an in vitro model of strain induced cell injury and its application in the investigation of neurodegeneration /
There are a number of injuries and diseases that are characterized by elevation of pressure associated with strain of neurons. An in vitro model of strain induced cell injury was developed to investigate the mechanism of neurodegeneration. A low level of strain was administered to neuronal cells via...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
2000.
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| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=731990441&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | There are a number of injuries and diseases that are characterized by elevation of pressure associated with strain of neurons. An in vitro model of strain induced cell injury was developed to investigate the mechanism of neurodegeneration. A low level of strain was administered to neuronal cells via fluid shear stress and substrate stretch. Application of 8% strain via fluid shear stress led to phosphasidylserine accumulation on the external membrane surface, DNA fragmentation, and loss of cellular redox potential. Lactate dehydrogenate (LDH) release by injured cells did not differ significantly from LDH release from untreated cells, indicating that cells deformed via fluid shear stress maintained the integrity of their plasma membranes. Nitric oxide production by sheared cells increased over that of unshelled control cells. Inhibition of nitric oxide production attenuated injury. These results demonstrated that application of shear stress led to injury consistent with apotosis. Furthermore, application of 14% strain via substrate stretch also led to DNA fragmentation, however, it was accompanied by LDH release and a delayed increase in nitric oxide production. After confirming that strain leads to DNA fragmentation, investigations were conducted to elucidate the mechanism of this cell injury. Using pharmacological agents, the role of calcium and G proteins, two important cellular signaling molecules, in mediating apoptosis was elucidated. Strain injury led to a disruption of calcium homeostasis by entry of calcium through NMDA gated channels and releases from internal stores. G proteins and calcium were shown to modulate the level of nitric oxide production. Inhibition of G protein activation and calcium entry and release from stores was neuroprotective. Events occurring further downstream in strain induced apostolic pathway included new protein synthesis and the increased in activity of canvases, a group of proteins well known to carry out the final step in the death cascade. These results may lead to novel therapies in treatment of head injury aimed at prevention of apoptosis. |
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| Item Description: | Vita. "Major Subject: Chemical Engineering". |
| Physical Description: | xiii, 215 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilm Inc. |
| Bibliography: | Includes bibliographical references (leaves 179-213). |