ABSTRACT
MECHANISMS OF PERSISTENT TRANSLATION ARREST FOLLOWING GLOBAL BRAIN ISCHEMIA and REPERFUSION
by
JILL T. JAMISON
December 2011
Advisor: Donald J. DeGracia, Ph.D.
Major: Physiology
Degree: Doctor of Philosophy
The information presented here studies the mechanisms that underlie persistent translation arrest (TA) following global brain ischemia and reperfusion (I/R). To summarize the main findings I have discovered a new mechanism for prolonged post-ischemic TA that correlated exactly with in vivo translation rates and correlated precisely with cell outcome. Through the extensive colocalization studies, my results indicate that the mRNA granules are ribonomic structures involved with mRNA regulation. This finding is significant because it shifts the focus onto mRNA metabolism and away from ribosomal molecular biology. I have identified new pathways to investigate for understanding why there is selective delayed death in post-ischemic neurons, however my work also gives insight into why resistant neurons survive. The results were tested in a whole animal (male Long Evans rats) model of global brain I/R using in situ antibodies and mRNA staining methods, in viv0 protein synthesis and Western blots. Results are collectively summarized below:
1. Cytoplasmic poly(A) containing mRNAs redistributed to form mRNA granules in reperfused neurons.
2. mRNA granules sequester mRNA away from both the small and large ribosomal subunits, providing a novel mechanism of prolonged TA in post-ischemic neurons.
3. mRNA granules are ribonomic structures.
4. mRNA granules, are neither stress granules, processing bodies, or polysomes.
5. mRNA granules were found to only colocalize with eIF4G, PABP and HuR, suggesting that mRNA granules may itself be related to or a subset of the ELAV/Hu granule.
6. HuR co-localized to mRNA granules and translation of HSP-70. This correlation suggests mRNA granules are involved in post-transcriptional stress gene regulation in reperfused neurons.
7. mRNA granules are causally linked to TA.
","abstract_html":"<p>ABSTRACT</p> <p>MECHANISMS OF PERSISTENT TRANSLATION ARREST FOLLOWING GLOBAL BRAIN ISCHEMIA and REPERFUSION</p> <p>by</p> <p>JILL T. JAMISON</p> <p>December 2011</p> <p>Advisor: Donald J. DeGracia, Ph.D.</p> <p>Major: Physiology</p> <p>Degree: Doctor of Philosophy</p> <p>The information presented here studies the mechanisms that underlie persistent translation arrest (TA) following global brain ischemia and reperfusion (I/R). To summarize the main findings I have discovered a new mechanism for prolonged post-ischemic TA that correlated exactly with <i>in vivo</i> translation rates and correlated precisely with cell outcome. Through the extensive colocalization studies, my results indicate that the mRNA granules are ribonomic structures involved with mRNA regulation. This finding is significant because it shifts the focus onto mRNA metabolism and away from ribosomal molecular biology. I have identified new pathways to investigate for understanding why there is selective delayed death in post-ischemic neurons, however my work also gives insight into why resistant neurons survive. The results were tested in a whole animal (male Long Evans rats) model of global brain I/R using <i>in situ</i> antibodies and mRNA staining methods, <i>in viv0</i> protein synthesis and Western blots. Results are collectively summarized below:</p> <p>1. Cytoplasmic poly(A) containing mRNAs redistributed to form mRNA granules in reperfused neurons.</p> <p>2. mRNA granules sequester mRNA away from both the small and large ribosomal subunits, providing a novel mechanism of prolonged TA in post-ischemic neurons.</p> <p>3. mRNA granules are ribonomic structures.</p> <p>4. mRNA granules, are neither stress granules, processing bodies, or polysomes.</p> <p>5. mRNA granules were found to only colocalize with eIF4G, PABP and HuR, suggesting that mRNA granules may itself be related to or a subset of the ELAV/Hu granule.</p> <p>6. HuR co-localized to mRNA granules and translation of HSP-70. This correlation suggests mRNA granules are involved in post-transcriptional stress gene regulation in reperfused neurons.</p> <p>7. mRNA granules are causally linked to TA.</p>","abstract_has_math":false,"creators":["Jamison, Jill Theresa"],"institution":null,"degree_name":"Ph.D.","degree_level":"Open Access Dissertation","degree_discipline":"Physiology","degree_department":null,"school":null,"contributors":["Donald J. DeGracia"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-01-01T08:00:00Z","date_published":"2011-01-01T08:00:00Z","updated_at":"2026-07-24T05:59:04Z","subjects":["Delayed Neuronal Death, Ischemia and Reperfusion, mRNA granules, Ribonomics, Stress Response, Translation Arrest","Neurosciences","Physiology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.wayne.edu/oa_dissertations/414","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Donald J. DeGracia"]},{"key":"dc:creator","label":"Author","values":["Jamison, Jill Theresa"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2011-01-01T08:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Physiology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Open Access Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Delayed Neuronal Death, Ischemia and Reperfusion, mRNA granules, Ribonomics, Stress Response, Translation Arrest","Neurosciences","Physiology"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.wayne.edu/oa_dissertations/414"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["ABSTRACT
MECHANISMS OF PERSISTENT TRANSLATION ARREST FOLLOWING GLOBAL BRAIN ISCHEMIA and REPERFUSION
by
JILL T. JAMISON
December 2011
Advisor: Donald J. DeGracia, Ph.D.
Major: Physiology
Degree: Doctor of Philosophy
The information presented here studies the mechanisms that underlie persistent translation arrest (TA) following global brain ischemia and reperfusion (I/R). To summarize the main findings I have discovered a new mechanism for prolonged post-ischemic TA that correlated exactly with in vivo translation rates and correlated precisely with cell outcome. Through the extensive colocalization studies, my results indicate that the mRNA granules are ribonomic structures involved with mRNA regulation. This finding is significant because it shifts the focus onto mRNA metabolism and away from ribosomal molecular biology. I have identified new pathways to investigate for understanding why there is selective delayed death in post-ischemic neurons, however my work also gives insight into why resistant neurons survive. The results were tested in a whole animal (male Long Evans rats) model of global brain I/R using in situ antibodies and mRNA staining methods, in viv0 protein synthesis and Western blots. Results are collectively summarized below:
1. Cytoplasmic poly(A) containing mRNAs redistributed to form mRNA granules in reperfused neurons.
2. mRNA granules sequester mRNA away from both the small and large ribosomal subunits, providing a novel mechanism of prolonged TA in post-ischemic neurons.
3. mRNA granules are ribonomic structures.
4. mRNA granules, are neither stress granules, processing bodies, or polysomes.
5. mRNA granules were found to only colocalize with eIF4G, PABP and HuR, suggesting that mRNA granules may itself be related to or a subset of the ELAV/Hu granule.
6. HuR co-localized to mRNA granules and translation of HSP-70. This correlation suggests mRNA granules are involved in post-transcriptional stress gene regulation in reperfused neurons.
7. mRNA granules are causally linked to TA.
"]},{"key":"dc:title","label":"Title","values":["Mechanisms of persistent translation arrest following global brain ischemia and reperfusion"]}]}],"canonical_facts":{"dc:contributor":["Donald J. DeGracia"],"dc:creator":["Jamison, Jill Theresa"],"dc:date.available":["2011-01-01T08:00:00Z"],"dc:description.abstract":["ABSTRACT
MECHANISMS OF PERSISTENT TRANSLATION ARREST FOLLOWING GLOBAL BRAIN ISCHEMIA and REPERFUSION
by
JILL T. JAMISON
December 2011
Advisor: Donald J. DeGracia, Ph.D.
Major: Physiology
Degree: Doctor of Philosophy
The information presented here studies the mechanisms that underlie persistent translation arrest (TA) following global brain ischemia and reperfusion (I/R). To summarize the main findings I have discovered a new mechanism for prolonged post-ischemic TA that correlated exactly with in vivo translation rates and correlated precisely with cell outcome. Through the extensive colocalization studies, my results indicate that the mRNA granules are ribonomic structures involved with mRNA regulation. This finding is significant because it shifts the focus onto mRNA metabolism and away from ribosomal molecular biology. I have identified new pathways to investigate for understanding why there is selective delayed death in post-ischemic neurons, however my work also gives insight into why resistant neurons survive. The results were tested in a whole animal (male Long Evans rats) model of global brain I/R using in situ antibodies and mRNA staining methods, in viv0 protein synthesis and Western blots. Results are collectively summarized below:
1. Cytoplasmic poly(A) containing mRNAs redistributed to form mRNA granules in reperfused neurons.
2. mRNA granules sequester mRNA away from both the small and large ribosomal subunits, providing a novel mechanism of prolonged TA in post-ischemic neurons.
3. mRNA granules are ribonomic structures.
4. mRNA granules, are neither stress granules, processing bodies, or polysomes.
5. mRNA granules were found to only colocalize with eIF4G, PABP and HuR, suggesting that mRNA granules may itself be related to or a subset of the ELAV/Hu granule.
6. HuR co-localized to mRNA granules and translation of HSP-70. This correlation suggests mRNA granules are involved in post-transcriptional stress gene regulation in reperfused neurons.
7. mRNA granules are causally linked to TA.
"],"dc:identifier":["https://digitalcommons.wayne.edu/oa_dissertations/414"],"dc:subject":["Delayed Neuronal Death, Ischemia and Reperfusion, mRNA granules, Ribonomics, Stress Response, Translation Arrest","Neurosciences","Physiology"],"dc:title":["Mechanisms of persistent translation arrest following global brain ischemia and reperfusion"],"thesis:degree_discipline":["Physiology"],"thesis:degree_level":["Open Access Dissertation"],"thesis:degree_name":["Ph.D."]},"updated_at":"2026-07-24T05:59:04Z"}