{"id":{"repo_id":"vt","oai_identifier":"oai:vtechworks.lib.vt.edu:10919/137105"},"canonical_url":"https://search.dev.ndltd.org/etd/vt/oai:vtechworks.lib.vt.edu:10919/137105","repository":{"repo_id":"vt","name":"Virginia Tech","base_url":"https://vtechworks.lib.vt.edu/oai/request"},"display":{"title":"Pericyte and Endothelial Cell Responses within Murine Cerebral Capillaries After Blood Flow Cessation","abstract":"ABSTRACT The microcirculation, encompassing terminal arterioles, capillaries, and venules, plays a pivotal role in the distribution of blood throughout tissues, with capillaries acting as the primary sites for oxygen and nutrient delivery as well as waste product removal. A critical component of the microcirculation is the vascular pericyte (PC), which is essential for angiogenesis and the regulation of microvascular biomechanics. This thesis focuses on the cerebrovascular network, particularly the cerebral microcirculation, and investigates the role of pericytes in maintaining blood-brain barrier (BBB) integrity and neurovascular homeostasis. In this work We highlighted the dynamic interactions between pericytes, endothelial cells, and the extracellular matrix (ECM) in the regulation of microvascular stability and BBB function. underscoring the importance of pericytes in normal physiology and disease. The work investigated the effects of biophysical cues from blood flow on cerebral microcirculation, utilizing an ex vivo murine brain slice model to investigate pericyte behavior under altered hemodynamic conditions. Findings from these experiments suggest that pericytes play an active role in capillary wall remodeling and that changes in hemodynamic forces may lead to vascular dysfunction. Additionally, we optimized a protocol for isolating and characterizing BBB capillaries, along with an analysis of the results that delivers a more precise representation of cerebrovascular structures and their responses across various research contexts. This refined methodology lays the groundwork for future studies on BBB dysfunction in neurological diseases like Alzheimer's and stroke. The thesis also includes an in-depth examination of pericyte morphology and its heterogeneity, and their interactions with the ECM, We believe these approaches offer highly valuable, complementary techniques for characterizing pericytes and gaining insight into their role in the development, maturation, and dysfunction of the microvasculature. The insights gained from this work contribute to a more comprehensive understanding of the molecular and biomechanical mechanisms governing cerebrovascular function. As such, this thesis lays the groundwork for future studies aimed at developing therapeutic interventions targeting pericyte function and BBB integrity, with implications for treating a variety of neurological disorders.","abstract_html":"ABSTRACT The microcirculation, encompassing terminal arterioles, capillaries, and venules, plays a pivotal role in the distribution of blood throughout tissues, with capillaries acting as the primary sites for oxygen and nutrient delivery as well as waste product removal. A critical component of the microcirculation is the vascular pericyte (PC), which is essential for angiogenesis and the regulation of microvascular biomechanics. This thesis focuses on the cerebrovascular network, particularly the cerebral microcirculation, and investigates the role of pericytes in maintaining blood-brain barrier (BBB) integrity and neurovascular homeostasis. In this work We highlighted the dynamic interactions between pericytes, endothelial cells, and the extracellular matrix (ECM) in the regulation of microvascular stability and BBB function. underscoring the importance of pericytes in normal physiology and disease. The work investigated the effects of biophysical cues from blood flow on cerebral microcirculation, utilizing an ex vivo murine brain slice model to investigate pericyte behavior under altered hemodynamic conditions. Findings from these experiments suggest that pericytes play an active role in capillary wall remodeling and that changes in hemodynamic forces may lead to vascular dysfunction. Additionally, we optimized a protocol for isolating and characterizing BBB capillaries, along with an analysis of the results that delivers a more precise representation of cerebrovascular structures and their responses across various research contexts. This refined methodology lays the groundwork for future studies on BBB dysfunction in neurological diseases like Alzheimer's and stroke. The thesis also includes an in-depth examination of pericyte morphology and its heterogeneity, and their interactions with the ECM, We believe these approaches offer highly valuable, complementary techniques for characterizing pericytes and gaining insight into their role in the development, maturation, and dysfunction of the microvasculature. The insights gained from this work contribute to a more comprehensive understanding of the molecular and biomechanical mechanisms governing cerebrovascular function. As such, this thesis lays the groundwork for future studies aimed at developing therapeutic interventions targeting pericyte function and BBB integrity, with implications for treating a variety of neurological disorders.","abstract_has_math":false,"creators":["Abdelazim, Hanaa Habib Mohamed"],"institution":"Virginia Tech","degree_name":"Doctor of Philosophy","degree_level":"doctoral","degree_discipline":"Translational Biology, Medicine and Health","degree_department":"Graduate School","school":null,"contributors":[],"advisors":[],"committee_chairs":["Chappell, John Christopher"],"committee_members":["Lamouille, Samy","Fox, Michael A.","Smyth, James"],"year":2025,"date_issued":"2025-08-07","date_published":"2025-08-07","updated_at":"2026-07-22T22:20:23Z","subjects":["Blood-brain barrier","pericyte","endothelial cell","extracellular matrix","Claudin5","Endothelin-1","Vitronectin"],"languages":["en"],"rights":["In Copyright"],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["vt_gsexam:43232"],"render_values":[{"text":"vt_gsexam:43232","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/10919/137105","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.committeechair","label":"Committee Chair","values":["Chappell, John Christopher"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Lamouille, Samy","Fox, Michael A.","Smyth, James"]},{"key":"dc:contributor.department","label":"Department","values":["Graduate School"]},{"key":"dc:creator","label":"Author","values":["Abdelazim, Hanaa Habib Mohamed"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-08-08T08:00:35Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-08-08T08:00:35Z"]},{"key":"dc:date.issued","label":"Date","values":["2025-08-07"]},{"key":"dc:publisher","label":"Institution","values":["Virginia Tech"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Translational Biology, Medicine and Health"]},{"key":"thesis:degree_level","label":"Degree Level","values":["doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Virginia Polytechnic Institute and State University"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Blood-brain barrier","pericyte","endothelial cell","extracellular matrix","Claudin5","Endothelin-1","Vitronectin"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["In Copyright"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://rightsstatements.org/vocab/InC/1.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["vt_gsexam:43232"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10919/137105"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["ABSTRACT The microcirculation, encompassing terminal arterioles, capillaries, and venules, plays a pivotal role in the distribution of blood throughout tissues, with capillaries acting as the primary sites for oxygen and nutrient delivery as well as waste product removal. A critical component of the microcirculation is the vascular pericyte (PC), which is essential for angiogenesis and the regulation of microvascular biomechanics. This thesis focuses on the cerebrovascular network, particularly the cerebral microcirculation, and investigates the role of pericytes in maintaining blood-brain barrier (BBB) integrity and neurovascular homeostasis. In this work We highlighted the dynamic interactions between pericytes, endothelial cells, and the extracellular matrix (ECM) in the regulation of microvascular stability and BBB function. underscoring the importance of pericytes in normal physiology and disease. The work investigated the effects of biophysical cues from blood flow on cerebral microcirculation, utilizing an ex vivo murine brain slice model to investigate pericyte behavior under altered hemodynamic conditions. Findings from these experiments suggest that pericytes play an active role in capillary wall remodeling and that changes in hemodynamic forces may lead to vascular dysfunction. Additionally, we optimized a protocol for isolating and characterizing BBB capillaries, along with an analysis of the results that delivers a more precise representation of cerebrovascular structures and their responses across various research contexts. This refined methodology lays the groundwork for future studies on BBB dysfunction in neurological diseases like Alzheimer's and stroke. The thesis also includes an in-depth examination of pericyte morphology and its heterogeneity, and their interactions with the ECM, We believe these approaches offer highly valuable, complementary techniques for characterizing pericytes and gaining insight into their role in the development, maturation, and dysfunction of the microvasculature. The insights gained from this work contribute to a more comprehensive understanding of the molecular and biomechanical mechanisms governing cerebrovascular function. As such, this thesis lays the groundwork for future studies aimed at developing therapeutic interventions targeting pericyte function and BBB integrity, with implications for treating a variety of neurological disorders."]},{"key":"dc:description.abstractgeneral","label":"General Abstract","values":["GENERAL AUDIENCE ABSTRACT The microcirculation, which includes small blood vessels like arterioles, capillaries, and venules, is crucial for delivering oxygen and nutrients to tissues and removing waste products. Capillaries, in particular, are the primary sites for these exchanges. A key cell type in this system is the vascular pericyte (PC), which plays a vital role in blood vessel growth and the regulation of blood vessel function. This thesis focuses on the blood vessels in the brain, specifically the brain's small blood vessels, and looks at how pericytes help maintain the integrity of the blood-brain barrier (BBB) and overall brain health. In this study, we explored how pericytes interact with other cells in the blood vessels, like endothelial cells, and the surrounding tissue structure, known as the extracellular matrix (ECM), to help keep blood vessels stable and the blood-brain barrier working properly. We also examined how changes in blood flow affect pericytes, using a special lab model with brain tissue from mice. Our results suggest that pericytes play an active role in reshaping blood vessel walls, and changes in blood flow can lead to problems with blood vessel function. Additionally, we developed a better method for isolating and studying the blood vessels in the brain, which provides a more accurate picture of how these blood vessels respond to changes in metabolism and blood flow. This improved technique can help future research on brain blood vessel dysfunction in conditions like Alzheimer's disease and stroke. The thesis also includes a detailed study of pericyte structure and how they vary from one another, as well as their interactions with the ECM, emphasizing their important role in keeping blood vessels stable, remodeling them, and possibly contributing to diseases. The findings from this work help us better understand the molecular and mechanical processes that control how the blood vessels in the brain function. This research sets the stage for future studies that could lead to treatments aimed at improving pericyte function and protecting the blood-brain barrier, which may help in the treatment of a range of brain-related diseases."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Doctor of Philosophy"]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["ETD"]},{"key":"dc:title","label":"Title","values":["Pericyte and Endothelial Cell Responses within Murine Cerebral Capillaries After Blood Flow Cessation"]}]}],"canonical_facts":{"dc:contributor.committeechair":["Chappell, John Christopher"],"dc:contributor.committeemember":["Lamouille, Samy","Fox, Michael A.","Smyth, James"],"dc:contributor.department":["Graduate School"],"dc:creator":["Abdelazim, Hanaa Habib Mohamed"],"dc:date.accessioned":["2025-08-08T08:00:35Z"],"dc:date.available":["2025-08-08T08:00:35Z"],"dc:date.issued":["2025-08-07"],"dc:description.abstract":["ABSTRACT The microcirculation, encompassing terminal arterioles, capillaries, and venules, plays a pivotal role in the distribution of blood throughout tissues, with capillaries acting as the primary sites for oxygen and nutrient delivery as well as waste product removal. A critical component of the microcirculation is the vascular pericyte (PC), which is essential for angiogenesis and the regulation of microvascular biomechanics. This thesis focuses on the cerebrovascular network, particularly the cerebral microcirculation, and investigates the role of pericytes in maintaining blood-brain barrier (BBB) integrity and neurovascular homeostasis. In this work We highlighted the dynamic interactions between pericytes, endothelial cells, and the extracellular matrix (ECM) in the regulation of microvascular stability and BBB function. underscoring the importance of pericytes in normal physiology and disease. The work investigated the effects of biophysical cues from blood flow on cerebral microcirculation, utilizing an ex vivo murine brain slice model to investigate pericyte behavior under altered hemodynamic conditions. Findings from these experiments suggest that pericytes play an active role in capillary wall remodeling and that changes in hemodynamic forces may lead to vascular dysfunction. Additionally, we optimized a protocol for isolating and characterizing BBB capillaries, along with an analysis of the results that delivers a more precise representation of cerebrovascular structures and their responses across various research contexts. This refined methodology lays the groundwork for future studies on BBB dysfunction in neurological diseases like Alzheimer's and stroke. The thesis also includes an in-depth examination of pericyte morphology and its heterogeneity, and their interactions with the ECM, We believe these approaches offer highly valuable, complementary techniques for characterizing pericytes and gaining insight into their role in the development, maturation, and dysfunction of the microvasculature. The insights gained from this work contribute to a more comprehensive understanding of the molecular and biomechanical mechanisms governing cerebrovascular function. As such, this thesis lays the groundwork for future studies aimed at developing therapeutic interventions targeting pericyte function and BBB integrity, with implications for treating a variety of neurological disorders."],"dc:description.abstractgeneral":["GENERAL AUDIENCE ABSTRACT The microcirculation, which includes small blood vessels like arterioles, capillaries, and venules, is crucial for delivering oxygen and nutrients to tissues and removing waste products. Capillaries, in particular, are the primary sites for these exchanges. A key cell type in this system is the vascular pericyte (PC), which plays a vital role in blood vessel growth and the regulation of blood vessel function. This thesis focuses on the blood vessels in the brain, specifically the brain's small blood vessels, and looks at how pericytes help maintain the integrity of the blood-brain barrier (BBB) and overall brain health. In this study, we explored how pericytes interact with other cells in the blood vessels, like endothelial cells, and the surrounding tissue structure, known as the extracellular matrix (ECM), to help keep blood vessels stable and the blood-brain barrier working properly. We also examined how changes in blood flow affect pericytes, using a special lab model with brain tissue from mice. Our results suggest that pericytes play an active role in reshaping blood vessel walls, and changes in blood flow can lead to problems with blood vessel function. Additionally, we developed a better method for isolating and studying the blood vessels in the brain, which provides a more accurate picture of how these blood vessels respond to changes in metabolism and blood flow. This improved technique can help future research on brain blood vessel dysfunction in conditions like Alzheimer's disease and stroke. The thesis also includes a detailed study of pericyte structure and how they vary from one another, as well as their interactions with the ECM, emphasizing their important role in keeping blood vessels stable, remodeling them, and possibly contributing to diseases. The findings from this work help us better understand the molecular and mechanical processes that control how the blood vessels in the brain function. This research sets the stage for future studies that could lead to treatments aimed at improving pericyte function and protecting the blood-brain barrier, which may help in the treatment of a range of brain-related diseases."],"dc:description.degree":["Doctor of Philosophy"],"dc:format.medium":["ETD"],"dc:identifier.other":["vt_gsexam:43232"],"dc:identifier.uri":["https://hdl.handle.net/10919/137105"],"dc:language.iso":["en"],"dc:publisher":["Virginia Tech"],"dc:rights":["In Copyright"],"dc:rights.uri":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:subject":["Blood-brain barrier","pericyte","endothelial cell","extracellular matrix","Claudin5","Endothelin-1","Vitronectin"],"dc:title":["Pericyte and Endothelial Cell Responses within Murine Cerebral Capillaries After Blood Flow Cessation"],"dc:type":["Dissertation"],"thesis:degree_discipline":["Translational Biology, Medicine and Health"],"thesis:degree_level":["doctoral"],"thesis:degree_name":["Doctor of Philosophy"],"thesis:institution_name":["Virginia Polytechnic Institute and State University"]},"updated_at":"2026-07-22T22:20:23Z"}