AMBIENT OXYGEN AVAILABILITY MODULATES EXPRESSION OF VASCULAR ANGIOGENIC FACTORS AND CAPILLARY REMODELING (ANGIOPLASTICITY) IN THE MOUSE BRAIN
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Case Western Reserve University School of Graduate Studies / OhioLINK
2013
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=case1350159484 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-case13501594842021-08-03T05:19:44Z AMBIENT OXYGEN AVAILABILITY MODULATES EXPRESSION OF VASCULAR ANGIOGENIC FACTORS AND CAPILLARY REMODELING (ANGIOPLASTICITY) IN THE MOUSE BRAIN Benderro, Girriso Futara Neurobiology hypoxia hyperoxia angioplasticity angiogenesis microvascular regression HIF-¿¿ COX-2 VEGF Ang-2 Fluctuation in tissue oxygen tension results in systemic physiological, metabolic, and vascular changes in order to maintain cellular homeostasis. Using C57BL/6J mice exposed to normoxia, hypoxia or hyperoxia, we studied the systemic physiological and brain microvascular adaptive changes in response to fluctuations in atmospheric oxygen level. In the first part of this project, we determined the relative time course of capillary angiogenesis and regression including expression of some of the signaling factors involved in the process during chronic hypoxia and subsequent re-oxygenation. Results indicated that expressions of hypoxia inducible factor-1¿¿ (HIF-1¿¿), vascular endothelial growth factor (VEGF) and erythropoietin (EPO) were increased during hypoxic exposure and diminished during subsequent re-oxygenation. However, expressions of cyclooxygenase-2 (COX-2) and angiopoietin-2 (Ang-2) were elevated during hypoxia as well as re-oxygenation. Significantly increased capillary density at the end of the 3rd week of hypoxia regressed back toward normoxic baseline during re-oxygenation.In the second part of this study, we analyzed adaptive changes during chronic hyperoxia. Results showed accumulation of HIF-1 and 2¿¿, and increased expression of EPO, COX-2 and Ang-2. Conversely, VEGF, and VEGF receptor-2, PPAR-¿¿¿ coactivator (PGC-1¿¿) and prolylhydroxylase domain-2 (PHD-2) expressions were decreased. VEGF mRNA level was diminished but there was no change in HIF-1¿¿ mRNA and von Hippel Lindau (VHL) protein expression during hyperoxia, with capillary density significantly diminished by the 3rd week of hyperoxia. In the third part of the study, we analyzed whether aging affects systemic and cerebral angiogenic adaptive changes in response to prolonged hypoxia in the mouse. Our data showed that during hypoxia, accumulation of HIF-1¿¿ was attenuated, and VEGF expression was decreased in the cerebral cortex of aged mice. Conversely, COX-2, Ang-2, and PGC-1¿¿ protein upregulation were not affected in the aged cohort. Despite an initial delay in cerebral angiogenic response in aged mice, no significant differences were observed in the capillary density between the young and aged mice cerebral cortex in normoxia and throughout the 2nd and 3rd weeks of hypoxia. Overall, we can conclude that the brain capillary density is a continuously adjusted variable with tissue oxygen availability as a critical controlling modulator. 2013-03-07 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1350159484 http://rave.ohiolink.edu/etdc/view?acc_num=case1350159484 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Neurobiology hypoxia hyperoxia angioplasticity angiogenesis microvascular regression HIF-¿¿ COX-2 VEGF Ang-2 |
| spellingShingle |
Neurobiology hypoxia hyperoxia angioplasticity angiogenesis microvascular regression HIF-¿¿ COX-2 VEGF Ang-2 Benderro, Girriso Futara AMBIENT OXYGEN AVAILABILITY MODULATES EXPRESSION OF VASCULAR ANGIOGENIC FACTORS AND CAPILLARY REMODELING (ANGIOPLASTICITY) IN THE MOUSE BRAIN |
| author |
Benderro, Girriso Futara |
| author_facet |
Benderro, Girriso Futara |
| author_sort |
Benderro, Girriso Futara |
| title |
AMBIENT OXYGEN AVAILABILITY MODULATES EXPRESSION OF VASCULAR ANGIOGENIC FACTORS AND CAPILLARY REMODELING (ANGIOPLASTICITY) IN THE MOUSE BRAIN |
| title_short |
AMBIENT OXYGEN AVAILABILITY MODULATES EXPRESSION OF VASCULAR ANGIOGENIC FACTORS AND CAPILLARY REMODELING (ANGIOPLASTICITY) IN THE MOUSE BRAIN |
| title_full |
AMBIENT OXYGEN AVAILABILITY MODULATES EXPRESSION OF VASCULAR ANGIOGENIC FACTORS AND CAPILLARY REMODELING (ANGIOPLASTICITY) IN THE MOUSE BRAIN |
| title_fullStr |
AMBIENT OXYGEN AVAILABILITY MODULATES EXPRESSION OF VASCULAR ANGIOGENIC FACTORS AND CAPILLARY REMODELING (ANGIOPLASTICITY) IN THE MOUSE BRAIN |
| title_full_unstemmed |
AMBIENT OXYGEN AVAILABILITY MODULATES EXPRESSION OF VASCULAR ANGIOGENIC FACTORS AND CAPILLARY REMODELING (ANGIOPLASTICITY) IN THE MOUSE BRAIN |
| title_sort |
ambient oxygen availability modulates expression of vascular angiogenic factors and capillary remodeling (angioplasticity) in the mouse brain |
| publisher |
Case Western Reserve University School of Graduate Studies / OhioLINK |
| publishDate |
2013 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=case1350159484 |
| work_keys_str_mv |
AT benderrogirrisofutara ambientoxygenavailabilitymodulatesexpressionofvascularangiogenicfactorsandcapillaryremodelingangioplasticityinthemousebrain |
| _version_ |
1719418568847654912 |