Junagade, Aditi
(2024)
Stroke of genius: how TGFα promotes angiogenesis & post-stroke recovery.
Undergraduate Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Strokes are a major global health issue, causing approximately 5.5 million deaths annually and imposing a financial burden on survivors and caregivers. With the aging population, stroke incidences are expected to increase significantly, and by 2030, about 4% of adults are projected to have experienced a stroke. Strokes can be classified as ischemic or hemorrhagic, with ischemic strokes, characterized by blood clots blocking blood flow to the brain, making up 87% of cases. Current treatments for ischemic strokes, such as intravenous thrombolysis and endovascular thrombectomy, have strict time constraints, leaving a substantial need for therapies that improve tissue recovery.
Post-stroke recovery involves neurogenesis, synaptogenesis, and angiogenesis, all critical for restoring function in affected brain areas. Enhancing revascularization, especially through endothelial cell proliferation and migration, is essential for creating a supportive environment for brain repair. Growth factors play vital roles in promoting post stroke brain repair. Our previous study shows that transforming growth factor alpha (TGFα) is critical in promoting white matter integrity and long-term recovery after stroke, however its role in post-stroke angiogenesis remains underexplored.
This study used TGFα knockout (KO) mouse and wild-type controls to examine the role of TGFα in post-stroke angiogenesis and functional recovery. Immunofluorescence quantification revealed that KO mice showed significantly lower endothelial cell (EC) proliferation and angiogenesis, as revealed by the reduced numbers of BrdU+CD31+ cells and Ki67+CD31+ cells, respectively. Additionally, in vitro studies using mBMECs confirmed that TGFα directly enhances EC proliferation and migration. These molecular findings align with murine behavioral tests, which demonstrated increased cognitive deficits in the KO group, correlating with the decreased angiogenesis. Collectively, these results indicate that TGFα supports endothelial network formation and vascular recovery, highlighting its therapeutic potential to promote revascularization and improve functional outcomes after ischemic stroke.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
16 December 2024 |
| Date Type: |
Publication |
| Defense Date: |
21 November 2024 |
| Approval Date: |
16 December 2024 |
| Submission Date: |
5 December 2024 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
35 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
David C. Frederick Honors College |
| Degree: |
BPhil - Bachelor of Philosophy |
| Thesis Type: |
Undergraduate Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
stroke therapies; growth factors; post-stroke vascularization; neuro-immunology; transforming growth factor; ischemia recovery |
| Date Deposited: |
16 Dec 2024 13:53 |
| Last Modified: |
16 Dec 2024 13:53 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/47183 |
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