# Tocotrienol Vitamin E Against Stroke

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $344,531

## Abstract

Project Summary
Arteriogenesis refers to the growth of a functional collateral blood supply. In the brain, cerebrovascular
collaterals form networks of anastomosing arterioles that are clinically documented to perfuse stroke-affected
tissue during cerebral ischemia and attenuate brain injury. While strategies that target arteriogenesis against
acute ischemic stroke (AIS) are of significant therapeutic interest, mechanisms and a means to improve
cerebrovascular collateral circulation during AIS remain unknown. The current proposal rests on a key in vivo
observation that prophylactic supplementation of lesser-characterized natural vitamin E tocotrienol (TCT),
improves cerebrovascular collateral circulation and attenuates AIS-induced brain injury. Prophylactic TCT
supplementation therefore serves as a powerful tool to study cerebrovascular collateral biology during AIS. The
overall objective of the proposal is to characterize the effects of prophylactic TCT on cerebrovascular collateral
perfusion during stroke and to identify a mechanistic basis for TCT improvement of cerebrovascular collateral
circulation. FITC-lectin tagging of cerebrovascular collaterals is proposed for laser capture microdissection
experiments and downstream molecular analyses. This approach will enable for the first time the specific
collection of perfused cerebrovascular collaterals as well as non-patent vessels from stroke-affected tissue for
mechanistic study. The functional significance of a TCT-induced anti-proteolytic shift in cerebrovascular
collaterals is investigated. TCT induction of tissue inhibitor of metalloproteinase 1 (TIMP1) and miR-29b are
investigated as molecular targets of interest for mature collateral anastomoses in the brain. As TCT is a safe,
natural nutrient, proposal outcomes may quickly translate toward clinical applications for high-risk stroke
patients, such as those who suffered a prior stroke or a transient ischemic attack (TIA). Aim 1. Characterize the
effects of TCT on cerebrovascular collateral perfusion during acute ischemic stroke (AIS). Central Hypothesis:
Prophylactic TCT supplementation improves cerebrovascular collateral blood flow at the stroke-affected site.
Aim 2. Determine the functional significance of TCT to affect TIMP1 expression in cerebrovascular collaterals.
Central Hypothesis: TCT facilitates an optimal balance of TIMP1 expression that favors functional
cerebrovascular collateral formation. Aim 3. Examine the significance of TCT-sensitive miR-29b in
cerebrovascular collaterals. Central Hypothesis: Elevated miR-29b in response to TCT silences MMP-2 in
cerebrovascular collaterals during stroke.

## Key facts

- **NIH application ID:** 9985206
- **Project number:** 5R01NS042617-12
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Chandan K Sen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $344,531
- **Award type:** 5
- **Project period:** 2002-07-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985206

## Citation

> US National Institutes of Health, RePORTER application 9985206, Tocotrienol Vitamin E Against Stroke (5R01NS042617-12). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9985206. Licensed CC0.

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