# Mechanisms of Resveratrol Induced Neuroprotection

> **NIH NIH R21** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $191,875

## Abstract

PROJECT SUMMARY
 Cerebral ischemia, most notably in the form of stroke, is one of the leading causes of death and disability.
Unfortunately, the utilization of tissue plasminogen activator is the only approved therapy for stroke, with limited
application potential. Clinical trials testing post-stroke neuroprotective agents have not been successful. Thus,
the identification of prophylactic strategies able to induce endogenous neuroprotective mechanisms has high
potential for stroke therapy. The therapeutic potential of preconditioning paradigms, in which brief episodes of a
sublethal ischemic insult induce robust protection against subsequent ischemic injuries, has been repeatedly
demonstrated. Our studies suggests that resveratrol preconditioning can induce a chronic ischemic tolerance
that lasts for at least 2 weeks in vivo.
 The main objective of this proposal is to determine the mechanistic basis of neuroprotection afforded by
resveratrol induced preconditioning to help us identify innovative therapeutic strategies that prevent or at least
reduce neuronal damage in susceptible patients. We have shown that resveratrol emulated ischemic
preconditioning (IPC) in brain in a Sirt1 dependent manner. A major observation emerging from our studies is
that resveratrol upregulate BDNF levels. We hypothesize that the transcriptional regulator MeCP2 mediates, at
least in part, the neuronal transcriptional responses to Resveratrol. In aim 1, we will test the MeCP2 dependence
of RPC-induced chronic ischemic tolerance. The neuroprotective effect of resveratrol will we assessed in control
mice and a tamoxifen-inducible neuron-specific Mecp2 knockout mice which will be subjected to focal cerebral
ischemia by middle cerebral artery occlusion (MCAo). Aim 2 will assess the ability of RPC to modify MeCP2
dependent gene regulation. For these experiments we will employ in vivo (mouse brain) and ex vivo (organotypic
cortical slice cultures) experiments to assay the effect of resveratrol administration on posttranslational
modifications of MeCP2, the binding of MeCP2 to chromatin and to its cognate partners.
 Identification of the mechanisms by which long-lasting neuroprotection elicited by resveratrol will have
implications not only in stroke and several other forms of ischemia, such as cardiac arrest, but also other
neurological disorders with similar pathology.

## Key facts

- **NIH application ID:** 10003155
- **Project number:** 5R21AT010388-02
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** MIGUEL A PEREZ-PINZON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $191,875
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003155

## Citation

> US National Institutes of Health, RePORTER application 10003155, Mechanisms of Resveratrol Induced Neuroprotection (5R21AT010388-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10003155. Licensed CC0.

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