# ISCHEMIC PRECONDITIONING: MECHANISMS OF NEUROPROTECTION

> **NIH NIH RF1** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2022 · $1,742,667

## Abstract

Project Summary
This proposal is a competitive renewal application which goal was to elucidate the mechanisms by which
ischemic preconditioning (IPC) affords protection against cerebral ischemia (4th cycle). Five major observations
emerged from our studies: 1) IPC, PKCε and resveratrol upregulate BDNF levels, which plays a key role in
neuroprotection; 2) IPC and PKCε activation promote significant electrophysiological alterations that lead to
ischemic tolerance; 3) resveratrol preconditioning (RPC) requires SIRT1 activity for neuroprotection, and
promotes significant gene reprograming; 4) PKCε and RSV upregulates the synaptic plasticity master regulator
Arc; and 5) RPC exhibits a prolonged window of ischemic tolerance (2 weeks) prior to middle cerebral artery
occlusion (MCAo), suggesting that this type of preconditioning exerts prolonged epigenetic modifications. From
these findings, we have gathered new preliminary data that further supports that RPC preserves synaptic
plasticity and mitigates cognitive impairments following MCAo. Since, stroke is one of the main causes of
Vascular Cognitive Impairment (VCI), which is one of the most common Alzheimer’s disease related dementias
(ADRDs), our main goal in this application is to investigate RPC mediate modifications in synaptic and cognitive
functions. Three specific aims are proposed: 1) To determine the effect of RPC on cognitive outcomes in young
and aged female and male rats; 2) To determine the mechanisms by which RPC ameliorates hippocampal
synaptic deficits following MCAo; and 3) Identification of cell specific transcriptional profiles associated with RPC
mediated hippocampal synaptic plasticity and septum nuclei preservation. These 3 aims will shed light on novel
pathways that mitigate stroke-induced cognitive deficits and may provide novel therapies to protect specifically
stroke patients from cognitive decline and may even be used for other ADRD patients, specifically those that are
affected by VCI.

## Key facts

- **NIH application ID:** 10604897
- **Project number:** 2RF1NS034773-20
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** MIGUEL A PEREZ-PINZON
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,742,667
- **Award type:** 2
- **Project period:** 1997-05-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10604897

## Citation

> US National Institutes of Health, RePORTER application 10604897, ISCHEMIC PRECONDITIONING: MECHANISMS OF NEUROPROTECTION (2RF1NS034773-20). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10604897. Licensed CC0.

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