# New approach to sustained neuroprotection and enhanced recovery following acute ischemic stroke

> **NIH NIH RF1** · OHIO STATE UNIVERSITY · 2022 · $1,693,719

## Abstract

Ischemic stroke is a devastating health problem, affecting approximately 795,000 patients in the US every year,
making it one of the leading causes of death and disability in the country. Recent clinical advances have shown
great promise in acute stroke therapy, with the use of mechanical endovascular thrombectomy (EVT), with or
without standard of care thrombolysis, significantly improving outcomes. Despite these promising advances,
long-term neurologic sequelae persist in the post-stroke patient population. Therefore, the use of neuroprotective
agents in combination with current methods of reperfusion provides renewed hope for the improvement of stroke
outcomes. Indeed, >1000 drugs have been shown to reduce stroke injury in experimental stroke models, but
have failed to translate to clinical benefit. The Stroke Therapy Academic Industry Roundtable (STAIR) convened
in 1999 and provided important guidelines to improve the rigor of pre-clinical models to improve translational
success. More recently, STAIR IX-X provided updates in light of endovascular therapy, advising increased
research into adjunct therapies to be combined with EVT reperfusion. The current study is a pre-clinical study
that follows the STAIR criteria to characterize a novel neuroprotectant to be utilized in combination with EVT
following large vessel occlusion (LVO).
 The STAIR group identified multiple factors contributing failure to translate, chief among them being over-
reliance on acute histological measurements of outcome and poor correspondence between experimental and
clinical study designs. To address long-term functional outcomes in our rodent model, we have moved beyond
measurements of motor deficits and add cognitive recovery to our outcome measures to assess therapies that
may provide real-world improvements in ‘quality of life’ outcomes. Experimental evidence from our group, and
others, show that tMCAo induces synaptic derangements in various brain regions, including the hippocampus.
This, coupled with the increasing evidence of cognitive impairments and memory loss following AIS (post-stroke
cognitive impairment: PSCI), makes synaptic dysfunction (synaptoprotection) a novel new target for
neuroprotective strategies.
 We have developed a drug that 1) provides acute neuroprotection and 2) causes sustained
synaptoprotection that enhances long-term cognitive recovery. We focus the current proposal on the
interaction between acute injury, delayed neuronal cell death, conversion to chronic dysfunction and therapeutic
approaches aimed at synaptoprotection to provide sustained functional benefit. The overarching premise of this
proposal is that ischemic stroke causes acute injury within the MCA territory (cortical/subcortical), delayed diffuse
neuronal injury and syanptotoxicity which contributes to the conversion to chronic cognitive decline. We will
assess dosing regimen of our novel agent, tat-M2NX, that provides optimal long-term functional recovery
following tMCAo an...

## Key facts

- **NIH application ID:** 10584833
- **Project number:** 1RF1NS127413-01A1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Paco S Herson
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,693,719
- **Award type:** 1
- **Project period:** 2022-09-19 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10584833

## Citation

> US National Institutes of Health, RePORTER application 10584833, New approach to sustained neuroprotection and enhanced recovery following acute ischemic stroke (1RF1NS127413-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10584833. Licensed CC0.

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