# Novel combinatory therapy for experimental ischemic stroke

> **NIH NIH R01** · LSU HEALTH SCIENCES CENTER · 2021 · $327,688

## Abstract

PROJECT SUMMARY / ABSTRACT
Stroke is a leading cause of death and permanent disability, with an estimated impact on public health of $73.7
billion per year in the United States. Ischemic stroke accounts for over 85% of stroke cases. Therapeutic
options for ischemic stroke are limited. Early treatment with recombinant tissue-plasminogen activator (tPA)
only benefits a fraction of patients. In addition, this treatment does not target immuno-inflammatory events
during stroke. Ischemia-reperfusion damage is associated with dysregulation of multiple neuroinflammatory
signaling pathways that causes irreversible damage to neuronal circuits resulting in the pathologies that affect
stroke survivors. Our multi-PI team with extensive, complementary, and unique expertise and access to
multiple research tools will use a rat model to investigate the efficacy of a novel approach to pharmacologically
resolve neuroinflammatory disruptions triggered by experimental ischemic stroke and thus preserve neuronal
network integrity and promote neurologic recovery. Our central hypothesis is that blocking pro-
inflammatory platelet activating factor receptor (PAFR) together with administration of docosanoids
will lead to sustained neurological recovery and protect neuronal circuits in the primary motor cortex
after ischemic stroke. Compelling preliminary data support this hypothesis. We have identified a low
molecular weight PAFR antagonist, LAU-0901, which will be administered together with the aspirin-triggered
(AT) isomer, AT-NPD1 (aspirin-triggered neuroprotectin D1), our lead docosanoid, in the studies proposed for
this application. We predict that our new experimental combination therapy that targets mechanisms of motor
circuit damage by blocking pro-inflammatory PAF signaling will reduce damage and enhance survival by
ensuring the availability of pro-resolving and neuroprotective lipid mediators following middle cerebral artery
occlusion (MCAo). We propose two specific aims: 1) To test the hypothesis that combined blocking of pro-
inflammatory PAF plus treatment with docosanoids after MCAo will lead to sustained neurological recovery,
and 2) Test the prediction that pro-homeostatic lipid mediator pathways are restored by combination treatment
for experimental ischemic stroke. The scientific premise of the proposed research is to identify key network
processes in adaptive brain plasticity, which may help to predict functional outcome and may also lead to
development of therapeutic interventions to support and promote recovery after stroke. This innovative
therapeutic approach may also be applicable to the treatment of other neurological diseases with an
inflammatory component such as Alzheimer's disease, Parkinson's disease and others.

## Key facts

- **NIH application ID:** 10093153
- **Project number:** 5R01NS104117-04
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** Nicolas G. Bazan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $327,688
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10093153

## Citation

> US National Institutes of Health, RePORTER application 10093153, Novel combinatory therapy for experimental ischemic stroke (5R01NS104117-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10093153. Licensed CC0.

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