# Brain Injury Treatment by Modulation of Hemodynamics with Blood Soluble Drag Reducing Molecules

> **NIH NIH R01** · LOVELACE BIOMEDICAL & ENVIRONMENTAL RESEARCH INSTITUTE · 2020 · $449,779

## Abstract

Abstract
Traumatic brain injury (TBI) is a major health problem, representing a third of all injury-related deaths in the
United States and 70% of long-term disabilities in survivors. Decades of TBI research focused almost exclusively
on neuroprotective strategies, has failed to develop any therapeutics for clinical treatment. One less explored
potential target is the cerebral circulation. In TBI, there is increasing recognition that the peri-contusional areas
of TBI suffer microvascular failure and diffusional hypoxia and edema. Our studies on microvascular shunts
(MVS) with high intracranial pressure (ICP) corroborate microcirculatory failure. We propose here modulation of
hemodynamics with blood soluble drag reducing polymers (DRP) as a novel treatment modality for TBI that
specifically targets cerebral microcirculation and that based on physical but not pharmacological principles.
Nanomolar amounts of intravenous DRP reduce blood pressure loss in arterioles by diminishing flow separations
and microvortices at vessel bifurcations, increase precapillary pressure and the density of functioning capillaries.
Increased vascular wall shear rate may reduce transcapillary macrophage migration and inflammation. We
showed that 140 µg/kg of intravenous DRP (ED70) increased blood flow velocity in cerebral arterioles, reduced
MVS, restored perfusion in capillaries and reduced tissue hypoxia in a rat model of TBI when i.v. injected 30
minutes after the insult. The next logical step, our objective, is to perform a comprehensive study of the dose
and time-related efficacy of DRP and to examine the therapeutic mechanisms involved. Central hypothesis: DRP,
through their general dose-dependent action on cerebrovascular microcirculation, can present a unique and
effective therapy for TBI, applicable at both, early and later time. The rationale is that unlike other TBI therapies
tested thus far, the hemorheological effects of DRP are independent of tissue status in terms of tissue or vascular
receptor reactivity or sensitivity for its mechanism of action. Our long-term goal is to optimize the application of
DRP after TBI for maximal efficacy on long-term recovery and provide for the first time, a therapeutic intervention
that may be effective even if delayed hours after injury. Using the lateral fluid percussion injury TBI model in rats,
we will address two aims: 1) to study the acute dose-dependent effects of DRP on the time course and relative
changes in cerebral microvascular flow, i.e. MVS, tissue oxygenation and metabolism using in-vivo 2-photon
laser microscopy and laser speckle imaging after moderate and severe TBI; and 2) to define the optimal dose
and therapeutic time window of DRP for clinically relevant long-term outcomes and mechanisms involved using
magnetic resonance imaging, behavioral testing and histology, possible anti-inflammatory effects of rheological
modulation will be evaluated by ELISA and immunohistochemistry. To comply with NIH requiremen...

## Key facts

- **NIH application ID:** 9979985
- **Project number:** 5R01NS112808-03
- **Recipient organization:** LOVELACE BIOMEDICAL & ENVIRONMENTAL RESEARCH INSTITUTE
- **Principal Investigator:** Denis E. Bragin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $449,779
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979985

## Citation

> US National Institutes of Health, RePORTER application 9979985, Brain Injury Treatment by Modulation of Hemodynamics with Blood Soluble Drag Reducing Molecules (5R01NS112808-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9979985. Licensed CC0.

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