# Chronic Stress and Anemia Recovery following Major Trauma

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2021 · $524,260

## Abstract

Abstract
Injury-associated anemia develops in patients suffering major trauma and remains persistent when followed by
critical illness. Currently, the only available treatment is blood transfusions. In the initial period of this award, we
demonstrated that bone marrow erythropoietic dysfunction was linked to a hyperadrenergic state and that with
critical illness and chronic stress this hyperadrenergic state is prolonged. We also described a novel critical illness
rodent model that combined lung contusion, hemorrhagic shock and chronic stress that led to persistent anemia on
day seven following initial injury. The prolonged adrenergic stimulation that occurred with chronic stress following
injury and hemorrhagic shock worsened erythropoietic dysfunction, reduced the growth of erythroid progenitors, and
exaggerated the mobilization of hematopoietic progenitors from the bone marrow. In addition, chronic stress led to
the combined deficit of reduced iron availability due to hepcidin activation and reduced bone marrow erythropoietin
receptor expression associated with an ineffective erythropoietin response that accompanied injury-associated
anemia. These findings were confirmed in bone marrow obtained from severely injured trauma patients. In addition,
we also demonstrated that we could improve erythropoietic function in our rodent model with either propranolol or
clonidine, both agents act to reduce the effects of norepinephrine through two different mechanisms. The
mechanistic studies proposed in this application are the natural extension of our recent findings and will test if
chronic stress and prolonged adrenergic stimulation following injury and hemorrhagic shock are directly responsible
for the persistence of injury-associated anemia with impaired differentiation and maturation of erythroid cells, and if
reduction of chronic stress can improve anemia and alter recovery. To accomplish this, there are three specific
aims: 1) To delineate if long term chronic stress results in a persistent inflammatory milieu that further impairs
recovery of injury-associated anemia; 2) To determine if alterations in the erythropoietin receptor or hepcidin or
stress-related genomic changes in erythroid differentiation is the primary event following injury and chronic stress
contributing to persistent injury-associated anemia; 3) To determine the optimal therapeutic agent to reduce chronic
stress and investigate if it leads to faster resolution of injury-associated anemia and improved recovery. The first
aim will further characterize injury-associated anemia long-term and during recovery. The second aim will determine
the how chronic stress mechanistically alters hepcidin function and stress-related genomic changes in
erythropoiesis leading to impaired differentiation and maturation of erythroid cells. The third aim will determine the
optimal therapeutic agent to reduce the hyperadrenergic state following trauma and possibly decrease the duration
of persistent inju...

## Key facts

- **NIH application ID:** 10217153
- **Project number:** 5R01GM105893-10
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** ALICIA M MOHR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $524,260
- **Award type:** 5
- **Project period:** 2013-09-24 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217153

## Citation

> US National Institutes of Health, RePORTER application 10217153, Chronic Stress and Anemia Recovery following Major Trauma (5R01GM105893-10). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10217153. Licensed CC0.

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