# Reducing Infection Susceptibility by Immune Function Restoration in Spinal Cord Injury

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $367,637

## Abstract

Abstract
Acquired infections after spinal cord injury (SCI) are prevalent, constitute the main cause of death in patients
and have been identified as a modifiable risk factor associated with poor neurological and functional recovery.
Infection treatment by orthodox antibiotics is complicated by i) spectrum/efficacy gaps, ii) early development of
antibiotic resistancies, and iii) failure of antibiotics to prevent infections when applied early in patients with
acute CNS lesions. Moreover, new evidence indicates that antibiotics can impair neurological recovery, due to
their ability to cause gut dysbiosis. Improved anti-infective treatment strategies are critically needed, which take
the immune-compromised status after SCI into account. Recent data have identified unregulated sympathetic
tone originating from below the spinal cord injury site (spinally generated sympathetic nerve activity, SNA) as a
major driver of the systemic spinal cord injury immune deficiency syndrome (SCI-IDS). SNA has been
identified and independently confirmed as a mechanistic target to restore immune function in vivo. Three aims
are proposed to answer one main and novel question: Can immune function and host-defense against
pneumonia be re-established with SNA-targeting immunotrophic pharmacological neuromodulation (IPN)?
Experiments in Aim 1 will use a novel combination of FDA-approved drugs selected to promote immune
system function and reduce susceptibility to bacterial pneumonia acutely or at 4 weeks post SCI. Aim 2 will
assess the capacity of IPN to normalize different cellular SCI-IDS characteristics and the sympathetic
neuroendocrine reflex. Irrespective of SCI, infections are well-known causes of dysautonomia, which is a
pathophysiological conduit for septic conversions. Aim 3 addresses whether IPN can blunt infection-associated
autonomic dysfunction and neutralize a sepsis risk factor. If successful, data from these experiments will
directly inform effective non-antibiotic anti-infective strategies for SCI patients to reduce infection-associated
mortality and disability.

## Key facts

- **NIH application ID:** 10454352
- **Project number:** 5R01NS118200-03
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Jan Schwab
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $367,637
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454352

## Citation

> US National Institutes of Health, RePORTER application 10454352, Reducing Infection Susceptibility by Immune Function Restoration in Spinal Cord Injury (5R01NS118200-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10454352. Licensed CC0.

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