# Protecting endogenous recovery from the "infectious insult" in Spinal Cord Injury

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2024 · $566,089

## Abstract

Abstract
Acquired infections after spinal cord injury (SCI) constitute the main cause of death in patients. For those that
survive, acute pneumonia has been associated with significantly reduced neurological recovery. However,
proof of causality and the mechanisms underlying the blunted recovery triggered by infections remain elusive.
To analyze whether pneumonia has a causal and direct effect on the lesioned spinal cord, we expose mice
to a clinically relevant, controlled SCI-associated pneumonia (SCI-AP) embedded into a bed-to-bench
translational approach. Our experimental data demonstrate that contracting pneumonia after subacute SCI
with consecutive intraparenchymal iron deposition extending from the lesion site into spared tissue. Three
aims are proposed to answer one main and novel question: does acute pneumonia exacerbate spinal cord
 -AP-triggered signaling as
causal targets for neuroprotective intervention. Experiments in Aim 1 apply parabiosis models in conjunction
with serum injections to identity circulatory, humoral factors underlying SCI-AP-induced injury/disrepair.
Moreover, tracing bacterial fragments will detect passive shuttling of immunogenic bacterial
material (Bright fluorescent S. pneumoniae) across a breached blood spinal cord barrier to study possible
direct spinal cord lesion-pathogen interactions. Loss of vascular integrity will be detailed to the capillary level
to detect features of capillary fragmentation by using spinal cord tissue clearing, intravascular tracing and
3-D imaging. Aim 2 targets and its underlying IFN-1 signaling via toxic CD11b+,
CD206-- to propagate vascular damage and/or disrepair (STINGflox x LysMcre
mice). Aim 3 captures SCI-AP-induced cell-specific transcriptional changes associated with anti-microbial
immunity, such as myeloid cell-dependent effects on spinal cord endothelium to reveal novel targets for
blocking or reversing SCI-AP-induced injury/disrepair. Clinically, SCI-AP typically emerges around day 2-3
days post SCI when the patient is in the hospital. This offers a more feasible and realistic time window for
protective interventions compared to orthodox neuroprotective strategies which are limited to a short post-
SCI time-window (golden first hour(s)). If successful, data from these experiments will directly inform effective
strategies for SCI patients to i) reduce infection-associated disability and ii) protect outcome at risk.

## Key facts

- **NIH application ID:** 10981536
- **Project number:** 1R01NS135237-01A1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Jan Schwab
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $566,089
- **Award type:** 1
- **Project period:** 2024-09-20 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10981536

## Citation

> US National Institutes of Health, RePORTER application 10981536, Protecting endogenous recovery from the "infectious insult" in Spinal Cord Injury (1R01NS135237-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10981536. Licensed CC0.

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