# Understanding and Controlling Neuro-immune Interactions Following Traumatic Brain Injury

> **NIH NIH R00** · UNIVERSITY OF PENNSYLVANIA · 2024 · $249,000

## Abstract

PROJECT SUMMARY
Traumatic brain injury (TBI) affects millions of individuals annually resulting in disrupted neuronal circuitry,
persistent neurological deficits, and increased susceptibility to secondary infections. Following TBI, the
peripheral immune system (PIS) cells contribute to subsequent neuroinflammation and exacerbate
neuropathology by homing to the injured brain, associating with micropathological features, and releasing
inflammatory factors. Additionally, following TBI, the injured brain releases damage signals into the blood which
alters PIS homeostasis and functionality. Indeed, these adjustments to the PIS can result in chronic
immunodeficiency, reduced tissue regenerative capacity, impaired neurological outcomes, and an increased
mortality rate. However, the mechanisms and outcomes of how these two organ systems affect one another after
trauma has never been investigated in a clinically relevant model of diffuse TBI. Therefore, I propose to quantify
the liming, extent, and location of the infiltrating PIS in the brain after TBI, to investigate TBI-induced changes to
PIS functionality at baseline and after a clinically relevant immune challenge, and to fabricate a therapeutic
treatment strategy that will employ cells of the PIS to modulate TBI-induced neuroinflammation. Specifically,
immunomodulatory microparticles will be loaded into infiltrating immune cells and these autologous
microparticle-loaded cells will be administered intravenously after TBI. Thereafter, the therapeutic efficacy of
these cells will be quantified by characterizing the extent of infiltration, effects on the PIS, and distribution of
neuropathology. To complete this work, I propose to utilize a high-fidelity preclinical porcine model of closed-head
diffuse TBI - which is the most clinically relevant model of TBI biomechanics in use today - along with
comprehensive and quantitative PIS characterization. I hypothesize that infiltrating immune cells will localize with
micropathological features, the innate and adaptive PIS will exhibit chronic immunosuppression after TBI, and
that neuroinflammation will be mitigated when infiltrating immune cells are loaded with immunomodulatory
microparticles. Information gained from this proposal will develop a translationally-relevant treatment strategy for
TBI that could improve care of affected individuals and inform basic science questions about neuro-immune
interactions. Importantly, this research can only be completed at the University of Pennsylvania and VA Medical
Center because of unique resources, equipment, and institutional environment that is not available anywhere
else in the world. During this career development award, I will have access the injury device that induces the
porcine closed-head diffuse TBI, equipment and assays for comprehensive PIS characterization,
immunomodulatory microparticle fabrication, and large animal facilities. This career development award will offer
a unique training opportunity, answ...

## Key facts

- **NIH application ID:** 10973775
- **Project number:** 4R00NS125039-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Kathryn Leigh Wofford
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2022-09-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10973775

## Citation

> US National Institutes of Health, RePORTER application 10973775, Understanding and Controlling Neuro-immune Interactions Following Traumatic Brain Injury (4R00NS125039-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10973775. Licensed CC0.

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