# Role of Myeloid And CD4+ T Immune Cells in Post-Traumatic Plasticity

> **NIH NIH R01** · J. DAVID GLADSTONE INSTITUTES · 2024 · $71,820

## Abstract

PROJECT SUMMARY/ABSTRACT
Traumatic brain injury (TBI) impacts millions of Americans each year and can lead to cognitive dysfunction,
difficulty with sensory processing, sleep disruption, and the development of epilepsy. One common neural
outcome of TBI is the development of electrophysiological abnormalities that can lead to post-traumatic epilepsy
(PTE) or disruptions in sleep architecture. However, the mechanisms by which these neurological deficits arise
as a consequence of TBI remain poorly understood.
Preliminary evidence indicates that inflammation contributes to the electrophysiological abnormalities that
underlie PTE and sleep disruption in a mouse model of moderate TBI. Indeed, TBI is characterized by both the
activation of glial cells like astrocytes and microglia and by the infiltration of peripheral immune cells like
monocyte-derived macrophages and T cells. While neuroinflammation occurs immediately in the cortical region
of acute injury, secondary neuroinflammation develops slowly in the ipsilateral thalamus, presumably as a result
of loss of intimate reciprocal connections between cortex and thalamus. Because the cortico-thalamo-cortical
(CTC) circuit plays a key role in cognition, sleep, and seizures, which are all impacted by TBI, the delayed neural
plasticity in this circuit is a good model for teasing apart the interaction between the immune cells and neural
circuits after TBI.
The role of peripheral immune cells is particularly understudied in the context of TBI-derived electrophysiological
deficits like PTE and sleep disruption. Here we use a controlled-cortical impact mouse model of moderate TBI
to determine the role of delayed infiltration of monocyte-derived macrophages and T cells in secondary
neuronal loss (Aim 1), excitation/inhibition imbalance in the cortico-thalamic circuit (Aim 2), and the development
of electrographic abnormalities such as sleep disruption and PTE (Aim 3). To do so, we combine cutting-edge
tools from both neuroscience and immunology, including genetic manipulations, flow cytometry, 3D imaging of
immune-neural interactions, synaptic physiology in brain slices, and chronic wireless EEG recordings.
The goal of the project is to understand how the immune system interacts with neural circuits after TBI to cause
the development of neurological deficits. Given that there are treatments already available in clinic to block
subsets of T cells and macrophages, this study has the potential to rapidly impact how TBI is treated in human
patients.

## Key facts

- **NIH application ID:** 10986869
- **Project number:** 3R01NS121287-03S1
- **Recipient organization:** J. DAVID GLADSTONE INSTITUTES
- **Principal Investigator:** Jeanne T Paz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $71,820
- **Award type:** 3
- **Project period:** 2021-12-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10986869

## Citation

> US National Institutes of Health, RePORTER application 10986869, Role of Myeloid And CD4+ T Immune Cells in Post-Traumatic Plasticity (3R01NS121287-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10986869. Licensed CC0.

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