# Dynamic Neuroimmune Profiling in Patients with Acute Intracerebral Hemorrhage

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $490,960

## Abstract

Project Summary
Intracerebral hemorrhage (ICH) is a devastating type of stroke with high mortality and morbidity. Preclinical
models have identified key roles for immune responses in both acute brain injury and in functional recovery.
However, studies in human patients have been more challenging. Linking the pathophysiology seen in rodent
models to that seen in patients is critical to the successful development of immunomodulatory therapies for the
treatment of ICH.
MISTIE III is a NINDS-funded, phase-3 randomized clinical trial testing the efficacy of minimally invasive
hematoma evacuation on functional outcomes at 6 and 12 months after ICH. The trial design provides ICH
drainage samples over days 2-5 after ICH onset, precisely the time points that local inflammatory responses
contribute to injury and modulate responses that aid in repair in rodent models. This provides an unparalleled
opportunity to answer fundamental biological questions about the pathophysiology of ICH in living patients over
time.
The overall hypothesis is that blood-derived macrophages transition to alternative activation over time and this
transition is critical to resolution of inflammation via reduced cytokine signaling, enhanced phagocytosis, and
inhibition of T effector responses. Ultimately, we predict that the timing of this transition directly impacts patient
outcome.
Aim 1 will determine the cellular immune responses in the brain and peripheral blood of patients over time.
CD16+ monocytes, CD4+CD127+CD25- effector T cells, CD4+CD127-CD25+ regulatory T cells, and CD8+
cytotoxic T cells will be sorted for in depth transcriptional profiling using RNA-seq. Complementary studies will
utilize mass cytometry to comprehensively define and phenotype the leukocyte populations and track cell
populations over time. Changes in the immune responses will be integrated using systems biology
approaches and associations with patient outcome will be identified.
Aim 2 will determine how changing leukocyte phenotypes determine the effector functions of macrophages and
T cells. Using ex vivo assays using macrophages and T cells harvested from patients blood and brain at
various time points, the molecular mechanisms of phagocytosis and inhibition of effector T cell responses will
be identified.

## Key facts

- **NIH application ID:** 9948768
- **Project number:** 5R01NS097728-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** LAUREN H SANSING
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $490,960
- **Award type:** 5
- **Project period:** 2016-09-30 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948768

## Citation

> US National Institutes of Health, RePORTER application 9948768, Dynamic Neuroimmune Profiling in Patients with Acute Intracerebral Hemorrhage (5R01NS097728-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9948768. Licensed CC0.

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