# Brain-immune crosstalk in myocardial infarction

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $747,449

## Abstract

Brain-immune crosstalk in myocardial infarction
Project Summary
Myocardial infarction (MI) remains a leading cause of death worldwide and even survivors suffer from reduced
quality of life, increased hospitalization rates, high health care costs, and lower life expectancy. Decades of
research have improved primary prevention as well as interventional and drug therapies, but the clinical
problem for MI patients remains huge, particularly regarding aspects of post-MI healing. While some patients
develop a stable scar with adaptive remodeling of the surviving myocardium and a compensated cardiac
function for many years, other patients with comparable extent of initial damage rapidly develop ischemic heart
failure with extremely poor prognosis. Furthermore, an MI triggers a vicious inflammatory cycle of further
atherosclerosis acceleration, increasing the risk for subsequent ischemic events. Various studies have shown
that the immune system plays a critical role in these processes. An MI activates multiple sensory systems of
the brain, including pain, stress, and autonomic centers, as well as hypothalamic and brainstem sensors of
inflammation and hemodynamics. It was recently described that distinct brain regions control large scale
leukocyte shifts and functional alterations during episodes of acute stress (Poller et al., Nature 2022). How
different brain centers orchestrate the immune response to an MI and whether such neuro-immune axes can
be therapeutically harnessed to optimize post-MI inflammation and healing via targeted non-invasive brain
interventions is unknown. This project combines state-of-the-art tools of neuroscience, cardiology, and
immunology to comprehensively explore how an MI alters regional brain activity and how different brain
centers in turn shape the course of MI healing. Aim 1 combines interruption of different sensory input branches
with iDISCO cFos ClearMap histology, fiber photometry, and retrograde tracing to map MI-induced alterations
in neuronal circuit activity. Preliminary data show strongly altered neuronal firing after an MI. Aim 2 elucidates
the effects of MI-activated brain centers on the peripheral immune response after an MI. Preliminary data show
that ablation of stress centers in the brain increases post-MI leukocytosis in bone marrow and heart, whereas
chemogenetic stimulation of hypothalamic CRH neurons after an MI strongly reduces myocardial inflammation,
which is known to correlate with better functional outcomes. Aim 2 combines different MI models with an
established set of gain and loss-of-function interventions, including chemogenetics, optogenetics, viral tracing,
brain-region specific KO mice, and cell-type specific stress hormone receptor KO mice to investigate how
different brain regions contribute to post MI inflammation and healing. Finally, Aim 3 integrates gained insights
and focuses on blocking detrimental while enhancing beneficial aspects of neuro-immune signaling, e.g. by
dynamically manipu...

## Key facts

- **NIH application ID:** 11123770
- **Project number:** 7R01HL168090-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Wolfram Christian Poller
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $747,449
- **Award type:** 7
- **Project period:** 2023-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11123770

## Citation

> US National Institutes of Health, RePORTER application 11123770, Brain-immune crosstalk in myocardial infarction (7R01HL168090-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/11123770. Licensed CC0.

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