# The Translocator Protein (TSPO) and Intracerebral Hemorrhage

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2021 · $336,875

## Abstract

Intracerebral hemorrhage (ICH) is a stroke subtype with no effective treatment. Microglia and brain-infiltrating
macrophages play critical roles in the pathophysiology of ICH by regulating innate immune response and
hematoma resolution, the key determinants of secondary brain damage and functional recovery after ICH. Our
recent studies demonstrated an augmented expression of 18kDa translocator protein (TSPO) in microglia and
brain infiltrating macrophages after ICH. However, despite the prevalence of TSPO in neuroinflammation, the
precise functional role of TSPO in microglia and macrophages remains largely unclear. Based on our
compelling preliminary studies, our central hypothesis is that microglia and macrophage-specific expression of
TSPO modulates hemin-induced secondary brain damage and enhances hematoma resolution after ICH. To
test this, three specific aims are proposed. Aim 1. Test the hypothesis that genetic deletion of TSPO augments
secondary brain damage and exacerbates neurological outcomes after ICH. The proposed studies will include
a rigorous transgenic approach employing newly developed myeloid and microglia-specific TSPO conditional
knockouts. Aim 2. Test the hypothesis that microglia and macrophage- specific expression of TSPO enhances
hematoma resolution and pharmacological activation of TSPO improves neurological outcomes after ICH. The
proposed studies incorporating both genetic and pharmacological approaches will determine the role of TSPO
in microglia/macrophage-mediated phagocytosis and improving functional outcomes after ICH. Aim 3. Test the
hypothesis that TSPO is a feasible molecular target for the in vivo detection of activated microglia/infiltrating
macrophages after ICH. Given that the increased expression of TSPO is primarily localized to activated
microglia and infiltrating macrophages after ICH, a second generation radio labeled ligand for TSPO, [125I]iodo-
DPA-713 will be employed and TSPO-radio ligand binding will be monitored by non-invasive SPECT (Single-
photon emission computed tomography) imaging after ICH. The proposed project would identify for the first
time the precise functional role of microglia and macrophage- specific expression of TSPO in secondary brain
damage, hematoma resolution and functional outcomes after ICH. Further, the proposed preclinical studies
would also validate for the first time the therapeutic potential of targeting TSPO in improving neurological
outcomes and its diagnostic potential for neuroimaging applications after ICH.

## Key facts

- **NIH application ID:** 10167799
- **Project number:** 5R01NS107853-04
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Sangeetha Sukumari-Ramesh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $336,875
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167799

## Citation

> US National Institutes of Health, RePORTER application 10167799, The Translocator Protein (TSPO) and Intracerebral Hemorrhage (5R01NS107853-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10167799. Licensed CC0.

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