# Early hematoma lysis and hemoglobin toxicity in intracerebral hemorrhage

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $547,257

## Abstract

ABSTRACT
There is much evidence that the hemoglobin released after erythrocyte lysis is a cause of brain
injury after cerebral hemorrhage. This may be related to hemoglobin or its degradation products
(e.g. iron). How to reduce such injury is important considering there are no current clinically
proven therapies for intracerebral hemorrhage. One mechanism that is involved in limiting
hemoglobin toxicity systemically is CD163, a hemoglobin scavenger receptor, which is involved
in the cellular uptake of hemoglobin when bound to haptoglobin. However, in cerebral
hemorrhage, our recent results, supported by others, indicates that some hemoglobin is
released before CD163 and other defense mechanisms are upregulated in brain (early
erythrolysis). In addition, while microglial CD163 may be beneficial in scavenging hemoglobin,
CD163 is also upregulated in neurons and is involved in inducing cell death. The aims of this
proposal are, therefore: 1) Determine the mechanisms by which early hemoglobin release from
cerebral hematomas occurs and can be reduced. 2) Examine whether CD163 is a therapeutic
target in intracerebral hemorrhage. 3) Determine the mechanisms regulating CD163 in
microglia and neurons in order to potentially manipulate those levels independently. These
experiments will involve in vivo and in vitro models of intracerebral hemorrhage in rats, mice and
pig already established in our laboratories.

## Key facts

- **NIH application ID:** 9857669
- **Project number:** 5R01NS106746-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Richard F Keep
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $547,257
- **Award type:** 5
- **Project period:** 2018-03-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857669

## Citation

> US National Institutes of Health, RePORTER application 9857669, Early hematoma lysis and hemoglobin toxicity in intracerebral hemorrhage (5R01NS106746-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9857669. Licensed CC0.

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