# Human Cerebrospinal Fluid Macrophages and Outcome in Subarachnoid Hemorrhage

> **NIH NIH R21** · FLORIDA ATLANTIC UNIVERSITY · 2022 · $178,905

## Abstract

The focus of research in aneurysmal subarachnoid hemorrhage for the last 30 years has been
on understanding the pathophysiology of vasospasm and attempts to ameliorate it.
Unfortunately, even when vasospasm is effectively treated, there is no improvement in death or
disability. Subsequently, a novel concept and more effective endpoint for clinical trials emerged
over the last 10 years: delayed cerebral ischemia (DCI), referring to new infarctions causing
focal neurological deficits. Studies have shown that the occurrence of DCI is independently
associated with morbidity, at least. The causes of DCI remains uncertain, but we believe that a
focus on the cerebral inflammatory response (CIR) to the persistent heme burden that remains
is a likely culprit for the initiation of DCI. While many independent associations for DCI exist,
none account for the CIR in any way. Perhaps a focus on expedited hematoma resolution as
well as finding some measure of the CIR to increase accuracy of DCI prediction is in order.
Based on our mouse model of SAH, we found that the tissue resident macrophages of the brain
are responsible for the majority of the CIR as well as for hematoma resolution. In our proposal,
we use each individual patient’s cerebrospinal fluid (CSF) macrophages that are of tissue
resident origin to study DCI and hematoma resolution. Specifically, we put these special
macrophages in contact with a human neuronal cell line as a way to predict whether or not a
patient might have DCI. We use flow cytometry to determine if the macrophages in the CSF are
phagocytosing significant amounts of red blood cells to determine if the hematoma will resolve
faster, and if this results in less DCI.
We believe that these studies could provide a personalized approach to predicting DCI and
hematoma resolution based on an individual’s innate immune profile. If validated in a
prospective trial, these cell-based assays could be used to empirically discover new therapeutic
targets for agents that could enhance RBC phagocytosis and reduce neuronal apoptosis by
CSF macrophages, in an example of “bedside to bench” reverse translation.

## Key facts

- **NIH application ID:** 10372925
- **Project number:** 5R21NS116337-02
- **Recipient organization:** FLORIDA ATLANTIC UNIVERSITY
- **Principal Investigator:** Khalid A. Hanafy
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $178,905
- **Award type:** 5
- **Project period:** 2021-04-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10372925

## Citation

> US National Institutes of Health, RePORTER application 10372925, Human Cerebrospinal Fluid Macrophages and Outcome in Subarachnoid Hemorrhage (5R21NS116337-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10372925. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*