# Leveraging Biomarkers of Traumatic Brain Injury in Adults to Assess Cerebral Injury in Children with Sickle Cell Disease

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2020 · $210,795

## Abstract

Abstract:
 Cerebral injury is a major and debilitating complication of sickle cell disease (SCD). These injuries begin
early in the development of children with SCD and often progress throughout their lives. Types of cerebral injury
include stroke, silent cerebral infarct (SCI), transient ischemic attacks and subclinical injury. Detection of these
events can be difficult and expensive, and preventive measures are limited. There is a critical need for clinical
laboratory tests for early detection of injury in the developing brains of patients with SCD to monitor progression
and treatment effect. A previous study conducted by our team using a single analyte immunoassay that we
developed showed that glial fibrillary acidic protein (GFAP) is elevated in pediatric SCD patients vs. healthy
children, detects acute infarcts and correlates negatively with IQ. Meso Scale Diagnostics (MSD) has recently
created a multiplexed immunoassay panel for detection of biomarkers of traumatic brain injury (TBI) in adults.
This comprehensive, highly sensitive panel measures very low levels (fg-pg/mL) of known TBI biomarkers (tau,
GFAP, S100β, UCH-L1, BDNF, NSE, MMP-9, CKBB, NRGN, NPTX1, PRDX6, NF-L, MCP-1 and VILIP-1) in
plasma and sera. Our primary goal for this proposal is to determine if the blood levels of one or more of these
established TBI biomarkers correlate with brain injury confirmed by magnetic resonance imaging (MRI) or
neurocognitive assessment in children with SCD. To test the TBI biomarker panel in children with confirmed
brain injury, plasma samples from the Silent Infarct Transfusion (SIT) trial will be assayed. The SIT trial tested
whether regular blood transfusions could reduce the recurrence or progression of SCI and incidence of overt
stroke confirmed by MRI, as well as the decline in neurocognition that is seen with these injuries (as determined
by Wechsler and BRIEF assessments), in children with SCD. In this proposal, SIT screening plasma from
children with SCD that are either SCI positive (SCI+) or negative (SCI-), as adjudicated by MRI at trial entry, will
be assayed for the brain injury biomarkers that correlate with TBI in adults, to determine if they can differentiate
the SCI+ group from the SCI- group and healthy controls. Plasma from time points 0, 6, 12, 24 and 36 months
from SCI- and SCI+ participants (randomized to transfusion or observation) will be assayed to study temporal
patterns of the brain injury biomarkers over a 3-year period. We will also assess the effect of treatment
assignment (transfusion vs. observation) and look for correlations with new neurologic injuries and events that
occurred during the study, including exit MRI. Using linear regression modeling, correlations between the levels
of the biomarkers and neurocognitive assessments will be explored to identify biomarkers of neurocognitive
decline in children with SCD. This study will leverage important existing resources to find biomarkers that
measure brain injury an...

## Key facts

- **NIH application ID:** 9889976
- **Project number:** 5R21HD095024-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Emily Barron-Casella
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $210,795
- **Award type:** 5
- **Project period:** 2019-03-08 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9889976

## Citation

> US National Institutes of Health, RePORTER application 9889976, Leveraging Biomarkers of Traumatic Brain Injury in Adults to Assess Cerebral Injury in Children with Sickle Cell Disease (5R21HD095024-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9889976. Licensed CC0.

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