# Brain Metabolites, Brain Antioxidant, and Cerebral Blood Flow Deficits in Single Ventricle Heart Disease

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $234,000

## Abstract

PROJECT SUMMARY/ ABSTRACT
 Single ventricle heart disease (SVHD) adolescents show cognitive deficits (~50% subjects), affecting
academic achievement, self-care ability, quality of life, and mortality and morbidity. Brain changes appear in
areas (hippocampus, cingulate, insula, caudate, prefrontal) that mediate cognitive functions. However, the
underlying processes for brain tissue changes in SVHD are unclear, but may include hypoxemia from lower O2
saturation and reduced cerebral blood flow (CBF) from low cardiac output. Chronically low cardiac output and
lower O2 saturation are common in SVHD contributing to hypoxemia that induces oxidative stress and
mitochondrial dysfunction. Mitochondrial dysfunction alters metabolites, including the N-acetyl-aspartate (NAA;
neuronal integrity), choline (Cho; membrane metabolism), creatine (Cr; energy metabolism), and myo-inositol
(MI; astrocyte proliferation). Also, antioxidants, including glutathione (GSH) levels that play a significant role
against oxidative stress, regulate neuronal/cellular protection from excessive reactive oxygen species. However,
regional brain metabolites and antioxidant status in SVHD is unknown that can be examined with the 3D Echo
Planar Spectroscopic Imaging (3D EPSI) and the MEshcher–GArwood Point RESolved Spectroscopy (MEGA-
PRESS). In addition, CBF is highly dependent on cardiac output, and lower cardiac output can result to reduced
CBF, which has not been reported after completed staged surgical palliation. Impaired CBF and lower O2
saturation can further contribute to oxidative stress, leading to tissue changes in cognitive control areas, affecting
associated functions. Regional brain CBF can be assessed by arterial spin labeling imaging, O2 saturation with
pulse oximetry, and oxidative stress with serum inflammatory biomarkers. Thus, using 25 SVHD and 25 healthy
controls, the specific aims are to: 1) assess whole-brain metabolites (NAA, Cho, Cr, and MI; using 3D EPSI) and
antioxidant (GSH; using MEGA-PRESS) in SVHD and controls; 2) identify brain CBF differences, using ASL
methods, baseline O2 saturation levels, using pulse oximetry, between SVHD and controls, and relationships
between regional CBF, O2 saturation, and cognition (using the Wide Range Assessment of Memory and Learning
2) in SVHD patients; and 3) examine inflammatory serum biomarkers in SVHD and controls, and correlate those
markers with brain metabolites, CBF, and O2 saturation values in SVHD subjects. In summary, mitochondrial
and oxidative stress mechanisms contributing to changes in brain metabolites and antioxidant, reduced CBF in
cognitive regulatory areas, and serum inflammatory biomarkers, as well as links among these measures in SVHD
patients will be examined. The outcomes from this R21 exploratory study will have significant implications on
identification of treatments for rescue/restore brain tissue that might include strategies to increase NAA,
antioxidant, and Cr levels, as well as improve CBF, an...

## Key facts

- **NIH application ID:** 10644553
- **Project number:** 1R21NS131850-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Rajesh Kumar
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $234,000
- **Award type:** 1
- **Project period:** 2023-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10644553

## Citation

> US National Institutes of Health, RePORTER application 10644553, Brain Metabolites, Brain Antioxidant, and Cerebral Blood Flow Deficits in Single Ventricle Heart Disease (1R21NS131850-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10644553. Licensed CC0.

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