# Deregulation of Sleep/Wake Homeostasis by Binge Alcohol Use Following Traumatic Brain Injury

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2023 · $181,094

## Abstract

SUMMARY
 The sleep/wake cycle is regulated by the brain’s master circadian clock. Sleep disturbance
is common in the general population and prominent in patients of neuropathological diseases.
Notably, binge alcohol use (BAU) and traumatic brain injury (TBI) represent two of the strongest
environmental risk factors for neurological disabilities. While cognitive deficits remain the
cardinal manifestation of BAU/TBI pathology, non-cognitive homeostatic abnormalities are an
integral part of the disease. A common symptom in TBI and BAU is sleep/wake disturbance,
especially later in life, which often precedes cognitive decline to drive pathology and contributes
to cognitive dysfunction. Thus, sleep/wake homeostasis can be both a culprit and target for
therapeutic intervention, but represents a major missed opportunity not only in basic research
but also for clinical practice. This is due to the limited understanding of the cause-effect between
chronic TBI/ BAU pathology and circadian/sleep dysfunction. Recent studies (including our own)
show that the proinflammatory NF-kB pathway, a key driver of inflammation, directly interacts
with the core clock component BMAL1 and interferes with clock function across cell and tissue
types and in locomotor activity rhythms. Further, NF-kB activation also alters sleep quantity and
quality. These findings, together with the well-recognized sleep-neuroimmune interactions,
support our central hypothesis that TBI/BAU comorbid neuroinflammation and neuropathology
cause circadian and sleep disruption. The proposed research will determine for the first time the
lifelong timeline (acute, subacute, chronic) of TBI/BAU neuropathology and sleep dysfunction,
which will allow us to identify the key time windows of pathogenesis and sleep/wake
phenotypes. For this, we will combine neuropathological analysis with non-invasive longitudinal
sleep assays. This study will lay the groundwork for future molecular and genomic studies on
how TBI and BAU induce neuroinflammation and how neuroinflammation impacts circadian and
sleep homeostasis. This research will have broad implications in a number of neuropathological
conditions that have an inflammatory component.

## Key facts

- **NIH application ID:** 10683216
- **Project number:** 5R21AA029785-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Andrew C. Liu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $181,094
- **Award type:** 5
- **Project period:** 2022-08-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10683216

## Citation

> US National Institutes of Health, RePORTER application 10683216, Deregulation of Sleep/Wake Homeostasis by Binge Alcohol Use Following Traumatic Brain Injury (5R21AA029785-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10683216. Licensed CC0.

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