# Sleep and Stroke

> **NIH VA I01** · HARRY S. TRUMAN MEMORIAL VA HOSPITAL · 2024 · —

## Abstract

Ischemic stroke (or Stroke) is one of the major causes of death and disability in our Veterans, and a huge
economic burden in the U.S. While Veterans in all age groups are affected by stroke, recent studies suggest that
the prevalence of stroke is higher in middle-aged Veterans returning from combat. The most common artery that
is blocked and causes stroke is the middle cerebral artery (MCA). Blockade of MCA causes ischemia that affects
major brain regions, including cortex, striatum and hippocampus. While patients suffering from stroke display
multitude of symptoms, including hemiplegia or hemiparesis, dysphagia, cognitive impairments, the most
persistent and debilitating symptoms observed in stroke patients are sleep disturbances, including insomnia,
excessive daytime sleepiness and reduced REM sleep. In addition, these sleep disturbances are associated with
worse motor outcomes and slower functional recovery post-stroke. In contrast, attenuation of sleep disturbances
in stroke patients is associated with faster recovery and promotes neurorehabilitation. Overall, sleep
disturbances are unique, novel, and modifiable treatment target that can potentially improve outcomes in stroke
patients, provided that we understand the neuroanatomical substrates responsible for sleep disturbances.
However, the paucity of animal models mimicking sleep disturbances in human stroke is the major limiting factor.
Development of appropriate animal models will enhance our understanding towards the underlying sleep-wake
substrates and mechanisms affected by stroke and help in the development of novel and targeted therapeutic
strategies to treat sleep disturbances and accelerate recovery and rehabilitation post-stroke.
Recently, we have observed that 1h of middle cerebral artery occlusion (MCAO) in middle-aged (9 - 12 months)
C57BL/6J mice mimics major symptoms of human stroke including altered sleep-wake rhythm along with
sensorimotor and cognitive deficits. We propose to use this mouse model along with a combination of
multidisciplinary approaches, such as behavioral (sleep deprivation), pharmacological (orexin receptor
antagonist) and novel non-traditional (Designer Receptor Exclusively Activated by Designer Drug; DREADD), to
test our hypothesis “Stroke disrupts sleep homeostasis and circadian processes to cause chronic sleep
disturbances that are responsible for preventing post-stroke recovery and rehabilitation.”
Two aims are designed:
Aim 1: proposes that stroke in mice will disrupt sleep homeostasis and altered circadian genes expression in
select brain regions (but not in suprachiasmatic nucleus) to cause circadian desynchrony resulting in a) sleep
disturbances observed in human stroke patients as evident by excessive daytime sleepiness during the active
(dark) period coupled with insomnia-like symptoms (reduced quality and quantity of sleep) and reduced REM
sleep during the light (sleep) period, b) sensorimotor, memory and cognitive deficits and c) altered syn...

## Key facts

- **NIH application ID:** 10698744
- **Project number:** 1I01BX006240-01
- **Recipient organization:** HARRY S. TRUMAN MEMORIAL VA HOSPITAL
- **Principal Investigator:** MAHESH M THAKKAR
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10698744

## Citation

> US National Institutes of Health, RePORTER application 10698744, Sleep and Stroke (1I01BX006240-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10698744. Licensed CC0.

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