Enhancing Sleep After Brain Injury Reduces Brain Damage and Cognitive Decline in Rats

Enhancing sleep after a head injury may help prevent some damage to brain cells, according to a study in rats published March 23 in the Journal of Neuroscience. Researchers at University Hospital of Zurich, Switzerland found that enhancing the slow-wave cycle of sleep after head trauma minimized damage to axons, the thin extensions that nerve cells use to send signals to other cells, and helped preserve normal brain function. The finding may offer a treatment strategy for a condition that has very few effective therapies.

Traumatic brain injury is a major cause of death and disability worldwide. While brain cells at the site of impact are damaged immediately, many more cells can perish in the hours and days after the trauma as damaged axons succumb to injury. Studies suggest that widespread axonal injury contributes to many of the long-lasting problems with learning, memory, and movement commonly associated with head injuries. Molecular waste products also build up in the brain after head injury. Recent studies indicate the brain clears out this molecular buildup during the slow-wave stage of sleep where brain activity synchronizes into high-amplitude waves.

The researchers led by Daniela Noain and Christian Baumann investigated whether enhancing slow-wave sleep after a head injury could mitigate axonal injury in rats. Twenty-five rats received a blow to the prefrontal cortex, a brain area associated with decision-making and self-control. One-third of the injured rats were sleep-deprived for short periods of time as previous studies indicate, for a brief period of time afterward, sleep deprivation enhances slow-wave sleep. Another group was treated with sodium oxybate, a drug used to induce a slow-wave sleep-like state in narcolepsy patients. A third group received placebo.

One day after injury and continuing for the next five, researchers modulated the animals’ sleep. Employing electroencephalography (EEG) recordings during treatment, they confirmed that the animals experienced slow-wave sleep enhancement as a result of treatment. Afterward, the rats took a memory test, and the team examined their brains for axonal damage, focusing on areas involved in learning and memory, including the hippocampus.

Photo of a rat brain.
Researchers found that rats receiving treatments to enhance slow-wave sleep were better able to recognize familiar objects than the untreated rats. In addition, the researchers found that levels of a biomarker for diffuse axonal injury were reduced nearly 80 percent in animals that had experienced enhanced sleep compared to untreated rats. Credit: S. B. Raymond et al/PLOS ONE.

They found that rats receiving treatments to enhance slow-wave sleep were better able to recognize familiar objects than the untreated rats. In addition, the researchers found that levels of a biomarker for diffuse axonal injury were reduced nearly 80 percent in animals that had experienced enhanced sleep compared to untreated rats.

While further study is needed, the work suggests slow-wave sleep administered immediately after a brain injury helps block axon damage and preserve normal brain function, Baumann says.

“Despite the high prevalence of traumatic brain injury worldwide, very few effective treatments exist to mitigate the persistent impairment in memory and cognitive function,” says Miranda Lim, a neurologist at Oregon Health & Science University who was not involved in the study. “This study provides important evidence that manipulating sleep may be a promising avenue to enhance recovery after TBI.”

About this neurology research

Source: Lisa Chiu – SFN
Image Source: The image is credited to S. B. Raymond et al/PLOS ONE and is licensed CC BY 2.5.
Original Research: Abstract for “Sleep Modulation Alleviates Axonal Damage and Cognitive Decline after Rodent Traumatic Brain Injury” by Marta M. Morawska, Fabian Büchele, Carlos Goncalves Moreira, Lukas L. Imbach, Daniela Noain, and Christian R. Baumann in Journal of Neuroscience. Published online March 23 2016 doi:10.1523/JNEUROSCI.3274-15.2016


Sleep Modulation Alleviates Axonal Damage and Cognitive Decline after Rodent Traumatic Brain Injury

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. It produces diffuse axonal injury (DAI), which contributes to cognitive impairment, but effective disease-modifying treatment strategies are missing. We have recently developed a rat model of closed skull TBI that reproduces human TBI consequences, including DAI and clinical sequelae such as memory impairment. Here, we investigated whether sleep modulation after trauma has an impact on DAI and memory outcome. We assessed cognition with the novel object recognition test and stained for amyloid precursor protein, a DAI marker. We found that both sleep induction and restriction acutely after TBI enhanced encephalographic slow-wave activity, markedly reduced diffuse axonal damage in the cortex and hippocampus, and improved memory impairment 2 weeks after trauma. These results suggest that enhancing slow-wave sleep acutely after trauma may have a beneficial disease-modifying effect in subjects with acute TBI.

SIGNIFICANCE STATEMENT Traumatic brain injury (TBI) is a clinically important entity. Cognitive deficits belong to the most prevalent chronic posttraumatic symptoms, most likely due to diffuse axonal injury (DAI). A growing body of evidence suggests a role of sleep in the clearance of waste products in the brain, possibly including amyloid precursor protein (APP), a marker of DAI. In this study, we provide evidence that enhancement of slow-wave oscillatory activity in the delta-frequency range decreases the APP-immunoreactivity and preserves cognitive abilities after trauma, potentially offering novel, noninvasive treatment options for traumatic injury.

“Sleep Modulation Alleviates Axonal Damage and Cognitive Decline after Rodent Traumatic Brain Injury” by Marta M. Morawska, Fabian Büchele, Carlos Goncalves Moreira, Lukas L. Imbach, Daniela Noain, and Christian R. Baumann in Journal of Neuroscience. Published online March 23 2016 doi:10.1523/JNEUROSCI.3274-15.2016

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