A recent study has found that uninterrupted sleep is crucial for recovery following a traumatic brain injury (TBI). The research, conducted on mice, revealed that fragmented sleep led to a reduction in rapid-eye-movement (REM) sleep and increased fatigue. Mice with TBI who experienced interrupted sleep were unable to compensate for the loss of REM sleep, unlike uninjured mice.
REM sleep plays an important role in consolidating and processing new information and is linked to better concentration and mood regulation. Its loss can negatively affect brain and cellular function.
"I think sleep has gone underappreciated as a key determinant of traumatic brain injury outcomes for a long time," said Olga Kokiko-Cochran, senior author of the study, investigator in the Chronic Brain Injury Program and the Institute of Brain, Behavior, and Immunology at The Ohio State University, and associate professor of neuroscience in the College of Medicine.
"A brain injury doesn't occur in isolation. We have to think about the recovery environment and acknowledge that there are effects of external stimuli," she added. "We set up the paper to think about recovery in a hospital, rehabilitation or even a home setting where there are lots of things in the environment that might influence someone's sleep – and oftentimes those may go unrecognized or unnoticed or even downplayed as to how important they could be in influencing recovery."
The findings were published recently in Experimental Neurology. The injuries studied resembled moderate TBIs such as those caused by falls.
Researchers divided mice into four groups: those with TBI exposed to either fragmented or undisturbed sleep, and control mice who underwent surgery but did not receive brain injuries. Some animals were implanted with sensors to monitor brain activity (EEG), muscle activity (EMG), body temperature, and movement over 30 days post-injury—a period comparable to several months for humans.
To simulate disrupted rest similar to what patients might experience during hospitalization or at home after injury, researchers used a moving bar across mouse cages every two minutes during their main sleeping phase.
After one week, TBI-affected mice showed reduced activity compared with controls; this decrease continued through weeks three and four. Sleep fragmentation alone also resulted in fatigue but was more severe when combined with TBI.
"Just looking at the activity alone you can't differentiate that the fatigue is worse until you look at some more nuanced statistical tests," said Christopher Cotter, co-first author of the paper and student at Ohio State's Neuroscience Graduate Program. "That's really important when we think about clinical populations – they might get sleep recordings that suggest nothing is wrong. One of the points of this analysis was to show that there are a lot of biological things happening that you may not be able to see with sleep analysis alone."
Both non-REM and REM phases were affected by interrupted rest across all groups; however, only uninjured mice compensated for lost REM after normalizing their routines post-fragmentation exposure.
"So the sham mice are compensating for the loss, but all of the animals with TBI are not compensating for that loss and they continue not compensating for the loss over the four weeks. They just lose that REM sleep and they don't get it back," Cotter explained. "We looked to see if they were sleeping more when they were not supposed to be, and the answer was no. So they just lost that sleep, and that was a really striking finding."
Data from EEG readings indicated unique deficits among injured mice subjected to fragmented rest: these animals needed more non-REM rest but did not achieve it; their persistent lack of REM during acute recovery could contribute further cognitive decline.
"Change in sleep quality really happens between one and 14 days, so that is a more vulnerable time for disruption after traumatic brain injury," Cotter noted. "There is this sensitized injury response period."
Kokiko-Cochran highlighted how continuous monitoring provided new insights: "This model of brain injury and sleep fragmentation gives us an opportunity to study things like fatigue – something understudied in the space of traumatic brain injury that can be difficult to model," she said. "It's important because many survivors have an opportunity for extended lifespans. They're surviving sometimes decades after their brain injury, but there are still persistent symptoms.
"We are trying to be conscious of the fact that people are having lots of other experiences that could influence their recovery."
The research received support from the National Institutes of Health. Additional contributors from Ohio State included Zoe Tapp (co-first author), Cindy Ren, Sam Houle, Jessica Mitsch, John Sheridan, Jonathan Godbout, Juan Peng,and Ashley Ingiosi.
