Why whales don't get brain damage when they swim

Special blood vessels in whale brains may protect them from pulses, caused by swimming, in their blood that would damage the brain, new UBC research has suggested.

There are many theories as to the exact use of these networks of blood vessels cradling a whale's brain and spine, known as 'retia mirabilia', or 'wonderful net', but now UBC zoologists believe they've solved the mystery, with computer modeling backing their predictions.

Land mammals such as horses experience 'pulses' in their blood when galloping, where blood pressures inside the body go up and down on every stride. In a new study, lead author Dr. Margo Lillie and her team have suggested for the first time that the same phenomenon occurs in marine mammals that swim with dorso-ventral movements; in other words, whales. And, they may have found out just why whales avoid long-term damage to the brain for this.

In all mammals, average blood pressure is higher in arteries, or the blood exiting the heart, than in veins. This difference in pressure drives the blood flow in the body, including through the brain, says Dr. Lillie, a research associate emerita in the UBC department of zoology. However, locomotion can forcefully move blood, causing spikes in pressure, or 'pulses' to the brain. The difference in pressure between the blood entering and exiting the brain for these pulses can cause damage.

Long-term damage of this kind can lead to dementia in human beings, says Dr. Lillie. But while horses deal with the pulses by breathing in and out, whales hold their breath when diving and swimming. "So if cetaceans can't use their respiratory system to moderate pressure pulses, they must have found another way to deal with the problem," says Dr. Lillie.

Dr. Lillie and colleagues theorized that the retia use a 'pulse-transfer' mechanism to ensure there is no difference in blood pressure in the cetacean's brain during movement, on top of the average difference. Essentially, rather than dampening the pulses that occur in the blood, the retia transfer the pulse in the arterial blood entering the brain to the venous blood exiting, keeping the same 'amplitude' or strength of pulse, and so, avoiding any difference in pressure in the brain itself.

The researchers collected biomechanic parameters from 11 cetacean species, including, fluking frequency, and input these data into a computer model.

"Our hypothesis that swimming generates internal pressure pulses is new, and our model supports our prediction that locomotion-generated pressure pulses can be synchronized by a pulse transfer mechanism that reduces the pulsatility of resulting flow by up to 97 per cent,"says senior author Dr. Robert Shadwick, professor emeritus in the UBC department of zoology.

The model could potentially be used to ask questions about other animals and what's happening with their blood pressure pulses when they move, including humans, says Dr. Shadwick. And while the researchers say the hypothesis still needs to be tested directly by measuring blood pressures and flow in the brain of swimming cetaceans, this is currently not ethically and technically possible, as it would involve putting a probe in a live whale.

"As interesting as they are, they're essentially inaccessible," he says. "They are the biggest animals on the planet, possibly ever, and understanding how they manage to survive and live and do what they do is a fascinating piece of basic biology."

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Brain damage from long stays in space

Spending a long time in space appears to cause brain damage. This is shown by a study of five Russian cosmonauts who had stayed on the International Space Station (ISS). Researchers at the University of Gothenburg are among those now presenting the results.

The study is published in the scientific journal JAMA Neurology. Its co-authors at the University, scientists from the Institute of Neuroscience and Physiology at Sahlgrenska Academy, wrote it jointly with colleagues in Moscow and Munich.

The scientists followed five male Russian cosmonauts working on the permanently manned International Space Station (ISS), which is in orbit 400 km from Earth's surface.

The adverse effects on the body of long periods in space have been known for some time. The negative changes include atrophic muscles, decreasing bone mass, deteriorating vision and altered bacterial flora in the gut.

Evidence of brain damage

Blood samples were taken from the cosmonauts 20 days before their departure to the ISS. On average, they then stayed in space for 169 days (approximately five and a half months). The participants' mean age was 49.

After their return to Earth, follow-up blood samples were taken on three occasions: one day, one week, and about three weeks respectively after landing. Five biomarkers for brain damage were analyzed. They were neurofilament light (NFL), glial fibrillary acidic protein (GFAP), total tau (T-tau), and two amyloid beta proteins.

For three of the biomarkers -- NFL, GFAP and the amyloid beta protein Aβ40 -- the concentrations were significantly elevated after the space sojourn. The peak readings did not occur simultaneously after the men's return to Earth, but their biomarker trends nonetheless broadly tallied over time.

"This is the first time that concrete proof of brain-cell damage has been documented in blood tests following space flights. This must be explored further and prevented if space travel is to become more common in the future," says Henrik Zetterberg, professor of neuroscience and one of the study's two senior coauthors.

Several studies underway

"To get there, we must help one another to find out why the damage arises. Is it being weightless, changes in brain fluid, or stressors associated with launch and landing, or is it caused by something else? Here, loads of exciting experimental studies on humans can be done on Earth," he continues.

The notion that the changes concerned may have a bearing on brain function is substantiated by changes also seen in magnetic resonance imaging (MRI) of the brain after space travel. Further support is provided by clinical tests of the men's brain function that show deviations linked to their assignments in space. However, the present study was too small to investigate these associations in detail.

Zetterberg and his coauthors at the University, scientist Nicholas Ashton and Professor Kaj Blennow, are currently discussing follow-up studies with their other fellow researchers involved in the study, and also with national and international space research institutes.

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Gut bacteria influence brain development

Extremely premature infants are at a high risk for brain damage. Researchers have now found possible targets for the early treatment of such damage outside the brain: Bacteria in the gut of premature infants may play a key role. The research team found that the overgrowth of the gastrointestinal tract with the bacterium Klebsiella is associated with an increased presence of certain immune cells and the development of neurological damage in premature babies.

Complex interplay: the gut-immune-brain axis

The early development of the gut, the brain and the immune system are closely interrelated. Researchers refer to this as the gut-immune-brain axis. Bacteria in the gut cooperate with the immune system, which in turn monitors gut microbes and develops appropriate responses to them. In addition, the gut is in contact with the brain via the vagus nerve as well as via the immune system. "We investigated the role this axis plays in the brain development of extreme preterm infants," says the first author of the study, David Seki. "The microorganisms of the gut microbiome -- which is a vital collection of hundreds of species of bacteria, fungi, viruses and other microbes -- are in equilibrium in healthy people. However, especially in premature babies, whose immune system and microbiome have not been able to develop fully, shifts are quite likely to occur. These shifts may result in negative effects on the brain," explains the microbiologist and immunologist.

Patterns in the microbiome provide clues to brain damage

"In fact, we have been able to identify certain patterns in the microbiome and immune response that are clearly linked to the progression and severity of brain injury," adds David Berry, microbiologist and head of the research group at the Centre for Microbiology and Environmental Systems Science (CMESS) at the University of Vienna as well as Operational Director of the Joint Microbiome Facility of the Medical University of Vienna and University of Vienna. "Crucially, such patterns often show up prior to changes in the brain. This suggests a critical time window during which brain damage of extremely premature infants may be prevented from worsening or even avoided."

Comprehensive study of the development of extremely premature infants

Starting points for the development of appropriate therapies are provided by the biomarkers that the interdisciplinary team was able to identify. "Our data show that excessive growth of the bacterium Klebsiella and the associated elevated ??-T-cell levels can apparently exacerbate brain damage," explains Lukas Wisgrill, Neonatologist from the Division of Neonatology, Pediatric Intensive Care Medicine and Neuropediatrics at the Department of Pediatric and Adolescent Medicine at the Medical University of Vienna. "We were able to track down these patterns because, for a very specific group of newborns, for the first time we explored in detail how the gut microbiome, the immune system and the brain develop and how they interact in this process," he adds. The study monitored a total of 60 premature infants, born before 28 weeks gestation and weighing less than 1 kilogram, for several weeks or even months. Using state-of-the-art methods -- the team examined the microbiome using 16S rRNA gene sequencing, among other methods -- the researchers analysed blood and stool samples, brain wave recordings (e.g. aEEG) and MRI images of the infants' brains.

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