By effectively pausing time itself for an individual, a state of stasis promises to enable the repair of lethal injuries, prolong life and allow for travel to distant stars.
While suspended animation may seem a fantasy, a strikingly diverse array of life has already achieved a version of it.
Through behaviours like hibernation, animals such as bears, frogs and hummingbirds can survive harsh winters, droughts, food shortages and other extreme conditions by essentially entering into biological stasis, where metabolism, heart rate and breathing slow to a crawl and body temperature drops.
Now, Harvard Medical School neuroscientists have discovered a population of neurons in the hypothalamus that controls hibernation-like behaviour, or torpor, in mice, revealing for the first time the neural circuits that regulate this state.
The team demonstrated that when these neurons are stimulated, mice enter torpor and can be kept in that state for days. When the activity of these neurons is blocked, natural torpor is disrupted.
Another study published simultaneously by the University of Tsukuba in Japan also identified a similar population of neurons in the hypothalamus.
By better understanding these processes in mice and other animal models, the authors envision the possibility of one day working toward inducing torpor in humans—an achievement that could have a vast array of applications, such as preventing brain injury during stroke, enabling new treatments for metabolic diseases or even helping NASA send humans to Mars.
“The imagination runs wild when we think about the potential of hibernation-like states in humans. Could we really extend lifespan? Is this the way to send people to Mars?” said study co-lead author Sinisa Hrvatin, instructor in neurobiology in the Blavatnik Institute at HMS.
“To answer these questions, we must first study the fundamental biology of torpor and hibernation in animals,” Hrvatin said. “We and others are doing this—it is not science fiction.”
To reduce energy expenditure in times of scarcity, many animals enter a state of torpor. Hibernation is an extended seasonal form of this. Unlike sleep, torpor is associated with systemic physiological changes, particularly significant drops in body temperature and suppression of metabolic activity.
While common in nature, the biological mechanisms that underlie torpor and hibernation are still poorly understood.
The role of the brain, in particular, has remained largely unknown, a question that drove the research efforts of Hrvatin and colleagues, including co-lead author Senmiao Sun, a graduate student in the Harvard Program in Neuroscience, and study senior author Michael Greenberg, the Nathan Marsh Pusey Professor and chair of the Department of Neurobiology in the Blavatnik Institute at HMS.
The researchers studied mice, which do not hibernate but experience bouts of torpor when food is scarce and temperatures are low.
When housed at 22 C (72 F), fasting mice exhibited a sharp drop in core body temperature and significant reduction in metabolic rate and movement. In comparison, well-fed mice retained normal body temperatures.
As mice began to enter torpor, the team focused on a gene called Fos—previously shown by the Greenberg lab to be expressed in active neurons. Labeling the protein product of the Fos gene allowed them to identify which neurons are activated during the transition to torpor throughout the entire brain.
This approach revealed widespread neuronal activity, including in brain regions that regulate hunger, feeding, body temperature and many other functions.
To see if brain activity was sufficient to trigger torpor, the team combined two techniques—FosTRAP and chemogenetics—to genetically tag neurons that are active during torpor. These neurons could then be re-stimulated later by adding a chemical compound.
The experiments confirmed that torpor could indeed be induced—even in well-fed mice—by re-stimulating neurons in this manner after the mice recovered from their initial bout of inactivity.
However, because the approach labelled neurons throughout the entire brain, the researchers worked to narrow in on the specific area that controls torpor. To do so, they designed a virus-based tool that they used to selectively activate neurons only at the site of injection.
Focusing on the hypothalamus, the region of the brain responsible for regulating body temperature, hunger, thirst, hormone secretion and other functions, the researchers carried out a series of painstaking experiments.
They systematically injected 54 animals with minute amounts of the virus covering 226 different regions of the hypothalamus, then activated neurons only in the injected regions and looked for signs of torpor.
Neurons in one specific region of the hypothalamus, known as the avMLPA, triggered torpor when activated. Stimulating neurons in other areas of the hypothalamus had no effect.
“When the initial experiment worked, we knew we had something,” Greenberg said. “We gained control over torpor in these mice using FosTRAP, which allowed us to then identify the subset of cells that are involved in the process. It’s an elegant demonstration of how Fos can be used to study neuronal activity and behavioural states in the brain.”
The team further analysed the neurons that occupy the region, using single-cell RNA sequencing to look at almost 50,000 individual cells representing 36 different cell types, ultimately pinpointing a subset of torpor-driving neurons, marked by the neurotransmitter transporter gene Vglut2 and the peptide Adcyap1.
Stimulating only these neurons was sufficient to induce rapid drops in body temperature and motor activity, key features of torpor. To confirm that these neurons are critical for torpor, the researchers used a separate virus-based tool to silence the activity of avMLPA-Vglut2 neurons. This prevented fasting mice from entering natural torpor, and in particular disrupted the associated decrease in core body temperature. In contrast, silencing these neurons in well-fed mice had no effect.
“In warm-blooded animals, body temperature is tightly regulated,” Sun said. “A drop of a couple of degrees in humans, for example, leads to hypothermia and can be fatal. However, torpor circumvents this regulation and allows body temperatures to fall dramatically. Studying torpor in mice helps us understand how this fascinating feature of warm-blooded animals might be manipulated through neural processes.”
The researchers caution that their experiments do not conclusively prove that one specific neuron type controls torpor, a complex behaviour that likely involves many different cell types. By identifying the specific brain region and subset of neurons involved in the process, however, scientists now have a point of entry for efforts to better understand and control the state in mice and other animal models, the authors said.
They are now studying the long-term effects of torpor on mice, the roles of other populations of neurons and the underlying mechanisms and pathways that allow avMLPA neurons to regulate torpor.
“Our findings open the door to a new understanding of what torpor and hibernation are, and how they affect cells, the brain and the body,” Hrvatin said. “We can now rigorously study how animals enter and exit these states, identify the underlying biology, and think about applications in humans. This study represents one of the key steps of this journey.”
The implications of one day being able to induce torpor or hibernation in humans, if ever realized, are profound.
“It’s far too soon to say whether we could induce this type of state in a human, but it is a goal that could be worthwhile,” Greenberg said. “It could potentially lead to an understanding of suspended animation, metabolic control and possibly extended lifespan. Suspended animation in particular is a common theme in science fiction, and perhaps our ability to traverse the stars will someday depend on it.”
Additional authors include Oren Wilcox, Hanqi Yao, Aurora Lavin-Peter, Marcelo Cicconet, Elena Assad, Michaela Palmer, Sage Aronson, Alexander Banks and Eric Griffith.
Police must be monitored for brain injury, argue researchers
Twenty-one police officers out of the 54 who took part in their study, all from the same police constabulary, reported having a traumatic brain injury (TBI).
“Most of the head injuries were from general life experience, such as contact or extreme sports, and some officers were ex-armed forces,” says Huw Williams, associate professor of clinical neuropsychology at the University of Exeter.
Those with TBI were more likely to have experienced post‐concussion symptoms, which was associated with greater severity of PTSD, depression and drinking to cope.
The research supports findings that head injury can compound PTSD, which almost one in five officers have, and exacerbate drinking as a coping strategy.
The study is the first of its kind, and came about when researchers saw there was no data on the relationship between brain injury in police officers and their mental health.
“We did a brief scoping exercise of the literature, and were fascinated to see there was no research on brain injury in police officers, particularly in connection with brain injury and adverse mental health,” says Nick Smith, graduate research assistant at the University of Exeter.
Williams and Smith were surprised how many officers reported having a brain injury, although they expected there to be a relationship between TBI and adverse mental health.
“We found that, when officers have a mild brain injury, where they were assaulted or in a car accident, they could have PTSD. When they have this with head injury it can be long lasting, and they can exacerbate each other,” says Williams.
“Despite being a relatively small group, the findings were robust enough to say head injury, in the mix with PTSD, depression and drinking to cope, might lead to negative long-term outcomes,” says Williams.
The findings, the researchers argue, highlights a need to tackle TBI and the consequences of post-concussion syndrome, which can cause irritably, poor concentration and memory issues.
The paper states that exploring TBI in the police could, identify a major factor contributing towards ongoing mental health difficulties in a population where, based on previous research, the implications of TBI should not be overlooked.’
“If it’s not properly treated, it could lead to greater absence from work, so it’s reasonable for police forces to pick up on these issues to mitigate risk of long term sickness,” says Williams.
“Otherwise, I can see it snowballing – chronic stresses increase over time and the weight of negative experiences become harder to carry.
“This leads us to think we need a better system in place to identify TBI, an alert system to allow people come back into operations or situations in a way that’s healthy so they’re not exposed to more risk,” Williams says.
In sports, for example, the protocol following a concussion is much clearer, Williams says, and helps to lower a player’s risk of having a second concussion while recovering from the first.
“England Rugby does a great job with concussion management protocols, they identify the problem then do something about it, ensuring people are in the right mindset to be doing a very demanding job,” Williams says.
Increased awareness of TBI in the police would be a natural progression from being aware of prisoners with TBIs, says Williams.
“I’ve worked in prisons looking at how common head injury is in people who end up in prison, and various police forces became interested in working with us in a trauma-informed manner, taking on a more broad view of the vulnerabilities of people they’re working with.
“But working from this perspective involves understanding trauma of people who provide services as well,” he says. “Sixty, 70 percent of the time, police are trying to manage and look after vulnerable people. It’s important to recognise how they can become vulnerable themselves.”
There needs to be a system and trauma-informed principles in place for police officers to manage their own vulnerability, Williams says – and he’s hopeful this will happen in the future.
“Initial conversations with forces indicate a healthy attitude towards trying to improve how can improve psychological wellbeing,” he says.
But this isn’t just up to forces themselves. It’s also important, Smith adds, to lessen divide between police and public.
“Police need help like us – it’s important to understand how trauma might affect them.”
Williams says police are often portrayed negatively in the media, and it’s important that the public is aware of why they make the decisions they make and the laws they have that could lead to them suffering trauma.
PTSD, he says, is more likely to occur when officers don’t feel like society is backing them and the public doesn’t understand why they do what they do.
“It’s important for police to be understood as operating as people for people,” Williams says.
This will also require efforts from across probation, healthcare and education, Williams says, to better understand people from different backgrounds and how to build up empathy across society and reduce violence, as well as educating on the importance of identifying brain injuries when they occur.
Ultimately, Williams is hopeful that police forces want to give officers better protection from the consequences of TBI.
“Police officers need to think about myriad factors at same time, and we want them to be optimum capacity to do that,” Williams says.
This study was a pilot, and Smith hopes to do a much larger study in other police forces across the UK that controls for PTSD and depression to see if increases in post-concussion syndrome are due to head injury and not any other factors.
The first step, Smith says, is finding out the rate of TBI in the police force, then developing a tool to measure and monitor brain injury over time. The research, he says, will be done to help rehabilitate people with TBI, with the aim to help police understand the people they’re meeting, and vice versa.
Williams argues that this work is very relevant to public protection, and it’s important it continues.
How two community services are making tentative steps to normality
As pandemic restrictions lift, brain injury services are starting to come back out of hibernation. Jessica Brown speaks to two Headway groups across the country to see how they’re resuming support offline.
In Portsmouth, the local Headway has had a difficult time in recent months. Two service users have died from Covid-19, and another has been sectioned and taken to a secure facility after their mental health took a downturn.
There’s been a huge spike in mental health problems, and a few service users, who wouldn’t have done so under normal circumstances, have got in trouble with the police.
Most service users are gradually building their contact with the outside world again, with Headway’s help.
When lockdown began in March, service manager Deborah Robinson decided the best course of action was to identify the most vulnerable users and make sure she and her team maintained regular contact with them. The next challenge was gradually exposing them to more contact as restrictions began to ease.
“We regard it as a graduation – first is phone contact, then sitting in the garden with them, then inviting them on a walk once they’ve got confident enough to come out of their homes with us, then eventually we’ll suggest they come to a session with the group,” she says.
“Some people are too frail or anxious, so they won’t come out,” she says, “So we’ll have to carry on popping in to see them.”
This approach has proven particularly helpful in some ways, Robinson says. Before the virus, staff members hoped service users would speak up in sessions when they had a problem, but visiting people at home has allowed staff and volunteers to pick up on issues faster and get to know them better.
“One staff member met a service user in his garden, and noticed that the recycling bin was overflowing with alcohol. We knew he’d been a drinker in the past, so the staff member talked to him about his drinking, teasing information out,” Robinson says.
“He said he was drinking a lot, so we’ve been able to put in place goals to help him cut down on his drinking and put him in touch with AA, as well as various other things to help with a problem that reared its head in lockdown.”
Employees and volunteers, she adds, are also getting better at texting group members and touching base.
“It’s a mix of phoning people regularly and picking up the ones where there are issues. We’re getting more adept at that because it wasn’t something we did, and we’ve also picked up almost everyone’s carers because we’ve been talking to them to hear their concerns, too.”
Forty miles west in Salisbury, Headway arranged Zoom groups every week, but recognised that this option wasn’t suited to everyone.
“We were conscious to get actual face-to-face contact again, so as the guidelines have changed, we’ve thought about how we can work with that,” says Sarah Allen, service manager.
In recent weeks, online groups have continued, but staff members have started arranging small group meet-ups in various locations, including the outdoor café at Salisbury Museum, which Allen says provided a good learning opportunity.
One of Robinson’s major concerns in Portsmouth is how service users will react when they see other people not wearing masks or standing too close, and are told they have to adhere to guidelines themselves.
Allen, however, hopes meeting up in public places will help service users slowly accustom to these new ways of life.
“Some people coming to the groups haven’t been outside during the pandemic because all their activities have stopped, so it’s really important to model social distancing and hygiene behaviours,” Allen says.
“Somewhere like an outdoor café has been really useful because it’s about giving group members social contact in a setting where they can see people all around them modelling social distancing, staff wearing face masks and putting on hand sanitiser,” she says. “Then, when group members do go out and about more, it’ll be more familiar for them.”
In recent weeks, groups in Salisbury have also met up in a park, where they were able to socially distance.
Allen says coming out of lockdown and resuming services has been a learning curve for her, and she is realising that it’s sometimes more beneficial to have smaller groups than the maximum allowed by government guidelines.
She knows she will have to continue to adapt in unknown ways as government guidelines change.
But the future remains uncertain. Headway Salisbury doesn’t have its own centre, so rents community rooms to host sessions instead – and none have reopened yet. Allen plans on continuing outdoor activities for as long as possible, but is uncertain of what will happen as temperatures cool.
“Going into autumn and winter poses a new challenge,” she says. “I’m not sure how we’re going to meet if the government guidelines if the maximum number of people who can meet indoors stays the same,” she says.
Meanwhile in Portsmouth, premises have been locked up for the duration of lockdown. Robinson has seen an increase in demand for services, so as things resume back to pre-Covid 19, she says here’s a lot of thinking to be done about how the service is going to expand to accommodate increased need. She anticipates the service will need to expand by a third.
Both Portsmouth and Salisbury Headway services adapted quickly when the lockdown came in March. Adapting back to how things were before looks like it will be a longer, more difficult path – but while Allen and Robinson have faced slightly different challenges over the last few months, there’s no doubt they’ve both found silver linings in the challenges thrown at them so far.
The family experience of brain injury
After a person acquires a brain injury, the impact on the whole family can often be life changing as they adjust to a new reality and relationships come under intense pressure…
Karen Ledger (KL): When brain injury occurs, it’s like a bomb going off in the family. Life will never be the same again for any of the members of that family.
People will be shocked, bewildered and overwhelmed, and they then have to go through a complicated process of adjustment, and people reach that adjustment at different stages.
The person with the brain injury will generally have a neuropsychologist assigned to support them. Most will pay attention to people’s feelings and emotions, but the rest of the family may not have any psychological support.
This situation doesn’t get better of itself without professional input, it can get worse and people’s mental health can and often does spiral down.
Louise Jenkins (LJ): It’s a particular challenge if you’ve got someone with little or no insight. They often won’t recognise the need for or be willing to engage with neuropsychological treatment until much further down the line, by which stage, the family may have entered a more advanced stage of crisis and their whole family unit may be at risk of breakdown. There are complex emotions involved in the adjustment process following trauma which include shock, guilt and loss.
KL: That’s a scenario we see a lot. The client’s relationships may get to an advanced stage of deterioration and as Louise says, crisis, before they’re able to accept help. This is often because there is an immense amount to absorb from their new world of injury, rehabilitation and the medico-legal process and clients do not have the psychological space to consider how they are, never mind undertake the rehabilitation.
LJ: That’s where some of the challenges come in from the legal perspective. The compensation claim process is quite rigid in that generally speaking, only the injured person can claim for financial losses and for professional support, but we maintain that as the underpinning principle for compensation claims is to restore someone to their former lifestyle, you have to consider them both as an individual and as part of the family unit. We try to build into the claim some therapy sessions not only for the injured person but also for their spouse and their children.
Some defendants (compensators) say they’re happy to support that because, if the family unit breaks down and the uninjured spouse has been providing a lot of the day-to-day support, prompting and encouragement that the injured person needs, the cost of commercial care to replace that support is significantly more expensive than the amounts you can recover in a claim for support provided by a family member. It is also about embracing the spirit of the Rehabilitation Code and Serious Injury Guide in looking at the wider family need.
KL: Often, people can’t work anymore; they feel their work is taken away from them. People get their sense of identity out of work, as well as from being a spouse or a partner, a father or a mother. And if they lose their ability to earn and their relationships start to deteriorate these are often perceived as more failure and thereby serve to reduce a client’s confidence and self-worth.
LJ: It is akin to a bereavement process for the uninjured partner, yet the person is still there with you.
KL: People don’t have to have a death to experience loss, and loss can activate a bereavement process. So they’re grieving for the person they once knew, and now they’ve got this new person which makes adjustment to the injury complicated. And the thing about brain injuries is they’re hidden. The person looks the same but behaves differently to how they did before. It understandably takes a long time for clients and family members to really grasp the effects of brain injury, because they’re often traumatised, angry, discombobulated and distressed.
The family that includes somebody with a brain injury goes through a process of understanding, just as the client hopefully does. It’s a complex situation trying to comprehend what a brain injury means whilst feeling bereaved.
Family and children’s therapy is relevant too. Children often get missed because they deal with loss and trauma in different ways to adults. Children tend to get on with their lives, as if it’s not happening, so they need particular attention. They won’t be talking about it so much, but they’ll be experiencing it. The sooner that’s managed by specialists, the better it will be for children in the longer term, giving children the best chance of allowing normal development to take place.
LJ: It’s difficult because there’s a significant investment of time and energy put into implementing a rehabilitation programme and support around the injured person. This is integral to the claims process. The spouse can feel as if all the focus is on the injured person and they’ve been left out.
From a legal perspective, we try to involve the uninjured spouse as much as possible in discussing what we’re doing and why we’re doing it. We try to weave in that therapy support for the uninjured spouse so they come along the journey with us rather than becoming a disrupter to the rehabilitation programme because they feel excluded and unsupported. If securing interim payments through the claim to fund support is challenging at an early stage, our in-house team of client liaison managers, all of whom have a healthcare background, can provide time and input in discussing the challenges and in signposting for support both for the uninjured spouse and children as well as for the injured client. There are some really valuable resources for children, for example, which explain some of the problems that can arise in a parent who has sustained a brain injury to help them to understand and come to terms with changes in the family dynamics.
KL: People affected by brain injury can feel deserted by their partner and like a single parent. This is because they’ve lost their partner’s contribution to childcare and work in the home. The complexity and challenges of living in these circumstances should never be underestimated.
LJ: At the point of injury, they are in shock and just want to be there for the person who’s injured. I’ve worked with a number of people where the grief and adjustment process is very substantially delayed. These delays extend to weeks, months or even years.
They’re in a fight/flight/freeze situation. They’re managing a situation that’s about life and death initially in the most serious cases. When the acute stage is over and they have some space to start thinking about themselves, rather than the person who’s injured, they can start reflecting. It’s an emerging awareness that it’s never going to be the same again, that some degree of permanence will remain with the injuries, that this is how it will be in the longer term and a realisation that you need support to adjust to the new normal.
KL: It takes a while for that realisation to come in. I am often working with partners who are in that process of adjustment and what initially attracted them to the person pre-injury has been lost post injury, for example agile thinking and intelligence. Moreover they now find themselves in a caring role and one where many strangers are entering their home and talking to them in alien language! It’s not surprising that for many people this is often too challenging for them to manage and why therapy is needed as soon as possible for clients to regain their own personal power as soon as possible. They will have a private listening, respectful and tender place for them when the rest of their lives are so exposed.
LJ: They don’t know where that injured person is going to land with their recovery in the longer term. There’s a natural recovery process of a minimum of two years following brain injury, often longer, and they don’t know how much recovery the person’s going to make. They’re living with that uncertainty for a long time before being able to understand and adjust to what the long term will look like, often with significant physical, cognitive and behavioural changes which place great strain on sustaining relationships. Independent family law and financial advice is often essential to protect both parties in the event that the relationship does break down.
KL: I believe that acquired head injury is usually devastating to the person and those around them. However, in my experience, people are often amazing in how they find the strength to establish new ways of being and making their life work for them. Therapy can often speed up that process because clients feel heard, respected and understood, a powerful combination for a restorative process particularly when they are so often feeling powerless. This process can help families stay together or decide to go their separate ways and with support they are more likely to do this without acrimony and additional trauma. Observing and supporting clients and their loved ones to dig deep to find the strength and commitment to establish a new life is such an amazing privilege and honour for me.
LJ : When the claims process is managed by expert serious injury lawyers, early access to specialist rehabilitation and support will enable an injured claimant to restore their life to the best possible position and allow them to maximise their potential for the long term, restoring a sense of control and positivity for the future. Working together with therapists like Karen is essential to ensure that a multi-disciplinary network of support can be put in place in order to support an injured person to achieve their goals and rebuild their life as an individual and as part of a family unit after a life changing injury.
Louise Jenkins is a partner at Irwin Mitchell and leads the serious injury team at the firm’s Sheffield office. Karen Ledger is managing director of KSL Consulting and a therapist, counsellor and supervisor with over 30 years of experience.
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