UAB researchers unlock mystery of memory loss in epilepsy patients

New research from the University of Alabama at Birmingham identifies an epigenetic cause for why patients with temporal lobe epilepsy tend to have memory loss, and suggests a potential way to reverse that loss. The findings, published in April in the Annals of Translational and Clinical Neurology, indicate the discovery may have implications for many other memory disorders.

Patients with temporal lobe epilepsy have a high incidence of memory loss, even when seizures associated with epilepsy are controlled well by medication. The UAB research team targeted the BDNF gene, which is known to play a role in memory formation. The gene produces a protein called brain-derived neurotrophic factor.

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Funding for the study came from the National Institute of Mental Health, the UAB Intellectual and Developmental Disabilities Research Center, the Epilepsy Foundation, the Civitan International Research Foundation, and the Evelyn F. McKnight Brain Research Foundation.

Breakdown of Baymax’s neurological scan of Hiro in Big Hero Six

Getting the chance to see Big Hero Six for a second time, on my computer, allowed me to pause the screen and check out all the cool details more carefully.  I was especially interested in the scene where Baymax is scanning Hiro’s neurological functioning.  I wanted to see if the writers and animators just phoned this bit in with a bunch of made-up jargon and figures, or if they actually did their research to add an extra level of authenticity.  I was happy to find that it was the later of these two options.  Even more so than I had hoped for.  They didn’t just do the research, they clearly got a real neurologist to consult on this…  It’s a super impressive facsimile of what a real, super high-tech neuro-scan would look like, right down to being gender and age-specific.

Check it out:

On the viewer’s left side of the screen, just below ‘diagnosis’ there is a list of symptoms.  After ‘no physical injury’ it reads ‘GPR54 detected.’ GPR54, also known as the ‘Kisspeptin receptor’ mitigates endocrine functioning during puberty.  Its activation causes the release of gonadotropin hormones.  In short, it is the mechanism that ‘turns on’ the gonads and basically readies the body for sexual procreation.  All of the aches and pains and weird feelings that occur during puberty are a result of the body adjusting to changes in the gonadal system.   The Kisspeptin receptor usually becomes active around age 11 in girls and 12 in boys.  Hiro is 14, which suggests he’s a bit of a late-bloomer in regards to his physical development, but this is not especially uncommon among children who are intellectually precocious.  No one really knows why this is; it’s just a common correlational finding.  

Next it reads ‘High levels of GnRH.’  GnRH is short for gonadotropin-releasing hormone.  This is a peptide hormone that regulates the release of additional hormones in the anterior pituitary gland within the hypothalamus.  These hormones are released in pulses or waves and it’s often different between boys and girls.  In girls, the pulses tend to occur at a varied rate throughout the menstrual cycle, with big surges occurring just prior to ovulation.  In boys, meanwhile, GnRH is secreted in pulses at a more constant frequency.  Detection of high levels of GnRH in Hiro indicates a pulse of the hormone is occurring and his gonads are in a state of spermatogenesis (i.e. his body is creating sperm… which is likely much more information than anyone needs regarding a cartoon character). 

After that it reads ‘increased pituitary activity.’  Again, the pituitary gland is the main generator for these hormones.  Electrical activity generating in the pituitary causes the release of various hormones.  The pituitary is involved in all manner of state and trait-based functioning.  In this case, the heightened activity is most likely connected to the pulse of GnRH. 

Next it reads ‘High Testosterone.’ Testosterone is an androgen steroid hormone secreted in the testicles of males and the ovaries of females.  Higher levels of testosterone during physical development aids in the tissue growth of secondary sexual characteristics, as well as augmenting muscle and bone mass, and the growth of body hair.  Secretion of testosterone from the adrenal glands is also associated with stress, helping to ready muscles tension and blood flow in so-called ‘fight-or-flight’ situations.  Heightened testosterone in Hiro just means that his body is going through the process of puberty; that his body is at an accelerated process of physical development (i.e. a ‘growth spurt’). 

Next, it reads ‘vocal fluctuation,’ which is pretty straightforward.   During puberty, the larynx grows and expands at a fast pace, altering the pitch and vibration of vocal folds.  Similar to GnRH, the hormones that aid in the growth of the larynx also occur in surges or pulses and this is why adolescent voices sometimes seem to ‘crack’ or suddenly fluctuate. 

Finally, it the readout reads ‘emotional instability.’  This is a complex one.  Obviously, a significant portion of Hiro’s emotional issues is related to his morning over his brother’s death.  Nevertheless, emotional instability is highly common during the process of puberty, a byproduct of hormonal fluctuations as well as differential activity in the brain.  Up in the picture, on the viewer’s right side, there are two side-views of Hiro’s brain.  The first is a baseline image, the picture Baymax took when he first met Hiro.  The second is a current image.  These are both imitations of what full side-view brain scans look like on a functional MRI (magnetic resonance imaging). 

Hiro’s baseline shows relatively normative brain activity, with electrical activity occurring in a broad, spectral fashion.  In the second image, however, the electrical activity is more focal, concentrating in the lower mid-brain region.  This is where the hypothalamus is, and the concentrated activity indicates that the pituitary is in the process of triggering the release of all manner of hormones. 

Structurally, the hypothalamus resides right next to the amygdala, part of the limbic system, and a primary component to emotion.  The amygdala is believed to be the part of the brain that connects thoughts and memories to physical sensations.  Put simply, it is what creates emotion.  Being situated so closely to the hypothalamus, an increase in limbic system activity may be merely a byproduct of increases of growth-related hormones during adolescence.  And this often contributes to greater emotional instability tied in with growth spurts. 

Furthermore, the increased activity in the midbrain region often acts to reduce activity in other areas, especially the frontal lobes.  The frontal lobes are the area of the brain most associated with decision-making, foresight, and judgment.  Apparently, there is only so much electrical activity that can occur in the brain at any given moment.  And a concentration of activity in the lower regions can actually reduce such activity in the upper regions.  So, when an adolescent makes a rash decision, acts out, or shows poor judgment, it may often be a result of reduced activity in frontal lobes that occur as a result of heightened activity elsewhere.  And we see this actually occur later on in the movie when Hiro makes a very rash decision and tries to get Baymax to kill Professor Callaghan.  Not only is Hiro still morning Tadashi and feels extremely betrayed by Professor Callaghan, but he’s also at a stage of development where his frontal lobes are at a lower-than-average level of activity… which can lead to rash, impulsive decision-making.  Fortunately, Gogo, Honey and the gang are there to stop Baymax and prevent Hiro from a decision he would ultimately regret.

Finally, the readout also shows Hiro’s heart rate and body temperature, both of which are in the normative range. 

Below the brain scans on the right-hand side is a list of abbreviations of hormones and neurotransmitters.   First is GnRH (or gonadotropin-releasing hormone) already covered above.  Next is LH, which stands for luteinizing hormone.  For girls, luteinizing hormones supports ovarian theca cells in later stages of the menstrual cycle.  In boys, luteinizing hormones helps to activate leydig cells in the testis, assisting in the production of testosterone. 

After that is a figure for FSH.  FSH stands for follicle-stimulating hormone.  FSH is a specific type of luteinizing hormone that activates pubertal maturation.  In girls, FSH is crucial to determining which egg is selected in ovulation.  FSH seems to be able to determine which egg follicle is the strongest and most ready for ovulation (i.e. which egg has the greatest chase of being fertilized and growing into a healthy baby).  In boys, FSH induces sertoli cells to secrete androgen-binding proteins… it helps to activate cells associated with male sexual development. 

Next is T, also known as T3 or Triiodothyronine.   This is a thyroid hormone that plays a significant role in multiple areas of bodily functioning, including metabolism, body temperature, and heart rate.  Elevated levels of T3 is a critical component to adolescent development.  It helps navigate metabolism so to give growing regions the extra energy needed for cellular generation (tissue growth).  For his size and weight, Hiro’s T3 level of 170 definitely suggests he is going through a growth spurt.   

Next is E2, which stands for estradiol.  Estradiol is both a steroid as well as a sex hormone.  It is the primary sex hormone in girls, helping to activate genes whose expression allows further development of the vagina as well as breast growth.  In boys, estradiol acts to help keep nascent sperm cells from dying off prematurely.  Significant heightened E2 levels in boys is a primary indicator of the genetic condition known as Klinefelters syndrome (also known as intersex or XYY syndrome).  At 22, Hiro’s E2 level is a touch high, but well within the normative range for a boy his age. 

And finally, there’s F, which totally perplexes me.  There’s no hormone I can think of that is abbreviated as F. So what’s Hormone F?  I’m still not sure and my best guess is that it’s an in-joke for fans of the anime, Dragonball Z.  

So all of this, this entire business that took me half an hour to write, is detailed in a single scene that lasts maybe ten seconds.  It’s really impressive the amount of detail and research that went into this one scene. 

Positives of BPD

(Borderline personality disorder/emotional regulation disorder).
I made a post like this a while ago when I first started to use tumblr. It was pretty brief and choppily written (in my opinion) so as I’ve said, I decided to remake this with more explanation/research included for more understanding and since lots found it and really liked it. Might as well start 2015 off focusing on these positives.

This is important for awareness/understanding and for those of you who have it as it really helped me overcome feelings of guilt towards having BPD/ERD and the horrible stigma. It helped me gain self-acceptance. That is why I decided to share it here.

Emotional Regulation Disorder (BPD) is a chronic mental disorder of emotional hypersensitivity and dysregulation- meaning reactions are hypersensitive/fire off erratically (seizure-like) and do not regulate or process well and the same as others. This causes people with the condition to easily react to other stimuli that other people don’t, become easily triggered and lack the ability to regulate the extremities. It affects thought processes/patterns, emotions, behavior, beliefs, and other forms of functioning. The limbic system plays a crucial role in these reactions, as it affects memory, emotional reactions, learning and developmental ability, thought pattern, behavior, and the way the body perceives external stimuli. Clearly, it then causes a wide range of symptoms (depressive, dissociative, hallucinations, delusions, anger, suicidal ideations, etc) as there are hundreds of ways to recognize ERD/BPD reactions, symptoms, and traits/characteristics. ERD/BPD reactions are “full systematic responses.” As the condition influences ‘all’ emotional reactions and other functioning, and there is such a wide range of symptoms, it is often described as a version of multiple mental disorders combined. (borderline of multiple conditions)
However, these reactions mean the hypersensitivity and dysregulation can affect positive reactions as well. Specifically, with research, analysis, and observations, some hallmark traits/characteristics may be:

-Passionate:  As the level of psychological reactions highly differ in those with BPD compared to those without, individuals with the condition experience the ‘extremity’ of emotions/responses. The research on the psychological reactions on those without the condition compared to those with it, for instance, includes: Sadness-depression/grief, embarrassment-humiliation, nervousness-panic, anger-rage, and happiness-euphoria/passion, to name a few. Individuals with BPD have been observed to be especially very passionate and reactive as they often react and express this passion and euphoria.

-Insightful: Studies on BPD indicated that because of their own hypersensitivity and pain, people with BPD may easily connect to what is around them. For instance, they were able to easily read facial expressions, behavior, and emotions of those around them in an expression test. People with BPD may take experiences like these and emotions and turn it into insight and understanding, for one example, and have been shown to have an unusually high level of insight.

-Curious: Observations and studies show unusually high curiosity is common in some people with BPD from this high connection with their senses and surroundings, “sort of like a child. People with BPD are often described as having ‘childlike’ traits and characteristics referring to the interests, energy, innocence, and confusion from the unregulated emotions and reactions.”

-Compassionate/sympathetic: Again, as a result of their own hypersensitivity and pain, many with BPD may portray a high level of sympathy and understanding to others and the things around them.

-Loving/appreciative: Idealization is a main characteristic of BPD. People with BPD may idealize and glorify another individual in their life because of such strong emotions and needs, and they may be very appreciative because of hypersensitivity and painful experiences.

-Dependent: Dependency is often a hallmark symptom of BPD. One main reason for this is the extremity of the hypersensitive emotions often generating a huge fear of being alone and abandonment far more than most can imagine. Identity symptoms, such as a lack of sense of self, may also result in dependency. Dependency can be a good thing with the proper balance, like support, closeness, affection, and interconnectivity.

-Protective: Research indicates this trait is more pronounced in ‘male’ individuals with bpd, or people with (higher testosterone levels), although not restricted. This reaction may be common as a result of the intensity someone with BPD feels towards a situation or person and have been shown it may relate to the high aggression noted in BPD symptoms.

-Loyal/caring: Related to the last few, the strong reactions may often relate and connect to loyalty and care.

-Creative: An unusually high amount of writers have BPD. High levels of creativity were linked to some individuals with BPD in research cases- new ideas, artistic or musical ability, writing, or multiple other areas of creativity. Fantasizing is a common characteristic in BPD as well as daydreaming- a low, normal level of dissociation.

-High nociception (pain tolerance): Studies indicate alterations between pain processing in over half of those with BPD as opposed to individuals without. Studies show alterations in acute pain processing- they have a higher tolerance for such. Individuals with BPD were far more likely to tolerate it, despite being hypersensitive psychologically. The result of this comes from different systematic responses and antinociception and may be a result of long-term self harm behavior in some cases.

-High awareness/connection: Again, as a result of being easily connected to surroundings and outside stimuli, people with BPD have been observed have high awareness. Marsha Linehan also states they may have more levels of spiritual experiences more often. Furthermore, people with BPD have been observed to have a high level of comfort, security, and connection to nature and animals, such as pets, as stated by the DSM.

-Discipline: Obsessive compulsive features are quite common in BPD- intrusive thoughts in the thought pattern/processes, repetitive behavior as a result of self harm, paranoia, distress, etc, and repetitive speech, to name a few. Research observes people with BPD to also display high levels of self-discipline, work orientation, and drive connected to the repetitive processing.

-Alluring/Interesting: Because of the intensity, many people note in observation the interesting and/or alluring behavior or energy of someone with BPD. Furthermore, people with BPD are sometimes referred to as a “siren” in psychology as a result. Other studies have stated foundings of “physical attractiveness” patterns-however, realistically, it’s not “possible” for a neurological disorder to be related to any sort of physical attractiveness unless they were simply just attractive people or if portrayal plays a part.

-Individualistic/engaging: Many in observations and studies claimed to notice the extreme individualism and/or depth and mysterious/engaging behavior/feelings given off from BPD individuals as a result of the connection, hypersensitivity, and reactions.

-Sarcastic/funny: The DSM and multiple other sources /observations state some people with BPD may often express sarcasm and humor.

-Bold: One of the main symptoms of BPD is impulsiveness; however, research states this may be tied to a positive trait in some individuals with BPD- boldness, bravery, and ability to speak their mind.

-Strong: On a psychological level, people with BPD are often described as feeling the most intense, agonizing reactions, and one needs to be quite strong to handle them.

-Lively: Intense reactions may result in high euphoria and engaging/active behavior and energy.

-Intense- Many state in observations and research the intensity of the reactions and energy from someone with BPD from all these ^ reactions.

Marsha Linehan
states, “Although it is likely that emotion dysregulation is most pronounced in negative emotions, borderline individuals also seem to have difficulty regulating positive emotions and their sequelae.”

Corpus callosum.

The corpus callosum is a wide, flat bundle of neural fibers beneath the cortex and it connects the left and right cerebral hemispheres, allowing interhemispheric communication. It is the largest white matter structure in the brain.

Clinical conditions related to corpus callosum activity: 

  • Epilepsy: the symptoms of refractory epilepsy can be reduced by cutting the corpus callosum in an operation known as a corpus callosotomy. This is usually reserved for cases in which complex or grand mal seizures are produced by an epileptogenic focus on one side of the brain, causing an interhemispheric electrical storm. The work up for this procedure involves an electroencephalogram, MRI, PET scan, and evaluation by a specialized neurologist, neurosurgeon, psychiatrist, and neuroradiologist before surgery can be considered.
  • Other diseases: Anterior corpus callosum lesions may result in akinetic mutism or tactile anomia. Posterior corpus callosum (splenium) lesions may result in alexia (inability to read) without agraphia. Also: alien hand syndrome; agenesis of the corpus callosum (dysgenesis, hypogenesis, hypoplasia); malformations of the corpus callosum; septo-optic dysplasia (deMorsier syndrome); multiple sclerosis with the symptom Dawson’s fingers; mild encephalopathy with a reversible splenial lesion, a rare encephalopathy (or encephalitis) of unknown origin with a transient lesion in the posterior part of the corpus callosum, mostly associated with infectious diseases.

(Picture by Neurons want food).

How Stephen Hawking, diagnosed with ALS decades ago, is still alive

On April 20, 2009, a moment arrived that doctors had foretold for decades. Stephen Hawking, a scientist who overcame debilitating disease to become the world’s most renowned living physicist, was on the cusp of death. The University of Cambridge released grim prognoses. Hawking, diagnosed with amyotrophic lateral sclerosis (ALS) at the age of 21, was described as “very ill” and “undergoing tests” at the hospital. Newspapers ran obituary-esque articles. It seemed time was up for the man who so eloquently explained it.

But, as is his custom, Hawking survived.

Hawking shouldn’t be able to do the things he now does. The 73-year-old shouldn’t be able to deliver meditations on the existence of God. He shouldn’t be able to fret over artificial intelligence or humanity’s capacity for self-destruction. And he most definitely shouldn’t be able to attend the BAFTAs — Britain’s academy awards — settled inside the wheelchair that has carried him for decades, expressing admiration for a recent biopic that paid homage to his struggle. But yet, he is. And he does.

It’s difficult to overstate the lethality of ALS, the condition with which Hawking lives. The disorder can befall anyone. It first brings muscle weakness, then wasting, then paralysis, ripping away the ability to speak and swallow and even breathe. The ALS Association says the average lifespan of someone diagnosed with the condition is between two and five years. More than 50 percent make it past year three. Twenty percent make it past year five. From there, the number plummets. Less than 5 percent make it past two decades.

And then there’s Hawking. He has passed that two-decade mark twice — first in 1983, then in 2003. It’s now 2015. His capacity for survival is so great some experts say he can’t possibly suffer from ALS given the ease with which the disease traditionally dispatches victims. And others say they’ve simply never seen anyone like Hawking.

It’s difficult to overstate the lethality of ALS, the condition with which Hawking lives. The disorder can befall anyone. It first brings muscle weakness, then wasting, then paralysis, ripping away the ability to speak and swallow and even breathe. The ALS Association says the average lifespan of someone diagnosed with the condition is between two and five years. More than 50 percent make it past year three. Twenty percent make it past year five. From there, the number plummets. Less than 5 percent make it past two decades.

And then there’s Hawking. He has passed that two-decade mark twice — first in 1983, then in 2003. It’s now 2015. His capacity for survival is so great some experts say he can’t possibly suffer from ALS given the ease with which the disease traditionally dispatches victims. And others say they’ve simply never seen anyone like Hawking.

“He is exceptional,” Nigel Leigh, a professor of clinical neurology at King’s College London, told the British Medical Journal in 2002. “I am not aware of anyone else who has survived with [ALS] as long. What is unusual is not only the length of time, but that the disease seems to have burnt out. He appears to be relatively stable. … This kind of stabilization is extremely rare.”

This description is not in any way unusual. More than a decade later, when Hawking turned 70 in 2012, more researchers were baffled and amazed. Anmar al-Chalabi of King’s College London told the Associated Press Hawking was “extraordinary. … I don’t know of anyone who’s survived this long.”

So what makes Hawking different from the rest? Just luck? Or has the transcendent nature of his intellect somehow stalled what seemed an imminent fate? No one’s quite sure. Even Hawking himself, who can expound at length on the mechanics that govern the universe, is circumspect when it comes to an accomplishment that rivals his academic triumphs. “Maybe my variety [of ALS] is due to bad absorption of vitamins,” he said.

Hawking’s battle with ALS was different from the beginning. And those differences, scientists say, partly explain his miraculous longevity. The onset of ALS normally occurs later in life — the average age of diagnosis is 55 — but Hawking’s symptoms materialized when he was very young. It began with a stumble.

“In my third year at Oxford, I noticed that I seemed to be getting more clumsy, and I fell over once or twice for no apparent reason,” Hawking once wrote. “But it was not until I was at Cambridge that my father noticed, and took me to the family doctor. He referred me to a specialist, and shortly after my 21st birthday, I went into hospitals for tests. … It was a great shock to me to discover that I had motor neuron disease,” the name for the group of progressive neurological disorders that includes ALS.

Though the early diagnosis resigned him to a life of sickness, it also granted him a chance at surviving the disease longer than those who are diagnosed much later. “We have found that the survival in younger patients is strikingly better and is measured in many years — in some cases more than 10,” Leigh told the British Medical Journal. “… It’s a different beast if you start young, oddly, and no one knows why.”

Leo McCluskey of the University of Pennsylvania told Scientific American that ALS primarily kills in two different ways. One affects the breathing muscles. “So the common way people die is of respiratory failure,” he said. The other is the failure of swallowing muscles, which can result in dehydration and malnutrition. “If you don’t have these two things, you could potentially live for a long time,” he said.

But as long as Hawking has lived? For his part, Hawking says his work, focused through his disability, granted him years that wouldn’t have been available to others. Someone in a more physical field — like, say, Lou Gehrig, the New York Yankee who contracted ALS in his 30s — couldn’t have functioned at so high a level. “It has certainly helped that I have a job and that I have been looked after so well,” Hawking told the New York Times in 2011. “I am lucky to be working in theoretical physics, one of the few areas in which disability is not a serious handicap.”

If anything, Hawking illustrates the very different ways ALS can afflict its victims — “just an incredible, incredible example,” McCluskey said.

It has also given rise to one of the most striking contrasts of pop science. There is Stephen Hawking’s atrophied frame, slack-jawed expression and slumped shoulders. And there is Hawking’s unmatched mind, inhabiting the stars.

Scientists have converted human skin cells into brain cells

A number of current medical treatments involve a process in which one type of human cell is converted to another, such as stem cells being converted to skin cells. During this process, there’s a stage called the stem cell stage, where the original cells are at risk of converting into multiple types of cells, rather than the single, desired type. But now a team of scientists from Washington University in the US has figured out how to avoid the stem cell stage altogether, and have successfully converted skin cells directly into functioning brain cells.

The team produced a specific type of brain cell called a medium spiny neuron. These nerve cells are important for controlling movement of the body and are the main cell type affected inHuntington’s disease.

The findings, which are published in the journal Neuron, report that the cells were implanted in the brains of mice, and survived for at least six months.

“Not only did these transplanted cells survive in the mouse brain, they showed functional properties similar to those of native cells,” said developmental biologist and lead author of the study, Andrew S. Yoo, in a press release. "These cells are known to extend projections into certain brain regions. And we found the human transplanted cells also connected to these distant targets in the mouse brain. That’s a landmark point about this paper.“

The team grew the human skin cells in an environment that resembled that of brain cells. Next they exposed the cultured cells to two microRNAs - small non-coding molecules - that unravelled the DNA needed for brain cells. The next hurdle was to reprogram the cells into specific medium spiny neurons, and this was done by exposing them to transcription factors - molecules that control the activity of a gene.

The team is now reprogramming cells taken from patients with Huntington’s disease into medium spiny neurons, using this method. 

This new approach presents the possibility of using a patient’s own cells in regenerative medicine, drastically reducing the risk of the cells being rejected by the immune system.

Source: EurekAlert

2

“The smell of a walk”.

A man who was completely paralysed from the waist down can walk again after a British-funded surgical breakthrough which offers hope to millions of people who are disabled by spinal cord injuries.

Polish surgeons used nerve-supporting cells from the nose of Darek Fidyka, a Bulgarian man who was injured four years ago, to provide pathways along which the broken tissue was able to grow. The 38-year-old, who is believed to be the first person in the world to recover from complete severing of the spinal nerves, can now walk with a frame and has been able to resume an independent life, even to the extent of driving a car, while sensation has returned to his lower limbs.

The cells from the patient’s olfactory bulb in the brain were removed and grown in the lab. The olfactory bulb is on the inferior side of the brain and it transmits smell information from the nose to the brain, and is thus necessary for a proper sense of smell. The olfactory bulb is, with the subventricular zone, one of only two structures in the brain observed to undergo continuing neurogenesis in adult mammals. In most mammals, new neurons are born from neural stem cells in the sub-ventricular zone and migrate rostrally towards the main and accessory olfactory bulbs. 

The cells taken from the nasal cavity were injected into the spinal cord above and below the damaged site and strips of nerve fibres were taken from the patient’s ankle to form a bridge for the cells to grow across.

Professor Geoffrey Raisman, whose team at University College London’s institute of neurology discovered the technique, said: “We believe that this procedure is the breakthrough which, as it is further developed, will result in a historic change in the currently hopeless outlook for people disabled by spinal cord injury.” Raisman said he had never believed the “observed wisdom” that the central nervous system cannot regenerate damaged connections. He added: “Nerve fibres are trying to regenerate all the time. But there are two problems – crash barriers, which are scars, and a great big hole in the road. “In order for the nerve fibres to express that ability they’ve always had to repair themselves, first the scar has to be opened up, and then you have to provide a channel that will lead them where they need to go.”

He stressed that what had been achieved was a leap forward beyond promoting “plasticity” – the rewiring of remaining connections. The professor added: “The number of patients who are completely paralysed is enormous. There are millions of them in the world. “If we can convince the global neurosurgeon community that this works then it will develop very rapidly indeed.”

(To read more).

First human head transplant could happen in two years

IT’S heady stuff. The world’s first attempt to transplant a human head will be launched this year at a surgical conference in the US. The move is a call to arms to get interested parties together to work towards the surgery.

The idea was first proposed in 2013 by Sergio Canavero of the Turin Advanced Neuromodulation Group in Italy. He wants to use the surgery to extend the lives of people whose muscles and nerves have degenerated or whose organs are riddled with cancer. Now he claims the major hurdles, such as fusing the spinal cord and preventing the body’s immune system from rejecting the head, are surmountable, and the surgery could be ready as early as 2017.

Canavero plans to announce the project at the annual conference of the American Academy of Neurological and Orthopaedic Surgeons (AANOS) in Annapolis, Maryland, in June. Is society ready for such momentous surgery? And does the science even stand up?

The first successful head transplant, in which one head was replaced by another, was carried out in 1970. A team led by Robert White at Case Western Reserve University School of Medicine in Cleveland, Ohio, transplanted the head of one monkey onto the body of another. They didn’t attempt to join the spinal cords, though, so the monkey couldn’t move its body, but it was able to breathe with artificial assistance. The monkey lived for nine days until its immune system rejected the head. Although few head transplants have been carried out since, many of the surgical procedures involved have progressed. “I think we are now at a point when the technical aspects are all feasible,” says Canavero.

This month, he published a summary of the technique he believes will allow doctors to transplant a head onto a new body (Surgical Neurology International, doi.org/2c7). It involves cooling the recipient’s head and the donor body to extend the time their cells can survive without oxygen. The tissue around the neck is dissected and the major blood vessels are linked using tiny tubes, before the spinal cords of each person are cut. Cleanly severing the cords is key, says Canavero.

The recipient’s head is then moved onto the donor body and the two ends of the spinal cord – which resemble two densely packed bundles of spaghetti – are fused together. To achieve this, Canavero intends to flush the area with a chemical called polyethylene glycol, and follow up with several hours of injections of the same stuff. Just like hot water makes dry spaghetti stick together, polyethylene glycol encourages the fat in cell membranes to mesh.

Next, the muscles and blood supply would be sutured and the recipient kept in a coma for three or four weeks to prevent movement. Implanted electrodes would provide regular electrical stimulation to the spinal cord, because research suggests this can strengthen new nerve connections.

When the recipient wakes up, Canavero predicts they would be able to move and feel their face and would speak with the same voice. He says that physiotherapy would enable the person to walk within a year. Several people have already volunteered to get a new body, he says.

The trickiest part will be getting the spinal cords to fuse. Polyethylene glycol has been shown to prompt the growth of spinal cord nerves in animals, and Canavero intends to use brain-dead organ donors to test the technique. However, others are sceptical that this would be enough. “There is no evidence that the connectivity of cord and brain would lead to useful sentient or motor function following head transplantation,” says Richard Borgens, director of the Center for Paralysis Research at Purdue University in West Lafayette, Indiana.

If polyethylene glycol doesn’t work, there are other options Canavero could try. Injecting stem cells or olfactory ensheathing cells – self-regenerating cells that connect the lining of the nose to the brain – into the spinal cord, or creating a bridge over the spinal gap using stomach membranes have shown promise in helping people walk again after spinal injury. Although unproven, Canavero says the chemical approach is the simplest and least invasive.

But what about the prospect of the immune system rejecting the alien tissue? Robert White’s monkey died because its head was rejected by its new body. William Mathews, chairman of the AANOS, says he doesn’t think this would be a major problem today. He says that because we can use drugs to manage the acceptance of large amounts of tissue, such as a leg or a combined heart and lung transplant, the immune response to a head transplant should be manageable. “The system we have for preventing immune rejection and the principles behind it are well established.”

Keep reading

How Dogs Understand What We Say

Scientists — and anyone who lives with a canine — know that dogs pay close attention to the emotion in our voices. They listen for whether our tone is friendly or mean, how the pitch goes up or down and even the rhythms in our speech.

But what about the meaning of the words we say?

Sure, a few studies have reported on super smart dogs that know hundreds of words. And Chaser, a border collie in South Carolina, even learned 1,022 nouns and commands to go with them.

But otherwise, there’s little evidence that dogs differentiate between speech with meaningful words from sounds that contain only inflections, says neurobiologist Attila Andics, at the MTA-ELTE Comparative Ethology Research Group in Budapest.

“We know quite a bit about how much dogs get about how we say things, Andics says, "but we know quite little about how much dogs get about what we say to them.”

That’s about to change.

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Drugs that activate brain stem cells may reverse multiple sclerosis

Two drugs already on the market — an antifungal and a steroid — may potentially take on new roles as treatments for multiple sclerosis. According to a study published in Nature today, researchers discovered that these drugs may activate stem cells in the brain to stimulate myelin producing cells and repair white matter, which is damaged in multiple sclerosis. The study was partially funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

Specialized cells called oligodendrocytes lay down multiple layers of a fatty white substance known as myelin around axons, the long “wires” that connect brain cells. Myelin acts as an insulator and enables fast communication between brain cells. In multiple sclerosis there is breakdown of myelin and this deterioration leads to muscle weakness, numbness and problems with vision, coordination and balance.

“To replace damaged cells, the scientific field has focused on direct transplantation of stem cell-derived tissues for regenerative medicine, and that approach is likely to provide enormous benefit down the road. We asked if we could find a faster and less invasive approach by using drugs to activate native nervous system stem cells and direct them to form new myelin. Our ultimate goal was to enhance the body’s ability to repair itself,” said Paul J. Tesar, Ph.D., associate professor at Case Western Reserve School of Medicine in Cleveland, and senior author of the study.

It is unknown how myelin-producing cells are damaged, but research suggests they may be targeted by malfunctioning immune cells and that multiple sclerosis may start as an autoimmune disorder. Current therapies for multiple sclerosis include anti-inflammatory drugs, which help prevent the episodic relapses common in multiple sclerosis, but are less effective at preventing long-term disability. Scientists believe that therapies that promote myelin repair might improve neurologic disability in people with multiple sclerosis.    

Adult brains contain oligodendrocyte progenitor cells (OPCs), which are stem cells that generate myelin-producing cells. OPCs are found to multiply in the brains of multiple sclerosis patients as if to respond to myelin damage, but for unknown reasons they are not effective in restoring white matter. In the current study, Dr. Tesar wanted to see if drugs already approved for other uses were able to stimulate OPCs to increase myelination.  

OPCs have been difficult to isolate and study, but Dr. Tesar and his colleagues, in collaboration with Robert Miller, Ph.D., professor at George Washington University School of Medicine and Health Sciences in Washington, D.C., developed a novel method to investigate these cells in a petri dish. Using this technique, they were able to quickly test the effects of hundreds of drugs on the stem cells.

The compounds screened in this study were obtained from a drug library maintained by NIH’s National Center for Advancing Translational Sciences (NCATS). All are approved for use in humans. NCATS and Dr. Tesar have an ongoing collaboration and plan to expand the library of drugs screened against OPCs in the near future to identify other promising compounds.

Dr. Tesar’s team found that two compounds in particular, miconazole (an antifungal) and clobetasol (a steroid), stimulated mouse and human OPCs into generating myelin-producing cells.

Next, they examined whether the drugs, when injected into a mouse model of multiple sclerosis, could improve re-myelination. They found that both drugs were effective in activating OPCs to enhance myelination and reverse paralysis. As a result, almost all of the animals regained the use of their hind limbs. They also found that the drugs acted through two very different molecular mechanisms.

“The ability to activate white matter cells in the brain, as shown in this study, opens up an exciting new avenue of therapy development for myelin disorders such as multiple sclerosis,” said Ursula Utz, Ph.D., program director at the NINDS.

Dr. Tesar and his colleagues caution that more research is needed before miconazole and clobetasol can be tested in multiple sclerosis clinical trials. They are currently approved for use as creams or powders on the surfaces of the body but their safety administered in other forms, such as injections, in humans is unknown.

“Off-label use of the current forms of these drugs is more likely to increase other health concerns than alleviate multiple sclerosis symptoms. We are working tirelessly to ready a safe and effective drug for clinical use,” Dr. Tesar said.

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