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Traumatic brain injury (TBI) –– defined as a bump, blow or jolt to the head that disrupts normal brain function –– sent 2.5 million people in the U.S. to the emergency room in 2014, according to statistics from the U.S. Centers for Disease Control and Prevention. Today, researchers report a self-assembling peptide hydrogel that, when injected into the brains of rats with TBI, increased blood vessel regrowth and neuronal survival.
The researchers will present their results at the American Chemical Society (ACS) Fall 2019 National Meeting & Exposition. ACS, the world’s largest scientific society, is holding the meeting here through Thursday. It features more than 9,500 presentations on a wide range of science topics.
“When we think about traumatic brain injuries, we think of soldiers and athletes,” says Biplab Sarkar, Ph.D., who is presenting the work at the meeting. “But most TBIs actually happen when people fall or are involved in motor vehicle accidents. As the average age of the country continues to rise, the number of fall-related accidents in particular will also increase.”
TBIs encompass two types of injuries. Primary injury results from the initial mechanical damage to neurons and other cells in the brain, as well as blood vessels. Secondary injuries, which can occur seconds after the TBI and last for years, include oxidative stress, inflammation and disruption of the blood-brain barrier. “The secondary injury creates this neurotoxic environment that can lead to long-term cognitive effects,” Sarkar says. For example, TBI survivors can experience impaired motor control and an increased rate of depression, he says. Currently, there is no effective regenerative treatment for TBIs.
Sarkar and Vivek Kumar, Ph.D., the project’s principal investigator, wanted to develop a therapy that could help treat secondary injuries.
We wanted to be able to regrow new blood vessels in the area to restore oxygen exchange, which is reduced in patients with a TBI. Also, we wanted to create an environment where neurons can be supported and even thrive.”
Biplab Sarkar, Ph.D., New Jersey Institute of Technology
The researchers, both at the New Jersey Institute of Technology, had previously developed peptides that can self-assemble into hydrogels when injected into rodents. By incorporating snippets of particular protein sequences into the peptides, the team can give them different functions. For example, Sarkar and Kumar previously developed angiogenic peptide hydrogels that grow new blood vessels when injected under the skin of mice.
To adapt their technology to the brain, Sarkar and Kumar modified the peptide sequences to make the material properties of the hydrogel more closely resemble those of brain tissue, which is softer than most other tissues of the body. They also attached a sequence from a neuroprotective protein called ependymin. The researchers tested the new peptide hydrogel in a rat model of TBI. When injected at the injury site, the peptides self-assembled into a hydrogel that acted as a neuroprotective niche to which neurons could attach.
A week after injecting the hydrogel, the team examined the rats’ brains. They found that in the presence of the hydrogel, survival of the brain cells dramatically improved, resulting in about twice as many neurons at the injury site in treated rats than in control animals with brain injury. In addition, the researchers saw signs of new blood vessel formation. “We saw some indications that the rats in the treated group were more ambulatory than those in the control group, but we need to do more experiments to actually quantify that,” Sarkar says.
According to Kumar, one of the next steps will be to study the behavior of the treated animals to assess their functional recovery from TBI. The researchers are also interested in treating rats with a combination of their previous angiogenic peptide and their new neurogenic version to see if this could enhance recovery. And finally, they plan to find out if the peptide hydrogels work for more diffuse brain injuries, such as concussions. “We’ve seen that we can inject these materials into a defined injury and get good tissue regeneration, but we’re also collaborating with different groups to find out if it could help with the types of injuries we see in soldiers, veterans and even people working at construction sites who experience blast injuries,” Kumar says.
Representing approximately 5% of epilepsy in the civilian population and up to 50% in certain military populations, posttraumatic epilepsy warrants both increased clinical attention and research considerations. In this chapter, we will discuss the important definitions when considering posttraumatic epilepsy including the timing of posttraumatic seizures and the severity of head injuries. We will also review the epidemiology and risk factors for posttraumatic epilepsy in both the civilian population and the military and will describe the association of head trauma and psychogenic nonepileptic seizures. Our clinical discussion focuses on the timing of posttraumatic seizures, the utility of diagnostic testing, treatment of posttraumatic epilepsy, and outcomes of these patients. In addition, we elucidate potential pathophysiologic mechanisms underlying posttraumatic epilepsy and consider its role as a model for epileptogenesis in current and future research. We highlight the relevant studies in each section and underscore the theme that more research is certainly needed in most areas of posttraumatic epilepsy.
If you’re new to the term MOOC it is an acronym for Massive Online Open Course and each year Physiopedia has one for you to take part in for free. The courses Physiopedia have hosted have been hugely successful and have covered a diverse range of topics. This year the topic is Traumatic Brain Injury and it starts today!
The 2019 MOOC aims to provide a basic theoretical understanding of the management of traumatic brain injury in order to equip physiotherapists with sufficient knowledge to manage a person following a traumatic brain injury. This includes assessing impairments, activity limitations and participation restrictions, setting appropriate goals of treatment, formulating an evidence-based treatment plan, implementing treatment and evaluating its success.
Check out the video below to find out more!
This is a completely online course which will take place in Physiopedia’s complimentary e-learning platform Physioplus. You will need need to set up a FREE trial account to access the course, you can do that here. The course will become available on the Physioplus site on 21 October 2019, we place the link at the top of this page and also email it to you. If you’d like to know more about the course check out some more details on the PP page dedicated to the MOOC.
The course will be accredited in 32 States in the USA, Australia and South Africa. That’s right this course comes with free CEUs and CPD Credits if you take part and complete the course.
Don’t forget to choose your favourite T-Shirt for our design competition!
Find out more at https://brainlaw.com/invisible-rain-c… A TBI is a life changing event. But traumatic brain injury is often called “The Invisible Injury” as injuries (and symptoms) will not always be obvious to an observer.
And for those suffering from a TBI it can be difficult to explain how they feel inside.
Every 21 seconds, one person in the USA sustains a brain injury.
And each year over 2.5 million Americans visit the emergency room after suffering a traumatic brain injury, with an estimated 282,000 require hospitalization.
While every TBI is different, and everyone will experience their injury in a unique way, “The Invisible Rain Cloud” attempts to explain some of the common symptoms and feelings an individual may face in their life after brain injury.
The video was created by New York brain injury lawyers De Caro & Kaplen, LLP (https://brainlaw.com), who have been advocating on behalf of individuals suffering from a brain injury for over 30 years.
Find out more at https://brainlaw.com/invisible-rain-c…
This article evaluates whether specific drugs are able to facilitate motor recovery after stroke or improve the level of consciousness, cognitive, or behavioral symptoms after traumatic brain injury.
After stroke, serotonin reuptake inhibitors can enhance restitution of motor functions in depressed as well as in nondepressed patients. Erythropoietin and progesterone administered within hours after moderate to severe traumatic brain injury failed to improve the outcome. A single dose of zolpidem can transiently improve the level of consciousness in patients with vegetative state or minimally conscious state.
Because of the lack of large randomized controlled trials, evidence is still limited. Currently, most convincing evidence exists for fluoxetine for facilitation of motor recovery early after stroke and for amantadine for acceleration of functional recovery after severe traumatic brain injury. Methylphenidate and acetylcholinesterase inhibitors might enhance cognitive functions after traumatic brain injury. Sufficiently powered studies and the identification of predictors of beneficial drug effects are still needed.
According to MSKTC, “Drinking increases your chances of getting injured again, makes cognitive (thinking) problems worse, and increases your chances of having emotional problems such as depression. In addition, drinking can reduce brain injury recovery.” Traumatic brain injury (TBI) has many side-effects including cognitive problems, depression, difficulty with balance and alcohol only intensifies these challenges. Alcohol can cause dizziness, staggering and falling, and this is not good for anybody. In fact, many TBI injuries are alcohol related. Maria Magana recants how she got her TBI by saying, Sadly my TBI was from an alcohol/benzo issue. Yeah I was dumb as hell, but I learned through the hardest way. So I really hate talking to other TBI people about it.” Alcohol related TBI injuries could be more common than you think. Additionally, accidental alcohol related deaths are not unheard of. Wendy Harris said, “ My uncle was a TBI survivor and he recently passed away bt drinking, falling, ang hitting his head.” Both the coordination issues that comes with alcohol and the balance issues with TBI, together, can cause a deadly combination. Furthermore, MSKTC continued by saying, “ says, “Traumatic brain injury puts survivors at risk for developing seizures (epilepsy). Alcohol lowers the seizure threshold and may trigger seizures.” All of these complications are unnecessary troubles for a TBI survivor to have and we forgot to mention that the majority of TBI survivors are on medications such as muscle relaxers, blood thinners, and seizure medications that more than often counteract with alcohol. With that said, let’s throw the anti alcohol disclaimer out the window and explore the pros and cons of alcohol consumption post TBI.
For most, an alcoholic drink or two is a nice way to celebrate an occasion or to go with a nice meal. Some actually despise all alcohol – the taste, feeling, and smell.
But those who love alcohol love the sensation of being tipsy, wild, and feeling out of control. The unusual feeling is also encouraged by peers through a form of peer pressure and FOMO (fear of missing out). You’re at a party, and friends are drinking all around you, so why wouldn’t you, too? Roger Osburn, a fellow TBI survivor answred this question by saying, “Alcohol exacerbates my TBI related challenges. I do not drink anymore but sometimes will have a glass of wine, always remembering later why I don’t. It can be challenging socially.”
For people with alcohol addictions, it’s a way to feel “numb,” separate themselves from reality, and to cope with various mental illnesses. The problem is, individuals with TBI have higher rates of alcohol abuse than their peers, according to NCBI. Additionally, according to MSKTC, “Up to two-thirds of people with TBI have a history of alcohol abuse or risky drinking.” Alcohol consumption and TBI are closely related as is TBI and alcoholism. While recreational alcohol is tolerable for the average person, for a TBI survivor, such behavior is ill-advised. Below is a testimony given by a TBI survivor who requested to stay anonymous. With that said, This is only anecdotal experience, and cannot speak for everybody, and if you would like to share your experience with TBI and alcohol please do so in the comments below.
“Do you want a glass of wine?” A friend I met in the hospital, Ben, came to visit me at my house with a bottle of wine. Ben attempted to make a generous greeting by brandishing a bottle of wine however, I was skeptical in taking part of his offering as I am recovering from a traumatic brain injury. I did not know how alcohol would affect my brain recovery, how alcohol would interfere with my medication, or how alcohol would make me feel. Additionally, I have to get my blood checked regularly, because I am on blood thinners, and I did not know how thin my blood would get by consuming wine. Despite my reluctance, I threw my caution to the wind and I told myself, “I was shot in the head, a glass of wine will not hurt.” I began sipping the wine and next thing I knew it was time to take my muscle relaxers, this was not good. I took my medication and over the course of the night I took three more doses of TBI related medications which was dangerous, stupid, and made me very sick. For the next week my stomach was torn up, I was exhausted, and both my body and mind felt like it was hit by a dozen semi trucks and I still had therapy eight hours a day, everyday for the next week. Luckily I am confined to a wheelchair because had I been walking around drunk or buzzed I would be putting myself at risk for a second brain injury.My experience with the wine I drank was so bad that I cut Ben off and told him we could not hang out again.”
April has suffered debilitating symptoms for over nine years since an illness left her with a severe traumatic brain injury (TBI). After just six weeks of neurofeedback, she has experienced significant improvement. This interview with April, her daughter, and Mike Cohen of the Center for Brain Training explores the power neurofeedback can have in people’s lives, even many years after a brain injury occurs.
Neurofeedback, or brain training, can help people suffering repercussions of traumatic brain injury, post-concussive syndrome, and stroke.
A transcript of the video is available below:
A: She is a walking miracle for sure.
A: I mean, even now if you look at her actual MRI or anything, there is so much damage that people thought that she should be a vegetable or something like that by now. So after she got out of the hospital she couldn’t read, she couldn’t write, she had no depth perception. She was very out of it. She didn’t remember our names or anything like that.
M: What are you both seeing change since you’ve been training your brain with the neurofeedback?
Ap: My communication is lot better. My finding direction is a lot better.
A: I think she’s becoming more of herself again. She’s getting some of her personality back. She has always been pretty feisty. She keeps going no matter what happens. She seems to be getting a lot better. She can tell her right from left, which is a big deal. She is becoming a lot more sharp, I guess, mentally. She definitely has a ways to go, but this is improving her for sure. I think that a lot of things are possible with her because, before she got sick, she had so much drive and she was very inventive and creative and never let anything in life stop her. She’s still like that now, but she is really having a hard time putting her thoughts together and being organized, and the sharper her brain gets, I think that she could take that a long way.
M: When I met you, one of the things I noticed, April, was that you were almost like in a fog.
Ap: Yes. I’m much more alert.
M: So you are better able to communicate with other people now?
Ap: Yes, much better. Sometimes I have to hear what they said, and I can hear what they said but I couldn’t process it all. This is very encouraging. It’s amazing how I am seeing the brain come back around.
M: Did any of your doctors ever mention anything like this?
M: Did any of the other therapies ever help your brain like this?
M: I am just excited for you that your brain seems to be waking up.
M: Is that what it seems like?
Ap: Yes, in so many ways. I mean, I had other things; it’s very interesting, like the taste and the smell. You know, that didn’t really work.
A: Yes she had no taste, no smell for the most part. Even her vision changes all the time. Like when she goes to the doctor, everything is different all the time, so they can never give her glasses or contacts that actually work the whole time, which is really interesting, but it seems like since she has been doing the brain therapy, some of that has been coming back.
M: And you are interested in medical and going to a med school, is that right?
A: Yes, definitely. So the brain is definitely something that I am really interested in now, especially after seeing this, because doctors don’t seem to use this, like you had said, so I would definitely be interested in learning more and seeing how far you can go with it.
Objective: Prolonged mental fatigue and cognitive impairments are common after a mild traumatic brain injury (TBI). This sets limits for rehabilitation and for regaining the capacity for work and participation in social life.
Method: This follow-up study, over a period of approximately 5.5 years was designed to evaluate the effect and safety of methylphenidate treatment for mental fatigue after a mild TBI. A comparison was made between those who had continued, and those who had discontinued the treatment. The effect was also evaluated after a four-week treatment break.
Results: Significant improvement in mental fatigue, depression, and anxiety for the group treated with methylphenidate (p < .001) was found, while no significant change was found for the group without methylphenidate. The methylphenidate treatment group also improved their processing speed (p = .008). Withdrawal produced a pronounced and significant deterioration in mental fatigue, depression, and anxiety and a slower processing speed. This indicates that the methylphenidate effect is reversible if discontinued and that continued methylphenidate treatment can be a prerequisite for long-term improvement. The effect was found to be stable and safe over the years.
Conclusion: We suggest methylphenidate to be a possible treatment option for patients with post-TBI symptoms including mental fatigue and cognitive symptoms.
Long-term mental fatigue and cognitive impairment are common after a mild, moderate or severe traumatic brain injury (TBI) and these can have a significant impact on work, well-being and quality of life (1). Fatigue and concentration deficits are acknowledged as being one of the most distressing and long-lasting symptoms following mild TBI (1). There is currently no approved treatment (2), although the most widely used research drug for cognitive impairments after TBI is methylphenidate (3). A few studies have used methylphenidate for mental fatigue after TBI with promising results including our own (4,5). Other clinical trials of drugs have reported improvements in mental fatigue ((−)-osu6162 (6)) or none ((−)-osu616, modafinil (7–9)).
In our feasibility study of methylphenidate (not placebo controlled) we reported decreased mental fatigue, improved processing speed and enhanced well-being with a “normal” dose of methylphenidate compared to no methylphenidate for people suffering from post-traumatic brain injury symptoms (4). We tested methylphenidate in two different dosages and found that the higher dose (20 mg three times/day) had the better effect compared to the lower dose. We also found methylphenidate to be well tolerated by 80% of the participants. Adverse events were reported as mild and the most commonly reported side-effects included restlessness, anxiety, headache, and increased heart rate; no dependence or misuse were detected (10). However, a careful monitoring for adverse effects is needed, as many patients with TBI are sensitive to psychotropic medications (11).
Participants who experienced a positive effect with methylphenidate were allowed to continue the treatment. We have reported the long-term positive effects on mental fatigue and processing speed after 6 months (12) and 2 years (13). No serious adverse events were reported (13)(Figure 1). In a 30-week double-blind-randomized placebo-controlled trial, Zhang et al. reported that methylphenidate decreased mental fatigue and improved cognitive function in the participants who had suffered a TBI. Moreover, social and rehabilitation capacity and well-being were improved (5). Other studies evaluating methylphenidate treatment after TBI have focused only on cognitive function reporting improved cognitive function with faster information processing speed and enhanced working memory and attention span (14–21). A single dose of methylphenidate improved cognitive function and brain functionality compared to placebo in participants suffering from post-TBI symptoms (22,23). Most of these have been short-term studies covering a period between 1 day and 6 weeks and included participants suffering from mild or more severe brain injuries.
This clinical follow-up study was designed to evaluate the long-term effect and safety of methylphenidate treatment. We also evaluated the effect after a four-week treatment break and compared the subjective and objective effects with and without methylphenidate. Patients who had discontinued methylphenidate during this long-term study were also included in this follow-up, as it was our intention to compare the long-term effects on mental fatigue in patients with and without methylphenidate treatment.