This week our topic focused around bipolar disorder. Bipolar disorder is characterized by continual changes in mood that last over a long period of time. These moods cycle between depression and mania and can last in one part of the cycle for weeks at a time. The symptoms for mania include being easily distracted, little need for sleep, poor judgment, poor temper control, reckless behavior, elevated mood, extreme involvement in activities. There are also two types of bipolar disorder, 1 and 2, bipolar 1 is characterized with the mania symptoms, while bipolar 2 still has mania symptoms, but not as intense. Some of the other symptoms and possible treatments can be found on this link: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001924/
It is often difficult to characterize and quantify the extent of the depression or mania symptoms so it is often challenging to diagnose true bipolar disorder. It often takes many sessions over a long period of time to diagnose. Often times doctors will ask about family history and ask about your recent behavior and mood swings to try to diagnose, but this is very difficult. The official psychologist diagnostic manual called the DSM even states at the end that these episodes of depression/mania could be bipolar if they can’t be explained better through schizophrenia disorders, delusion disorders or other unspecified disorders. Here is the link that include the descriptions from the DSM: http://www.fortunecity.com/campus/psychology/781/dsm.htm This is extremely frustrating because there is no clear test or set of symptoms to declare that an individual definitively has bipolar disorder. Simply put, it seems as though this disorder is diagnosed through the process of elimination.
Treatment is just as difficult if not more challenging to pinpoint. Our article this week focused on three major medications for the treatment disorder, they include lithium, valproic acid and carbamazepine. These medications are classified as “mood stabilizers” because they try to level out the mania and depressive symptoms however they work better on the mania symptoms and no one is sure why. The different medications work differently on different individuals and the different types of bipolar disorder and since it is so hard to diagnose often times individuals are on these drugs on a “trial and error” method. They will be prescribed one treatment and if that doesn’t work they move on to the next and the next and the next. Along with these mood stabilizers, doctors may also prescribe antiseizure medication, antipsychotics and antidepressants. Some patients may even be on all of the drugs at once with many harmful side effects and when the treatment starts working and the symptoms lessen, doctors may be unable to pinpoint which drugs is the effective drug. Treatments for bipolar disorder other than drugs include electroconvulsive therapy (small shocks to the brain), transcranial magnetic stimulation (sends pulses to a specific area of the brain) or even talk therapies and support groups. For more information about the drugs, side effects and other treatments please follow this link: http://mentalhealth.gov/health/publications/bipolar-disorder/complete-index.shtml
"Delayed Concussions"
I was a football student manager from 6th grade until I graduated high school so I saw my fair share of concussions but what I had never seen was a delayed concussion that happened days after the actual head trauma happened, until it happened to my cousin. That days practice started out like any other, with drills and running plays but throughout practice everyone kept asking where my cousin was and why he wasn’t at practice. The answer was that I didn’t know but not too much longer after we saw him coming down the hill but there was something off about him. His jersey was on backwards and he was having a hard time walking. When he got to the field he ran to the wrong group and continuously asked where the linemen where even after our coaches told him multiple times. When he finally got to the linemen group, where I was, he was in really bad shape. He could barely stand or talk and his coordination was extremely poor. Now in his past he had a history of drug use so everyone thought there was a chance he was high and that was why he was acting strange. Because of this thought and me being his cousin, everyone insisted that I take him home before the coaches realized that he might be high. So I did just that! I pulled him aside and, in my best stealth mode, started walking him up the hill back to the locker rooms. However, with the state he was in and his size (me=5’1″, 125 lbs, him= 6’2″, 275 lbs) carrying him up the hill was really hard. I knew something was really wrong when he looked down and asked why was the ground covered in ice cubes….there was no ice it was the grass. Luckily while walking with him a friend of ours saw us and offered to take him home. About 30 minutes later my mother called and said they were taking him to the hospital because they couldn’t come up with any reason why he was acting the way he was.
At the hospital, the ER doctor told us he was suffering from a closed head injury but when the neurologist came to see him he told us my cousin had a severe concussion. This was odd to us because we knew he hadn’t suffered a head injury in the few days preceding the incident. But then my cousin remembered that at our last game, almost a full week before, he had a helmet to helmet collision with a player on the other team.
But the real question is what’s the difference between a closed head injury and a concussion?
There really isn’t a difference. A concussion is thought to be a form of a closed head injury along with brain contusions or bruising of the brain, intracranial hematomas or bleeding in the brain after being forced against the inside of the skull, and diffuse axonal injuries or damage to nerves in the brain. Closed head injuries are any injury to the head that does not penetrate the skull. They are usually caused by blows to the head because of traffic accidents, fall, assaults, or sports injuries.
Definitions of concussions themselves vary but according to the Mayo Clinic, concussions are any head injury that temporarily affects normal brain functions. Effects are usually temporary but can sometimes cause permanent problems. Most concussions are mild and do not result in loss of consciousness but this is not always the case. People suffering from a concussion can display immediate symptoms such as headaches, nausea, dizziness, slurred speech and vomiting. They can also be confused, have difficulty with coordination and difficulty with concentration. In some cases, like my cousins case, symptoms do not show up for hours or even days after the incident.
http://www.allabouttbi.com/closed-head-injury/
Concussions: A Big Impact on Life
Newsworthy
Concussions have been creating much fervor in the news recently. Increasingly, high schools, universities and other educational institutions have been implementing policies meant to protect athletes from lifelong brain dysfunction caused by concussions. The NCAA requires that: all student athletes receive information about concussions, all NCAA institutions have a process in place to evaluate athletes for possible concussions, and that athletes exhibiting signs of concussion are removed from play and are not returned until cleared by a physician of physician designee.1 Students are not the only athletes affected by new policies shaped by awareness of the dangers of concussions. Both the NHL and NFL have been making changes to the equipment, policies and evaluation players undergo to avoid serious brain damage that has been associated with multiple concussions.
Concussion Symptoms
A concussion is caused by trauma to the brain and is by a loss of consciousness or altered level of consciousness, but people can have concussions and not realize it. Symptoms include headache, memory loss, nausea and vomiting, disorientation and experiencing a loss of time.2 Changes in behavior and mood are also indicators of a concussion. Much of the current discussion has revolved around the long-term effects of multiple concussions, which is also known as chronic traumatic encephalopathy (CTE). Although there are not many confirmed cases of CTE, more than 90% of them were seen in athletes and the symptoms are severe. In the earliest stages patients experience some psychotic symptoms and erratic behavior. Later stages include dementia, gait abnormality and symptoms associated with Parkinson’s Disease.3 what can be done to avoid these problems as an athlete or even just going through day-to-day life.
Your Brain on Concussions
The paper we read this last week described the timetable of events in the brain after experiencing a concussion. When the brain receives a traumatic injury it sets off the neurons, causing excitation in the brain and the movement of many ions, like sodium and potassium, out of balance within brain cells. To get things back on track the brain uses lots of energy to pump the ions back to their proper places. This creates an energy crisis within the brain, which likely is the reason for symptoms such as memory loss, disorientation and unsteadiness. There is also a reduction in the amount of blood flowing to the brain that only further exacerbates the energy crisis. It takes the body a number of hours to recover from the energy crisis and days to repair the damage done to brain cells due to the energy crisis and the trauma itself. Unfortuanatly, other than prevention there isn’t a good way to protect the body from concussions, yet.
Concussion treatment
So far, the best treatment for concussions is to rest and avoid overstimulation so the brain has time to fully recover. This is because there are a number of problems with treating a concussion with medications. One of the primary problems is with diagnosis. Most of the problems that a concussion causes in the brain happen in less than ten minutes. This leaves a very small window of time to evaluate the trauma, diagnosis the concussion, and administer the treatment. Because there are essentially no medications without side-effects it would likely not be appropriate to administer a concussion treatment every time a person gets knocked-around, “just in case.” A second problem with treating a concussion is finding the problem to treat. Should the excitation be treated, or the lack of blood flow, or the need for energy? Which is the underlying cause of the symptoms, and which if manipulated will cause the fewest side effects? As always, researchers are looking into these questions and any day a great discovery could be made. Until then, play hard, but play safe and protect your noggin.
1. http://www.ncaa.org/wps/wcm/connect/public/NCAA/Student-Athlete+Experience/Student-Athlete+Well+Being/Concussions
2. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001802/
3. http://www.sportsmd.com/Articles/id/44.aspx
"Spiritual Disorder" or Neurological disorder? What are we doing?
Neuro degenerative disorders were not always neuro degenerative disorders. Before the enlightenment and its emphasis on naturalism and empirical study, neuro degenerative disorders were spiritual disorders. These “spiritual disorders” were never naturalized, but were considered a distortion of the soul. The naturalized language of modern day psychology and neuroscience did not make its appearance until the 19th century. The disordered souls were ostracized by their respective communities. And when rare help was called for, it was the religious healer, the back alley mystic, that answered the call. The mystic may have had some balm or powder with its corresponding superstitions, but the primary method of cure was prayer or meditation, direct links to the soul.
Prayer, meditation, and an overall spiritual emphasis, are things modern medicine is slowly forgetting about. Our reductionist understanding of the mind is taking over. We have realized the power of direct intervention in the brain and with this we have reinvented “soul disorders” as neurological disorders; problems of the brain. People are no longer inflicted with despair; they just have major depressive disorder. People aren’t driven to great anxiety by past sins or moral infractions, they just have obsessive-compulsive disorder. A new paradigm has brought with it new words and new treatments, but the ailment is the same, and the new treatment’s do not target the soul directly, but the brain directly.
Parkinson’s disease, although recently naturalized, was around long before neuroscience was. Parkinson’s is understood as a loss of cells in the brain region called the substantia nigra that produce the chemical messenger dopamine. Dopamine plays a vital role in muscle movement and coordination. The loss of the dopamine producing cells in Parkinson’s causes its well known symptoms; the jerkiness, the shaking, the rigidity, and later cognitive decline.
Parkinson’s is a disease that the new paradigm cherishes. Its origins are fairly obvious, and are under little scientific dispute. Certain cells are lacking; this is something we can measure. The new paradigm holds Parkinson’s up as a model of what neuroscience is capable of. We can identify what’s wrong in the brain, theoretically go in, and fix it. But Parkinson’s leads us down a path we have already started on. Depression as a spiritual disorder is ignored. A bad mood as a spiritual funk is ignored. Every mental event is being fathered by the new paradigm and the spirit, the soul, which we cling to dearly, is taking a back seat. Is something wrong here? What should we think when a child is in a bad mood and the parents take him in for some anti-depressants? Have we lost touch with ourselves?
The new paradigm should be put on a pedestal and it should be a guiding force in our decisions. It works. Without the new paradigm people with Parkinson’s would still be getting help from healing balms and ritualistic chants. But we need to be aware of what the new paradigm is doing. We need to be on our toes. Neuroscience is progressing much faster than humanity’s intuition, and it seems to me that we do not know where we are headed with this technology. Where do you think we are headed? What do we make of the soul when all ailments are ailments of the brain? What do we make of the soul, period? It is the case that we still love and cherish our soul even though we ignore it.
Concussions in Elementary School Children
The topic of discussion this week was about the mechanisms underlying concussions and the many side effects that they can produce. The mechanical force of a blow to the head can cause chemical changes in the brain and alterations in signalling. These alterations can include influxes of calcium within cells that cause disruptions in metabolic functions that can cause permanent damages to cognitive functioning and memory systems.
The most heated area of discussion regarding concussions is in the area of professional sports and how to deal with athletes returning to play. However, an area that may hit a lot closer to home is concussions among elementary school aged children. Some elementary schools now send notes home from the nurse’s office if children fall on the playground or seemingly knock their head too hard. While these measures are safeguards for parents to know what to look for in their children when they come home, the extremities of the measures that now days need to be taken may be seen as a little extreme. Nonetheless, concussions among elementary aged is an interesting and important topic during those formative years.
According to guides that are published by various school districts for educators, elementary kids are more likely to report physical problems or cognitive problems relating to anxiety or stress after an accident that may be due to a concussion. The key to this then is to collaborate with school teachers, nurses, playground staff, and parents to understand the nature of the injury and to help with recovery and improving cognitive learning side effects. Some classic symptoms that teachers can look for are students that get tired in class, are bothered by noise or light, easily distracted, trouble learning new material, problems with memory, or being easily overwhelmed with information. Teachers can help students during the time of experiencing cognitive difficulties by adapting classroom material, giving more time for assignments and tests, providing easier transitions, and allowing students to work in more quiet settings.
An understanding of these symptoms to look for and ways that they can aid in student recovery is important even for teachers of young children.
Concussion recovery time varies on individual basis
Concussion is a common accident experienced by people of all ages. It can be a result of a fall, a hit to the head or any type of traumatic brain injury. Sports related concussions in athletes are among the most common incidents. We discussed about the neurometabolic cascade of concussion in class as it is one of the important areas of neuropsychological diseases. When a traumatic brain injury occurs, the neural cells are overly activated (depolarized and initiation of action potentials) as a result of mass release of excitatory neurotransmitters. When the cells are overly stimulated, there is a massive efflux of potassium, that is potassium molecules going out of the cells in great amounts. As a result, sodium-potassium pump has to work harder to maintain the normal sodium and potassium levels both inside and outside of the cells, called maintaining homeostasis process. The pump is ran by the activity of enzyme ATPase and this ATP is provided from the break down of glucose in the cell, called glycolysis. During the events following the traumatic brain injury, there is a demand for increased ATP to run the pump and hence increase breakdown of glucose called hyperglycolysis occurs. Other important metabolic events include increase lactate accumulation from increased glycolysis, and increased Calcium influx (large amount of Calcium coming into the cells) which leads to impaired metabolism of mitochondria, cell’s main ATP production center. When mitochondrial ATP production is decreased due to impaired metabolism, cell death can occur as a result of energy deficiency and these cell deaths can result in cognitive impairments and amnesic symptoms seen in Concussion.
In this blog, I will discuss the different recovery time required for concussed patients according to the age group. In the mild cases of concussion, the increased release and activities of neurotransmitters can resolve back to normal within a few days due to body’s homeostasis mechanisms. The recovery time differs not only with the age group but also with each individual. Individual differences in recovery time between young or middle-aged concussed patients have been detected in research studies. Elderly concussed patients are found to be affected more and take longer recovery period even with milder brain injuries.
According to the research article by Gagnon,et.al, 2009, a gradual and closely-supervised active rehabilitation program for individual interventions are needed for children who are slow to recover. The article suggested underlying principals for development of intervention according to Montreal Children’s Hospital Rehabilitation After Concussion (MRH-RAC). The MCH-RAC principals include-Aerobic Activity, Coordination/Skill Practice, Visualization of Positive and Successful Activities related to Preferred Physical Activity, and Education and Motivation. The study suggests that children and adolescents who are slow to recover should participate in controlled and closely monitored rehabilitation and individualized intervention is sometimes necessary for concussed children. Exercise is also mentioned to have a positive impact on recovery since it promotes neuroplasticity (the growth of new neurons). Hence, according to Gagnon et.al, active rehabilitation and exercise are recommended recovery interventions for concussion in children.
A study by Mcclincy.et.al, 2005, reports that American athletes suffer approximately 300,000 concussive injuries in a year and 19 percent of participants are athletes who are involved in sports such as football and rugby. The article mentions current recovery measures such as Colorado guidelines, and American Academy of Neurology guidelines, According to the article, these scales diagnose concussion on a three point scale with grade 1 (mild), grade 2 (moderate), and grade 3 (Loss of conscious). For grade 1 injuries, the athletes can return to play on the same day of injury and for grade 2, within 1 weeks of injury. It was also mentioned that all concussion grading scales assume that all athletes should heal from concussive injury within 7 days. However, the study found out that the scales generalize ages, playing levels, gender and individual physiological responses concerned with the recovery process. The study used computerized neuropsychological testing ImPACT which is supposed to provide more accurate individualized results than traditional paper and pencil tests. The results of the study indicated that the cognitive deficits lasted at least 14 days in a sample of collegiate and high school athletes. The study also found out that 5 percent of the grade 1 concussions took 1 week, 34 percent of the grade 2 injuries took 2 weeks, and some of the grade 3 concussions took about a week and some took 2 weeks to recover. Hence, the study points out that traditional grading scales and recovery time according to the grading are not reliable on individual basis of recovery.
Of all the age groups, concussion in elderly patients are believed to take the longest to recover and harder to diagnose due to other neural complications that come with aging. According to the article ‘Outcome after traumatic brain injury: Effects of aging on recovery’ by Testa.et.al, 2005, elderly patients with traumatic brain injury have’ higher mortality and worse functional outcome than younger patients even with less severe injuries. The article states that elderly patients are more likely to suffer mood decline, impaired psychosocial and cognitive functioning and less complete recovery compared to younger patients. This increased vulnerability of the aging brain, the article states, is due to decreased brain reserve to make up for the damaged neural tissues. The article suggests that age is a risk factor in diagnosing and recovery process of concussion in elderly patients. Hence, rehabilitation efforts for these senior patients should consider other factors related to aging and cognitive decline.
By looking at the studies that are mentioned above, it is important to note that recovery time from concussion or traumatic brain injury will vary with the individual’s age, severity of the damage, and physiological responses. Therefore, it is not accurate to generalize the symptoms of children, adolescents, athletes, and elderly patients depending on the popular grading scales and estimate the recovery time according to those scales.
TBI in the Military
At age 27, former Army sergeant Jordan Edwards should be in the prime of his life. He served two tours of duty in Iraq before retiring from the service and returning to his home and family in the Midwestern US.
However, all is not well. Jordan has daily headaches, sees spots in his vision, has lost part of his hearing, and frequently forgets things. He struggles with regulating his emotions and mood, and is often irritable. Since returning from Iraq, Jordan divorced his wife, attempted suicide multiple times, and is currently living with his mother because he can’t keep a job. Even worse are the legal fees and jail time incurred from his reckless and irresponsible behavior. What went wrong?
When Jordan was in combat in Iraq, he was present during explosions of rockets, mortars, and IED (improvised explosive devises). The blasts of these explosions caused him to have a TBI—traumatic brain injury. The force of the blasts jostled his brain in his head, damaging areas of it that will remain impaired indefinitely.
Since the US wars in Afghanistan and Iraq began over a decade ago, reports of TBI in soldiers like Jordan have risen sharply. Estimates inside and outside the US government show that approximately 12%-20% of soldiers returning from these tours have a TBI or should be diagnosed with one. Getting care for these injuries has been a difficult process, marked by considerable lag in both recognition of the condition and research into treatment options. The sheer volume of returning soldiers reporting TBI symptoms, however, has forced Veterans’ Affairs and the medical community to address the demand for treatment and compensation for these injuries.
What is TBI?
“TBI” is a broad term that covers basically any brain injury due to a biomechanical force. A concussion is generally considered to be a mild TBI, with mild symptoms that eventually go away. More severe TBIs, however, can result in long-lasting physical, behavioral, cognitive, and/or emotional problems. Common effects include loss of function or movement of a limb (or side of the body), loss of a sense like vision or hearing, memory impairment, depression, and irritability. While symptoms like movement or memory problems are easily recognized, others—like altered judgment and depression—are not. This makes diagnosing and treating the full symptoms of TBI very difficult for physicians.
Exactly how a blow to the head causes the diverse outcomes of TBI isn’t known completely yet. What we do know, however, is that the force of the blow can definitely damage blood vessels and tissue due to the motion of the brain against the skull, possibly twisting and stretching fibers deep in the brain. This can cause cellular structures to break down and chemicals called neurotransmitters to be released abnormally in the brain.
One neurotransmitter, called glutamate, is the main chemical that causes brain activity. It is “excites” nerve cells to send chemical and electrical signals throughout the brain, increasing activity. After a TBI, there is too much glutamate in the brain at first. This can be damaging to cells because too much activity wears them out and can kill them. What happens next is that too much activity uses up the brain’s supply of energy and oxygen. The brain slows down as tissues swell, acid builds up in cells, and the system “powers down” due to malfunctions. The result is more cell damage and death.
This power failure and dysfunction affects many other neurotransmitters, chemicals, and minerals like calcium and magnesium, substances that are vitally important not only for a healthy brain but also for things like learning, memory, attention, clear thinking, emotion, and good judgment. Damage to specific cells and tissues can permanently alter a person’s functioning in these areas.
Doctors determined that Jordan Edwards’ TBI included damage to cells in the frontal lobes. After returning from Iraq, Jordan had been involved in alarmingly risky incidents: he had crashed his motorcycle at 155 mph on the highway and had gotten deeply involved in dealing drugs, landing him in jail. An assessment of his brain suggested that his TBI had damaged his ability to make good decisions and grasp moral and social values, leading to his law-breaking activities. Jordan’s case is only one example of how the cell damage in TBI can lead to BIG problems with brain function.
Treating TBI
With a serious health concern like TBI, the main question is how to treat this problem. Unfortunately, while physical therapy and rehabilitation can help people with less severe TBIs get some of their functions back after brain injury, so far little has been found that can stop the cell damage and chemical dysfunction from occurring in the brain. The most damage happens not at the impact of the trauma but seconds later, when chemicals start building up and the brain runs out of resources. If a treatment could target this process, it could be given right after injury to prevent cellular damage from occurring. Researchers are still working on this question and, due to the complex nature of TBIs, will be probably working on it for a while.
Other types of treatment target the social, emotional, and behavioral damage of TBI. Since depression and PTSD commonly occur along with TBI in veterans returning from war, counseling and therapy can help them learn to cope with their traumas and become productive members of society again. Some newly-developed cognitive-behavioral therapies aim to target behavioral and neurological problems including aggression, memory dysfunctions, and attention deficit by “reteaching” patients how to use manage these skills. However, the results of these interventions have not been definite, and more research is needed investigate their effectiveness further.
Legal issues in treating TBI in the military
For veterans returning home to the US with TBI, it has not always been easy for them to get proper care. Next to PTSD, TBI is also commonly overlooked and under-diagnosed. Frequently, while in combat soldiers are not aware that they experienced a TBI, or, if they knew they were injured, would re-enter combat or be ordered back into combat too soon. Not enough rest after an injury can make the damage even worse. Once back in the US and away from the hectic battlefield, however, soldiers were still not getting the proper attention for TBI.
The US Department of Veterans’ Affairs has been sharply criticized as being neglectful due to its slowness to fully recognize a wide spectrum of TBI. Certainly, diagnosing TBI can be very difficult since some injuries can appear more like psychiatric conditions. But a lot of the issue comes down to money: what kind of treatments should government insurance pay for? What kind of TBIs should the US grant disability compensation for? A soldier that had his leg blown off by a mine would have no problem securing treatment and disability, as would probably a veteran with a severe TBI who lost function on one side of his body and needs rehabilitation. However, soldiers like Jordan Edwards who have suffered profound cognitive and psychological disturbances and, as a result, can’t hold a job and function well in society have had difficulty getting a VA doctor to even look at them, much less their application for disability compensation to be accepted.
As awareness of TBI has increased over the last few years, the VA has come around. Currently trying to improve their image in brain injury treatment and make up for their past failures, they are launching TBI initiatives that include partnerships with brain trauma research groups, a TBI registry program, and the creation of the Polytrauma/TBI System of Care, a program that attempts to recognize the wide variety of symptoms and disabilities resulting from brain injury. Additionally, they have widened the criteria for disability compensation in the case of brain injury. As awareness and research into the mechanisms and treatments for TBI continue to increase, US veterans can look forward to better, more comprehensive care for their injuries.
Effect of Double Concussions
Concussions have become a hot topic in sports. Athletes in sports like football and hockey are getting bigger along with their hits. This has made concussions more prevalent and an issue that arises is the time period an athlete should sit out before returning from a concussion. The answer to this can be found in the mechanism and neurometabolic cascades of a concussion.
A concussion is a type of traumatic brain injury caused by a blow to the head or any motion that causes the brain to shake within the skull. After this happens, an abrupt indiscriminant release of neurotransmitters and a rapid flow of ions occur. This disrupts the membrane potential in the neurons that plays a very large role in cell signaling. To restore the natural membrane potential to carry on with normal cell signaling, the sodium-potassium pump must work extra hard. To do this, the cell requires a large increase in ATP and a large jump in glycolysis to produce the ATP. This hypermetabolism soon leads to hypometabolism as glucose supplies in the brain run low. During this time, an increase of calcium ions and a decrease on magnesium ions appears in the neurons along with a increase of lactate from the spike in glycolysis. The increase of calcium ions can lead to free radical productions, cytoskeletal reorganization, and activation of apoptotic genetic signals. A decrease in magnesium ions may lead to neuronal dysfunction via multiple mechanisms because of magnesium’s important role as a cofactor in glycolysis.
This cascade resulting from a concussion leaves many areas of vulnerability for a second injury. During the time of hyperglycolysis, the cell is trying to rebuild the membrane potential that was disrupted by the initial concussion. If a second concussion occurs during this time, all the work that the sodium-potassium pump as done will be wiped away. But this time the cell won’t have enough glucose to power the action of the sodium-potassium pump because most of it was used up from the first injury. A similar result will happen if the second injury occurred during the period of hypoglycolysis. Another area of vulnerability is during the period of increase intracellular calcium. Calcium levels may impair mitochondrial metabolism and reduce to the production of ATP. But if an injury happens, the cell won’t be able to go into hyperglycolysis to reinstate the membrane potential because of this reduction in the ability to produce ATP in the mitochondria. Also, another increase of intracellular calcium can lead to cell death by activating proteases that promote apoptosis. The period of higher concentrations of calcium lasts for 2 to 4 days. Similar side affects can occur from the decreased concentration of magnesium. Since magnesium plays a crucial role in the process of glycolysis, so if another injury occurs, it will again decrease the concentration of magnesium inside the cell and inhibit glycolysis, which is highly needed.
The cascades that arise from concussions have dramatic affects of everyday processes that take place in the brain. Membrane potentials are disrupted which inhibits normal cell signals. Glycolysis is a very important process that is disrupted after a concussion as it goes into overdrive to drive the sodium-potassium pump and reinstate the membrane potential. Adding a second injury to a concussion during the recovery period can be detrimental to a brain because of how the brain recovers from the first concussion. The second injury will setback all the work the brain has done to heal from the first injury but the same resources are not as readily available.
Concussions and the 21st century
As I have mentioned in previous blog posts, today we expect there to be a pharmaceutical solution for every medical condition imaginable. Though this mentality doesn’t transfer to concussions. When I think of concussions I normally think of the phrases “walk it off” or “you should take a break”. It’s a weird thought that someday after getting a good whack to the head to be told, “Hey you don’t look so good, go take some __blank__ medication”.
Today we are starting to see many different administrations bringing the concussion issue to the front of their concerns. High schools, colleges, and professional sport organizations all have to decide where they sit on the issue. Do teams take out their fan favorites and risk losing, just to possibly save them some brain cells down the line?
In the eyes of sports organizations in perfect world an athlete could get a concussion, take a pill, and be right back on the field with no worries of consequences. So how close are we to this “perfect world”. To answer this question we need to look where current research stands. Luckily I found an article (1) that was published only 6 months ago that deals with this exact issue.
PGI-02776 is a prodrug aimed at minimizing the effects of a concussion. When a concussion occurs many different processes are initiated. As you can see in the figure there are a few chemical imbalances that occur after getting hit, PGI-02776 is aimed at preventing the glutamate increase. One might think that Glutamate shouldn’t be a concern because its increase is the smallest, but it also must be kept in mind that Glutamate is also one of the most complicated. Glutamate has many different effects in the body and brain so keeping its concentration level is necessary for a good health.
So in any good scientific experiment it is a good first test to see if a drug is actually doing anything. When PGI-02776 was tested with a concussion the glutamate produced was 20% of what was seen with no drug. Which could be considered successful results. So what other results are seen? Researchers were interested in cognitive results of this drug, so they developed a maze for rats. With this maze the drugs affects on long-term and short-term memories could be tested.
There were three different groups of rats:
- Rats with no Traumatic Brain Injury (TBI)
- Rats with TBI given PGI-02776
- Rats with TBI given placebo
As would be expected the group of rats with no TBI were able to finish the maze fastest and had the best rate of learning. Rats that had a TBI and were given a placebo finished the maze slowest and had the slowest rate of learning. Resulting in our PGI-02776 drugged rats doing better then non-medicated rats, yet still worse then the rats with no TBI, which is to be expected.
The 3 categories of rats were then put through a test of motor skills. This was done through a swim test. Interestingly enough the two groups that suffered a TBI did best in the swim test with the TBI + PGI-02776 group swimming the fastest. I don’t know what to make of this data and it seems neither did the research group, they didn’t touch on the subject after writing the results.
Take home messages?
It seems that there may be solutions to concussions in the future. But this research must also be taken with not a grain but a large chunk of salt, just because something works in rats doesn’t mean it will work in humans to the same extent. Also this research is really only focused on the positive outcomes it isn’t known what side effects with come from PGI-02776 in the human body.
(1) Feng, J.; Van, K. C.; Gurkoff, G. G.; Kopriva, C.; Olszewski, R. T.; Song, M.; Sun, S.; Xu, M.; Neale, J. H.; Yuen, P.; Lowe, D. A.; Zhou, J.; Lyeth, B. G. Post-injury administration of NAAG peptidase inhibitor prodrug, PGI-02776, in experimental TBI. Brain Res. 2011, 1395, 62-73.
What happens when you get knocked on the head?
One of the most current and serious health issues today is concussion. You hear about it everywhere from the 4th grade football game to the scene of a fender bender. One of the scariest things about concussion is that it manifests itself in so many different ways– what exactly constitutes a concussion? Does everyone who has a concussion go unconscious? How long until your injury will heal? These questions are nearly impossible to answer because you are dealing with different bodies and different injuries.
3
According to the CDC, 1.7 million people suffer from concussions each year.1 Furthermore, they are the cause of 1/3 of all injury-related deaths annually.1 Sports-related concussions are particularly alarming due to their prevalence among adolescents. Per year, it is estimated that 1.6-3.8 million sports related concussions occur in the U.S. to those between the ages of 5 and 18.2 Frighteningly, some hypothesize that at least one mild concussion occurs in every football game played in the U.S.2 While many know that concussions are serious brain injuries, most are still unaware of the biology and chemistry behind these injuries.
What happens?
When the brain goes through some mechanical impact, the first thing that occurs is the opening of K+ channels. Since the cell usually maintains a negative charge within the cell and a positive charge outside the cell, this forces Na+/K+ pumps, the ones which move Na+ out and K+ in, to work overtime.
These channels working overtime is bad news for the cell. The pump needs energy to run, so this forces the cell to try to produce more and more ATP through glycolysis. However, since the brain is always running at its max energy production, this just causes stress on the cell. Additionally, since blood flow decreases in the brain upon injury, the cell doesn’t have much glucose to use to make ATP. Lactate, the endproduct of glycolysis, accumulates in the cell causing swelling and other adverse effects.
Another issue which the mechanical force causes is excitatory neurotransmitter release. Glutamate, the most common excitatory neurotransmitter, binds to its receptors which cause increased Ca2+ levels in the cell. Since Ca2+ in the cell is necessary for neurotransmitter release, this causes further excitation and release of glutamate. Increased Ca2+ also impairs mitochondria, the major players in oxidative metabolism. Of course, this just adds to the decreased energy problem the cell has. Lastly, another imbalance occurs within the cell – lowered Mg2+ levels. This has widespread effects for the cell as Mg2+ is required for so many cellular functions. One of these is energy production.4
The basic story of concussion seems to be a blow to the head and a resulting imbalance of ions and excitation. This leaves your cell scrambling to put everything back in its proper place, which requires a lot of energy – in fact, more energy than the cell can provide in its injured state. Hopefully someday we can find a better way to protect our brains from being knocked around so much, or possibly a chemical treatment to help the cell effectively restore its original balances.
1. http://www.cdc.gov/traumaticbraininjury/
2. http://www.momsteam.com/health-safety/concussion-rates-high-school-sports
3. http://www.womensradio.com/articles/Brain-Injuries%3A-Something-Soldiers-and-Athletes-Have-In-Common/1948.html
4. Giza CC, Hovda DA. The neurometabolic cascade of concussion. Journal of Athletic Training 2001; 36(3): 228-235.