Do you ever crave food to the point where you are pretty sure you are addicted? Well, turns out you might actually be addicted to food. Recent studies have connected obesity and overeating to changes that manifest in the brain, specifically linked to energy homeostasis which is the balance of energy in your body. The hypothalamus in your brain is what maintains this homeostasis by regulating feeding behavior and energy expenditure, in other words when you eat and when you exercise is controlled by the hypothalamus. You may be questioning how your brain knows what the rest of your body needs, well this is through insulin and leptin signaling. Insulin and leptin begin signal cascades that lead to the response “stop eating and expend energy.”

Leptin is a hormone produced by adipocytes, fat cells, and binds to receptors in the hypothalamus. The receptor then begins a signal cascade that activates the synthesis of the neuropeptides proopiomelanocortin (POMC) and cocaine and amphetamine regulated transcription (CART). These neuropeptides then lead to the “stop eating and expend energy” response. The leptin signal cascade also results in the inhibition of agouti-related peptide (AgRP) and neuropeptide Y (NPY) which are neuropeptides that signal the “eat now” response. This is great, because it tells your body you’re full. You have enough energy to do life. But there’s a catch! FOXO1 inhibits the action of this signaling cascade leading to the opposite response, “eat more.” To combat this, insulin steps in.

Insulin is a hormone produced in the pancreas, that also binds to receptors in the hypothalamus. Insulin initiates a signal cascade that kicks FOXO1 out of the nucleus so it can’t disrupt the leptin signaling. The figure below shows how leptin and insulin control appetite in the hypothalamus.

If there is a lack of leptin or insulin, POMC and CART will not be synthesized to give the “stop eating and expend energy” response. The figure also shows that ghrelin, produced in the stomach will also induce appetite. AgRP and NPY will be synthesized leading to the “eat now” response. If you haven’t eaten for a while and need some energy this is good. But, if this signal occurs even when you’re not hungry, then you have a problem. This uncoupling of the “eat now” response and the amount of energy one has is key in obesity.

So, how does this signal happen when you don’t need energy? Obesity leads to this disruption of energy signaling in a number of ways. One way is that a high fat diet causes the activation of inflammation in the hypothalamus which elicits a stress response from the endoplasmic reticulum (ER). ER stress leads to leptin and insulin resistance, therefore increasing AgRP and NPY neuropeptides and the “eat now” response. The body still produces leptin and insulin, but now the hypothalamus can’t send out the correct signal. This leads to overeating because an individual will continue to eat after attaining their energy threshold. In mice, the hypothalamus returned to its normal size after three days on a low-fat diet. So, no worries, one meal won’t send you down an uncontrollable food tunnel. However, prolonged high fat diets could lead to the uncoupling of energy need and feeding behavior. Therefore, proper nutrition and portions is key to maintaining a healthy lifestyle.

In America, it seems that athletics is just as stressed, if not more than, as academics. We live in a culture where professional athletes are praised and put in the spotlight, and the pressure put on them to perform no matter the circumstances is extremely high. So, despite dangerous injuries, professional athletes would often stay in the game to prove their “toughness,” and that tended to be the expectation from coaches since the inception of athletic events. Unfortunately, high school athletes who would follow professional athletes would take cue from them and buy into the idea that they should play at all costs. For specific injuries like concussions, which we now know are extremely dangerous and serious, one important question to ask is why do many high school athletes not report the symptoms of concussion?

Just a Few Reasons

1. Winning at all costs

High school athletics are important and are most often extremely beneficial to kids with regards to social connections, teaching discipline, and learning vital teamwork skills. However, far too often are high school athletics not kept in perspective.

When asked in a study that was published by the Journal of Athletic Training, up to 55% of high school athletes reported that they didn’t or wouldn’t report a concussion. A strong argument could be made that one contributing factor is the athletes did not want to sacrifice playing time to protect their physical health. They are taken too seriously, specifically when it comes to athletes’ injuries.

    2. “I can’t let my team or coach down”

Although a noble motivation, putting the team or opinion of the coach ahead of one’s physical health is extremely risky. Many athletes feel myriad emotions when it comes to physical injuries, and a common one is that they believe they will look “weak” if they complain of pain. According to an article by Reuters Health, males especially tend to be more sensitive to how their fellow teammates and coaches view them. This is arguably due to the expectation that men are supposed to be strong and resilient, and showing emotion is can be considered a “vulnerability” in the sports realm.

   3. Honest Ignorance

At higher levels of athletics like college and professional sports, the signs and symptoms of concussions are well known and monitored at the slightest instance of a hit to the head.

However, in high school athletics, strict regulations like that of college and professional sports are not uniformly enforced. This leads to high numbers of ill-informed or uninformed high school athletes and coaching staffs. Not knowing the symptoms of a concussion is dangerous, and too many kids have stated that they did not know they had a concussion while they were concussed.

The Solutions

One solution to these problems first and foremost is education. Coaches need to understand the seriousness of concussions and the lasting effects they can have, like difficulty concentrating, personality changes, difficulty with memory, and many more. These are exacerbated if and when someone sustains a second concussion, which is easier to obtain having had an initial concussion. Another point of importance to be stressed to high school athletes, parents of athletes, and coaching staffs is: keep athletics in perspective. Sacrificing enduring brain health problems for a game is never the answer. Brain injuries are unlike injuries to other parts of the body, and injuries to the brain must be treated accordingly. Not to diminish the importance and amazing accomplishments to be had in high school athletics, but after all, it is just a game.

The Science

Many things have been studied that occur after a significant impact to the head is sustained. After impact, potassium flows out of the cell while sodium and calcium flows into the cell, and this is allowed because of defects in lipid membranes that occur after the trauma. This causes an ion flux and a subsequent depolarization that can lead to depression-like responses that are attributed to the post-concussive impairments. To combat this, ionic pumps that require ATP are overactive, which leads to hyperglycolysis. This results in an imbalanced energy supply and demand, which ultimately leads to a variety of metabolic changes that are serious to say the least. The force of an impact can also damage the cytoskeletal structures like dendritic arbors, axons, and astrocytic processes. This often leads to the loss of integrity of axons, and in extreme cases axonal disconnection occurs. Overall, it is not just one specific thing that can be pinpointed when determining the cause for a concussion but rather many things that can and do contribute to the effects of a concussion.

CONCUSSIONS are one of the most commonly encountered sports injuries where rates are estimated at two million sport related concussions per year in the United States according to the Brain Injury Research Institute. This number is potentially much larger due to the lack of knowledge and awareness about concussion and brain injuries. There has been an increase in research attempting to understand what happens in the concussed brain, but there is a long way to go to help identify treatment plans and return to play protocols. For now, we maybe shouldn’t listen to Zac Efron and his High School Musical buddies. So let’s keep our head out of the game and, instead, focus on raising awareness about concussions and other injuries to the brain.

A vast array of symptoms that can be associated with concussions and traumatic brain injuries (TBI) are a result of the diversity and broadness of factors relating to basic neurobiology and a neurometabolic cascade. These factors include ionic flux and glutamate release, energy crisis, cytoskeletal damage, axonal dysfunction and altered neurotransmission, and inflammation.

IONIC FLUX AND GLUTAMATE RELEASE

Upon a biomechanical injury, potassium efflux and sodium and calcium influx occur due to a damaged phospholipid membrane. An efficient action potential will not be able to be produced because of abnormal depolarization from the rapid influx of sodium and calcium.

ENERGY CRISIS

In an effort to maintain cellular homeostasis regarding ionic flux, ionic pumps that require ATP are shifted into overdrive. This leads to a depletion of energy reserves, thus resulting in reduced cerebral blood flow and an imbalance between energy supply and demand. Prolonged calcium influx leads to increased intracellular calcium and greater amounts of calcium to be sequestered in the mitochondria. Too much sequestration can result in mitochondrial dysfunction which causes the energy crisis.

CYTOSKELETAL DAMAGE

The cytoskeletal structure which include microtubules and microfilaments consist of delicate and complex components. When damage is implemented to a brain region, neurofilaments can easily be phosphorylated and break. Axonal influx of calcium results in the breakdown of proteins into smaller polypeptides on cytoskeletal components. This damage makes the neurons more prone to axonal disconnection and death. After a TBI, ongoing cerebral and hippocampal atrophy may be present. The progressive atrophy can show the appearance of cognitive deficits later in life. The occurrence of a TBI before full recovery from a previous TBI may more likely trigger activation of intracellular proteases and the cascade that leads to apoptotic cell death.

AXONAL DYSFUNCTION AND ALTERED NEUROTRANSMISSION

Increased axonal permeability after a TBI is a result of the vulnerability of the axon. Consequently, this can lead to overall axonal dysfunction. A damaged neuron where neurofilaments and microtubules are altered allows for the neuron to not normally function. Injury to the axon and other white matter areas occurs along with mechanoporation, stretching of individual axons, disruption of axonal transport, axonal misshaping, and axonal disconnection.

Altered neuronal transmission is present after a TBI and occurs due to an imbalance in excitatory and inhibitory neurotransmission. This imbalance is seen due to alterations in the glutamate receptors or GABA receptors which alter excitation and inhibition. Alterations in glutamate, an excitatory neurotransmitter, affect the normal functions of calcium flux and the activation of downstream signal transduction molecules. Decreased levels of GABA, an inhibitory neurotransmitter, affect fear-based learning associated in the amygdala.

INFLAMMATION

Changes in inflammatory markers following a TBI has shown an activation of microglia in the cortex. Microglia function as macrophages in the central nervous system to mediate immune responses. Upon damage to the brain, inflammatory changes are triggered by the upregulation of cytokine and inflammatory genes. Inflammation, although an evolutionary mechanism for protection, has also been shown to induce damage to brain regions that relate to long term side effects. For example, microglial response to damage in the substantia nigra has been shown to increase risk of Parkinson’s Disease after a TBI.

WHY IS THIS SO IMPORTANT?

The research presented above sheds light onto why there are so many symptoms involved with brain injury and concussion. A list of symptoms is listed below:

• Migraine headache
• Photophobia and phonophobia
• Vulnerability to second injury
• Impaired cognition
• Slowed processing and slowed reaction time
• Chronic atrophy
• Development of persistent impairments

Concussions affect each individual differently and symptoms depend on a number of factors including strength of trauma and the brain area affected by the trauma. When an individual is experiencing these symptoms, they must be monitored closely. Both physical and mental rest can speed the recovery of concussions. Unfortunately, there is still much more research to better understand how to prevent concussions and the symptoms associated with them.

CONCUSSIONS and any injury to the brain are not to be taken lightly. The broadness of symptoms associated can have long term affects. Management of concussions will continue to evolve as more research develops. This will allow us to better understand the steps toward prevention, treatment, and return to play protocols. Protection of athletes and all those more prone to concussion is the number one priority. If you are experiencing any of the concussion symptoms talk to a health professional and play it safe by getting your head out of the game!

For more information on the research presented, follow:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479139/

For more information on the symptoms associated with concussion, follow:

https://www.mayoclinic.org/diseases-conditions/concussion/symptoms-causes/syc-20355594

It’s simple logic. As with anything else in the body, if your brain is hurt (in an injury such as a concussion), give it a rest. The concept itself seems easy enough to grasp. Given how important the brain is, why would anyone even bother second guessing the time it takes for the brain to rest and recover? Nonetheless, you’ve probably known (or maybe you are) someone who’s brushed off a head injury as a “minor incident” or who’s been reluctant to let a concussion keep them from participating in athletics. The Return-to-Play rules governing concussed athletes are relentlessly stringent, and it’s certainly frustrating to be kept off the court by what many young athletes consider a “pounding headache.” But they are there for a reason. We often are familiar with the immediate affects of suffering a concussion, but what actually goes on up there when the brain is hit with a sudden force? And with ugly truths emerging in recent NFL brain injury studies, what devastating long-term impacts can result from a single blow to the head?

What’s the Fuss Behind the Concussed?

Before we discuss the concussed, some of you might be wondering: what exactly is a concussion? The CDC defines a concussion as “a type of traumatic brain injury—or TBI—caused by a bump, blow, or jolt to the head or by a hit to the body that causes the head and brain to move rapidly back and forth.” It is this sudden motion that can damage the brain and its cells, causing the symptoms we are all too familiar with. We are well aware of what happens during an immediate concussion. Vision gets blurry, memory gets fuzzy, and speech gets slurred. If you are not yet aware, some of the common post-concussion symptoms are:

• Dizziness
• Fatigue
• Anxiety
• Headache
• Sensitivity to light and sound
• Loss of concentration and memory
• Confusion
• Low energy levels, irritability, sleep problems

For a full list of symptoms and more about concussions, visit the Mayo Clinic page here.

But what about a child’s long term health? Many parents of young athletes are familiar with the importance of proper brain development throughout childhood and in the teen years. Recent studies indicate that although long term amnesia or cognitive declines are rare in those who have suffered a concussion, if enough brain damage is sustained (for example, obtaining a second concussion while still recovering from a first) the outcomes can be dire. Long term deficits, such as

• CTE (chronic traumatic encephalopathy, caused by repeated head injury, which can display as the below symptoms)
• Alzheimer’s-like memory loss
• Cognitive decline

might occur in patients when they grow older. A shocking statistic? In a study done on 111 brains of post-mortem NFL players, 110 had CTE – which really sheds the light on just how serious a “simple concussion” can turn out to be. Next, let’s look at the science that actually causes these symptoms and underlies a concussion.

[A concussion is] a type of traumatic brain injury—or TBI—caused by a bump, blow, or jolt to the head or by a hit to the body that causes the head and brain to move rapidly back and forth.

Heads up – What’s Going on Up There?

So, a ball slams into the head, and the brain jolts. What next? The steps that occur in the brain following blunt impact can be summarized as follows:

• Impact stretches cell membranes of brain cells (neurons and supporting cells), damaging them and making the membranes porous
• Chemical gradient disrupted due to pores (K+ out and Na+ in), causing unintentional depolarizations and irregular action potentials.
• Irregular action potentials lead to release of neurotransmitters in a neuron, especially glutamate (a major excitatory neurotransmitter in the brain), and neurotransmitter imbalance results
• Glutamate binds to a molecule, called an NMDA receptor, on the downstream neuron.
• Together, the depolarization and the glutamate binding opens NMDAr, which allows calcium to enter the neuron.
  • This overabundance of Ca2+ can set off a variety of chemical cascades. In concussions, it mainly affects the mitochondrion (yes, the “powerhouse of the cell”)
• In an attempt to reset the chemical imbalance between K+ and Na+, a molecule “pump” called an ATPase pumps out 3 Na+ for 2 K+ in. This requires a form of “energy currency,” called ATP, the “power” generated by the mitochondrion.
  • The mitochondria work harder to produce more ATP to power this process
  • In doing so, the mitochondria deplete energy stores and use too much glycogen
  • This causes a state known as “hyperglycolysis,” where too much glycogen is broken down (why concussed patients are often “tired”
  • This is also a supply demand problem – during a concussion, there’s decreased blood flow to the brain
    • Less blood means less oxygen to the brain, so the mitochondria must rely on anaerobic respiration, generating harmful lactic acid
  • The mitochondria also try to contain some of the excess Ca2+ in the meantime
  • Bottom line: Mitochondria are overstressed, overworked, and underpaid.

Why is this so detrimental? The ability of a neuron to fire depends on the maintenance of a chemical gradient and ability to send action potentials, which is the means by which neurons communicate. If the chemical gradient of Na+ and K+ is disrupted, as described previously, neurons might struggle to fire, leading to problems in brain function and some of the immediate symptoms listed previously.

In the long term, these overworked, stressed mitochondria produce less ATP than they’d normally be able to. This chronic low-level energy lasts for a while and throughout most of the concussion recovery process, leading to low metabolism and low energy levels as the brain tries to recover. The lactic acid produced (the same stuff that makes your muscles sore after a workout) also might make brain conditions overly acidic (acidosis), which can further prevent chemical gradients from re-establishing, denature/damage proteins, and altogether cause more brain damage. Ultimately, this imbalance can cause structural damage to filaments and other elements of brain cells, and ultimately cell death or “apoptosis” (programmed cell death).

In the case of repeated head injuries and conditions such as CTE, imagine this entire process happening again while the brain is still trying to recover. It is this combination of events that leads the brain to a point where it literally cannot recover – causing long term brain damage.

So what can we do to keep young athletes from suffering brain injuries? We can’t just tell everyone to stop playing football (or any other sport, for that matter). Because concussions have become so relevant in modern day athletics, recent research has gone into developing better gear (such as football helmets) that can reduce, mitigate, or detect the amount of impact a player is receiving. Some prototypic helmets even have impact sensors that can indicate how much force the brain has received, so players can be pulled out when the limit is reached! Moving beyond athletics, technology is constantly being developed to reduce impact during car crashes, accidents, and other potential TBI-inducing situations.

So what do we gain from all this? Hopefully less minor brain injury for our future youth athletes. At the end of the day, the brain is incredibly complex, and this pink, wrinkly organ holds the key to one’s limitless thought and action. But the brain does have its own limits – the brain is just as delicate as it is complex and crucial for one’s survival. At the end of the day, it’s important to recognize when to pull your head out of the game and let the brain work its own magic.