Cobbers on the Brain – Page 56 – Student Commentary on the Neurological Sciences

Rapamycin: Potentially the answer to Alzheimers – and Aging?

Posted on October 28, 2020 by / 0 Comment

Most everyone has heard of Alzheimer’s Disease, far too often because of personal experience with loved ones. Although everyone associates the disease with someone losing their memory (and rightfully so), a physiological hallmark of Alzheimers is insulin resistance, which is thought of as the state of not having enough insulin, for one reason or another.

Insulin is most commonly known for its role in regulating metabolism. Insulin however, does a whole host of other helpful things for our bodies, including the regulation of synaptic plasticity, being neuroprotective, acting on neuronal growth and survival, and has been proposed to regulate the gene expression required for the ability to consolidate long term memories. All of this alludes to the fact that if we don’t have enough insulin, as seen in Alzheimers, we have a problem.

What can we do?

Insulin resistance has been observed to occur due to an inhibited insulin signalling pathway and an overactive pathway that leads that resistance called mTOR1 (mammalian target of rapamycin). However, with a drug called Rapamycin, mTOR can be inhibited and insulin resistance is abolished. Now, this doesn’t solve Alzheimers, but it’s certainly a step in the right direction for treatment if nothing else.

Some researchers however are suggesting that rapamycin has additional beneficial effects than simply increasing insulin (although this still might be the mechanism, the benefits are broader than simply treating Alzheimers). One of the positive effects of rapamycin that was found was that, when intermittently administered, rapamycin led to stem cell regeneration. Considering some of the applications for stem cells, this is an amazing discovery that could have far reaching implications on the future of medicine. And that’s potentially just the tip of the iceberg. Because of the mTOR1 inhibition through rapamycin, it has been found that there is a decreased risk of cancer, since mTOR1 signaling can lead to cell proliferation. Tumor regression has also been observed to occur. It’s also been found that mTOR1 signalling sometimes leads to misfolded proteins. Using rapamycin, inhibiting mTOR1 led to greater autophagy and suppression of protein synthesis, which is important because this means that rapamycin can have neuroprotective effects in not just Alzheimers, but also Parkinson’s Disease and Huntington’s Disease.

One of the most interesting positive effects found from administration of rapamycin was its ability to increase the lifespan of rats that were treated with the drug. It does this through slowing down the aging process along with inhibiting metabolic or neoplastic diseases. This also potentially includes cancer, as regulating cell proliferation through the drug means that cancer cells can’t spread as rapidly, and cancer cells may also happen less in the first place.

Before we all start taking insulin, it’s important to remember however that one of the most consequential aspects of a drug’s effects and effectiveness is the dosage and how often its administration. With rapamycin, the appropriate ratios of both of these factors are still unknown as of yet, but research is being done to try decipher further how to access the perceived positive effects of the drug. It has been seen though that rapamycin doesn’t fully inhibit mTORC1 processes, and so a combination with another treatment would more effectively implement the positive effects of Rapamycin.

This being said, there are observed downsides, which shouldn’t ever be overlooked within any kind of drug treatment. Rapamycin has been sometimes seen to actually increase insulin resistance, but the mechanism for why this occurs is speculated to be known (inhibition of mTOR2). Other negative effects included increased hyperglycemia within type 2 diabetes mouse models, and the ability for tumors to start regrowing after treatment with rapamycin stopped.

To end on a positive note about rapamycin treatment, there are no known overdose deaths due, which could signify that the ability for researchers to manipulate administered dosage levels could be rather high. All in all, more research into the side-effects and anti-aging effects of rapamycin are needed, but some people even now think that rapamycin can be used as an effective anti-aging (or at least an anti-disease) drug with very few discovered side-effects.

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Knocking Out Concussions: What do Concussions Mean for Athletes?

Posted on October 27, 2020 by / 0 Comment

Imagine you are at a high school football game. The tension in the air is thick as the play is ran, and you see a player that is hit, who falls down to the ground with a thud and doesn’t get back up right away. Generally, a medic/trainer will run out to the field and complete an assessment of the player to make sure they’re physically okay and check for a possible concussion. The player gets back up, shakes it off, and keeps playing. Do you think about it anymore after that? Concussions, or mild traumatic brain injuries (mTBIs), don’t necessarily always have to be symptomatic concussions or knock out the person, but they can put someone at an elevated risk of future concussions and can result in long-term impairments.

What are Concussions?

When we think of concussions, we tend to think of a hard hit to the head, one that may make you dizzy or confused, maybe even knock you unconscious. There’s a lot more that goes on though during a concussion than most people realize, and it’s important to know what is going on during a concussion to recognize the signs of one. A concussion, or mTBI, occurs when there is a significant blow or hit to the head that causes the brain to bruise, and rebound off the other side of the skull; this rebounding is referred to as the contrecoup. This rattling of the brain can disrupt axons and rupture the blood vessels. After a concussion occurs, the person may experience a variety of symptoms. They may have any of the following: headaches, confusion, dizziness, memory loss, nausea, blurred vision, sensitivity to noise and light, sleeping disturbances, mood changes, especially irritability, and may display slurred speech. To read more on the types of symptoms, you can read here: https://www.mayoclinic.org/diseases-conditions/concussion/symptoms-causes/syc-20355594

A concussion does not always create these symptoms though. People can also undergo sub-concussive impacts, which are blows to the head that do not cause full concussions. These types of hits can be incredibly dangerous because the person who has been hit may think they are fine because they have no symptoms, but the impact is putting them at a very high risk of developing a full concussion.

Inside the Brain

Now that we know what is occurring symptomatically during a full concussion, what is happening in the pathophysiology of the brain to result in these impairments? When a mTBI occurs, a neurometabolic cascade occurs. In the initial stages of the cascade, an ionic flux and depolarization occurs, which triggers excitatory neurotransmitters like glutamate to be released. There are ATP-ionic pumps within the membrane that are overstimulated due to this and creates an increase in ADP, an efflux of potassium, hyperglycolysis, and an influx of calcium. This creates an imbalance, or energy crisis. The imbalance ultimately leads to damage of axonal integrity, mitochondrial dysfunction, and altered neurotransmission. It’s also important to note the role of inflammation after a mTBI. Microglia are activated after a blow to the head, stimulating upregulation of cytokine, and ultimately activating inflammatory genes. Inflammation can result in severe headaches, or even rupturing blood vessels in the brain. Due to these pathophysiology changes that occur from a mTBI, long-term structural changes can occur within the brain and result in atrophy.

Looking Forward

Researching concussions has become a hotspot in the neuroscience community due to the prevalence it has in the sport world. Many athletes in contact sports like football, boxing, or hockey experience multiple concussions within their life and can suffer from long-term, symptomatic impairments that affect their everyday life. There are many athletes who have received so many hits to the head, especially boxers, that are at an elevated risk of developing chronic traumatic encephalopathy (CTE), which is a progressive neurodegenerative disease. CTE develops after years of repetitive symptomatic concussions and sub-concussive impacts and tends to cause severe memory loss, confusion, impulsivity, depression, and aggression. It’s important to be researching concussions to possible prevent CTE or multiple concussions from occurring. Young athletes are especially vulnerable to this due to the brain’s development, which means at a younger age there are more unmyelinated axons that are vulnerable to injury. With so many young people participating in sports and being placed at a higher risk of developing a concussion, society needs to look at different preventative measures that can be put into place to try and fully prevent mTBIs, or curb the progression to CTE.

References:

https://www.pearson.com/us/higher-education/product/Carlson-Physiology-of-Behavior-12th-Edition/9780134080918.html

https://www.bu.edu/cte/about/frequently-asked-questions/#:~:text=Chronic%20Traumatic%20Encephalopathy%20(CTE)%20is,that%20do%20not%20cause%20symptoms.

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The Joy of Winter Football Games

Posted on October 27, 2020 by / 0 Comment

The snap-crunch of football pads & helmets colliding pulled my attention up from wrapping yet another blanket around myself as I watched my younger brother’s third high school football game of the COVID-modified season while sitting in cold, snow-covered, and socially distanced bleachers with about 30 other player family members. It was 19 degrees Fahrenheit. I was sitting on an inflatable camping sleeping pad with my mom as 22 high school students ran around the field in front of us, each student using the exercise as a somewhat futile attempt to stay warm while endeavoring valiantly to score more points than the other team. Yet, as these athletes gave all of their attention to the game, my mind as a scientist and concerned sibling was drawn to one of the physical perils of competitive varsity football: concussions. As my brother is the star first-string outside linebacker and running back of his team, he ends up involved in tackles on either the receiving or performing side of things on nearly every play.

Concussions are an insidiously common type of mild traumatic brain injury (mTBI) that occurs when the brain rapidly moves within the skull as the head is subjected to rapid acceleration and deceleration. For example – during a football tackle. While advances in protective technology for athletes helps reduce risk, the risk is never zero. This injury can result in both immediate symptoms – pain, ‘seeing stars,’ confusion, headaches – and symptoms lasting weeks – headaches, confusion, and inability to focus. This begs the question, what is happening on a fundamental biochemical level to cause these symptoms?

Inside the brain

Once the initial impact causing the concussion occurs, a cascade of events altering the chemical balance in the brain takes place. First, instead of the typical highly regulated signaling expected in a normal functioning brain, nonspecific depolarization and initiation of axon potentials occur. This causes the release of excitatory neurotransmitters to be widely released throughout the brain at a scale not seen under normal circumstances. This leads to the efflux of potassium ions from the brain and severe ion imbalance, leading to extremely high activity of ATPase, an enzyme responsible for maintaining ion balance in neurons. Since ATPase is powered by ATP, the brain enters an energy crisis trying to restore the ion balance and burns through stored glucose reserves to meet the need. When glucose runs out, the brain switches to other sources of energy which causes lactate to accumulate in the brain. At the same time, the physical injury to neurons results in Calcium entry into the cells. While the ATPase will help rebalance the Calcium entry eventually, in the short-term Calcium entry results in sequestration in the mitochondria. This Calcium imbalance both impairs the mitochondria’s ability to be the “powerhouse of the cell” by interfering with ATP production, further contributing to the brain’s energy crisis, but too much Calcium activates calpain proteins which then initiate apoptosis, or programmed cell death, which results in the dying back of neurons in concussed areas.

Image source: Giza, C. C., & Hovda, D. A. (2001). The Neurometabolic Cascade of Concussion. Journal of Athletic Training, 36(3), 228–235.

Additionally, scientists are building on this understanding of what happens in concussion by looking at what small chemical messengers that modulate inflammatory responses called cytokines do to change inflammation states in response to injury. After the injury, glial cells called microglia and astrocytes become activated and produce Glial Fibrillary Acidic Protein (GFAP, a biomarker of brain injury) and both pro- and anti-inflammatory cytokines. Due to the existence of both pro- and anti-inflammatory cytokines, teasing apart the differences in how these factors change inflammatory responses is pretty challenging. Interleukin 1 beta (IL-1b) offers an excellent case study in the challenges and opportunities presented by cytokine study.

IL-1b expression patterns after injury show a gradual rise in expression levels, with expression levels directly correlating with the severity of the injury. Interestingly, IL-1b causes the release of ciliary neurotrophic factor (CTNF) and nerve growth factor (NGF), two hormones associated with recovery from concussion. However, IL-1b also stimulates the release of high levels of other inflammation-causing cytokines such as tumor necrosis factor-alpha (TNF-a), which results in toxic inflammation. Therefore, some suggest that interrupting IL-1b after it stimulates growth factor release but before it can stimulate pro-inflammatory cascades may be an effective therapeutic target. Cytokines are incredibly important in regulating neuroinflammation and have both anti- and pro-inflammatory properties, therefore, parsing apart the exact cytokines associated with triggering hyperinflammatory cascades and interrupting their signaling cascades could serve as a therapeutic target in the treatment of concussion.

Clearly, a pharmacologic intervention for concussion treatment is still years away from becoming a reality for athletes. Currently, the best ‘treatment’ for concussions is prevention through educating players, coaches, and parents of all sports on methods that minimize risks of getting a concussion such as proper tackling and running technique, as expertly demonstrated by my brother in his game. While my brother’s team narrowly lost on Friday night, no player got a concussion. So, while not as immediately satisfying as a win, I take solace in the knowledge that through coaching and mentorship, everyone walked away safely.

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Concussions and Tau: The Danger You Might Not See

Posted on October 27, 2020 by / 0 Comment

Well, this began as a foray into concussions and the damage that is caused behind the scenes. Now as an athlete myself, I understand the danger of concussions and know that proper handling of any type of brain injury is vital to the continued function of that brain as we know it. That’s why the direction my research took me began to scare me. As I looked more into the effects sub-concussive impacts, I began to see more ties and connections to various terminal diseases. At this point in time, to nobody’s surprise, I found CTE as a linked disease associated with this repeated trauma. But what I had not expected was that even “non-traumatic” contacts led to a connection to Alzheimer’s. Alzheimer’s is typically characterized by tau accumulations (which can lead to Neurofibrillary tangles) and β Amyloid plaques.

To skip a lot of nuance, a concussion occurs when axonal damage is inflicted. This axonal damage leads to what is called a “Neurometabolic Cascade”, which causes axons and their function to go haywire. One such issue begins with ion flux in a neuron, and results in the spreading of a depression-like state. There is the beginning of an energy imbalance, and ultimately causes mitochondrial dysfunction, and metabolism changes that are associated with losses in the ability to learn. Of course, these are important, and concussions are typically very closely monitored. What is often overlooked however, is the sub-concussive impacts. These sub-concussive hits will not damage axons, however they will damage the even more fragile microtubules, which in turn releases bits of it’s structural protein, tau. For the most part this tau is soluble, but where the problems occur is under certain situations, the tau can be phosphorylated, and form clumps which are now insoluble. As most could probably guess, this is most commonly seen in boxers. Shocker! However newer research is seeing the changes in tau levels in college athletes as well, and have seen a correlation between tau levels and the return to play time! At 6 hours after the injury, or the SRC (Sports Related Concussion), if an athlete’s plasma tau levels were above the threshold, it was consistent with a >10 day Return To Play protocol, whereas those who were under the threshold had an RTP of 3-5 days. While the biomarkers are monitored it is important to note that the RTP is still symptom based.

Where I am conflicted, is in my belief that this is a good thing for athletes. It is great we are seeing biomarkers, especially those which can be found in blood plasma and gathered relatively un-invasively. But that biomarker we are seeing we know is due to some sort of damage to the brain. Damage that releases a protein we can link directly to Alzheimer’s as well as CTE. While this may lead to an improvement in treatment, it is by no means a method of prevention.

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The Hidden Hinderance of Bilingualism

Posted on October 27, 2020 by / 0 Comment

As communities continue to be more and more diverse in their populations, the number of languages present increases as well. As bilingualism becomes more common in households across the world, the benefits of such a skill of knowing more than one language has come into question.

There is a theory, typically called the “critical period hypothesis” that states that children have an easier time learning and better benefit from learning a second language in comparison to adults. This theory follows the stereotypical generalization that the left brain is the “logical and analytical” side of the brain, whereas the right brain is considered to be “emotional and creative.” Though this has been disproven and is no longer a well-held theory in psychology and neuroscience, you still see it from time to time in generalizable situations.

For example, the “critical period hypothesis” states that children get more out of learning a second language because their brains are still developing, and synaptic plasticity is at a high. This is believed to allow children to learn the language on both sides of the brain and gain an emotional component to the language, where adults are believed to lean more towards a “left-brain” understanding of the language.

This learning of a second language tends to be localized to the dorsolateral prefrontal cortex which is also highly involved in executive functioning, such as working memory and flexible thinking. The learning of a second language is believed to strengthen executive function, and in turn be a neuroprotective factor of neurogenerative diseases, such as Alzheimer’s and dementia.

Though the idea of teaching a child a second language seems like a simple “YES” answer, there is a secret hinderance that has come into the light of research. With 1.4 million individuals experiencing a mild traumatic brain injury (mTBI) on a yearly basis with most occurring in the prefrontal cortex or temporal lobes, it definitely raises the question if bilingualism still shows similar neuroprotective factors.

According to Raitu et al. (2017), a bilingual brain is just as susceptible to the impaired executive function and cognition as any monolingual brain. Even if the neurons are strengthened by the bilingual brain they still undergo immense strain following an mTBI. This strain comes from the calcium influx, axonal injury, altered neurotransmission, and vulnerability to second injury from an energy metabolism crisis. Specifically, axonal injury and altered neurotransmission is believed to be at the root of impaired cognition and executive function following an mTBI.

Besides being just as susceptible to executive function deficits, bilinguals are also at an increase risk of language control deficits following a mTBI. One theory states that following a mTBI, languages return in a disproportionate manner with the one most frequently used at time of impact returns faster. Monolinguals sustaining one mTBI have not been mentioned to experience such a deficit.

This language control deficit coming from axonal injury raises a concern from the lack of myelination seen in younger children. Myelination offers a “cushion” to the axon, and a decreased volume of myelin on any neuronal axon can significantly impact the results of an mTBI.

To put it all together, if a child learns a second language during the critical period of development, it can significantly benefit them in the long run. However, they are at an increased risk of executive function and language control deficits after sustaining an mTBI, or concussion, due to lack of myelination on axons in their developing brain. This can impact the recovery time and “Return to Play/Learn”. This is not meant to discourage bilingualism, but to show how important it is to take head injuries seriously in children with their developing brain.

Photo Sourced From: https://mosaicscience.com/bilingual-brains/

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Concussion: CBD as a Potential Treatment?

Posted on October 27, 2020 by / 0 Comment

Concussions, AKA mild traumatic brain injuries (mTBIs), can be frustrating to deal with. This is because they can cause many side effects including: headaches, confusion, nausea, depression, amnesia, trouble sleeping, and difficulty with concentration and learning. Although the symptoms usually disappear after a few weeks, as the brain heals, during the concussion one must put their life on hold. This is because the only current treatment for concussions is getting plenty of physical and mental rest. Along with over-the-counter medications, to make the person comfortable and alleviate headaches. This leads to the question, are there other medications that could be taken to help after a concussion?

In The Brain

First, it is important to understand what is happening in the brain when someone gets a concussion. When the brain gets shook around in the skull there can be injuries to axons which is a part of a neuron. Neurons are cells that send signals to one another which allows us to function. The axons could be bent, broken, or dead due to impact. The impact causes a leaky membrane on the neuron. This causes ions like calcium and sodium to come into the axon, allowing the neuron to become imbalanced and depolarized. Depolarization is important because when a neuron becomes depolarized it has more positive ions, which makes the neuron altogether more positive. A positively charged neuron wants to signal to other neurons.

After depolarization, the living, damaged neurons will then over signal causing glutamate release. Glutamate is a neurotransmitter that travels to other neurons making them fire. All of this firing causing a lot of activity to happen in the brain. The brain knows that the ions are not balanced, so it will use a lot of sodium, potassium, and ATP to try to balance out these ions and get the voltage back to normal. Burning ATP provides energy to the brain. This will then induce hyperglycolosis and metabolic uncoupling which contributes to behavior issues one might experience during a concussion.

Following, the burning of ATP forms lactate. Since the brain is burning a lot of ATP, there is lactate accumulation and calcium storing in the mitochondria. The mitochondria normally makes ATP. Calcium blocks the mitochondria from making ATP levels from returning to normal. Further, all this stress happening in the brain causes hypometabolism. Hypometabolism happens because the brain is using all this energy to balance ions, it isn’t able to use the energy to transport other things correctly. Calcium that is not stored in the mitochondria activates protease which is a protein that starts destroying other proteins, which then leads to apoptosis, AKA cell death. This whole process and the ions can get restored and fixed within roughly 10 days with proper treatment, but it is very easy to obtain other concussions during the healing process. If one gets a second concussion, the healing process takes much longer and there might be further long-term damage to the brain.

CBD Vs. THC?

Before explaining CBD as a treatment for concussions, it is important to note where it comes from and clear up any misconceptions that there might be about it. Cannabidiol (CBD) is a chemical found in the plant commonly known as marijuana or hemp. There are over 80 chemicals identified in this plant. One of which is the psychoactive chemical known as delta-9-tetrahydrocannabinol (THC). Like other chemicals in hemp, CBD can be extracted from hemp with little to no trace amounts of THC. Therefore, CBD does not get you high.

CBD as a Treatment?

In one study, researchers induced a concussion in male mice. After the concussion, the mice were placed in a comfortable environment during the experiment. Meanwhile, the mice were given oral CBD treatment. After 14 and 60 days there were 7 tests performed. Some of the tests showed CBD significantly improved symptoms in mice. The 7 tests included: Allodynia Test, Rotarod Test, Open Field Test, Resident-Intruder Test, Three Chambers Sociability Test, Tail Suspension Test and Microdialysis Test.

These were the results:

Allodynia Test-
- CBD treatment showed signs of reduced pain in mice.
Open Field Test-
- CBD treatment showed little significant changes in mice, but CBD did decrease “reckless behavior” shown by less rearing.
Resident-intruder test-
- CBD treatment significantly decreased aggressive behavior in mice.
Tail suspension Test-
- CBD treatment decreased depression like behavior, shown by decreased immobility in mice.
Microdialysis Test-
- CBD treatment administered prior to 60 days after trauma, normalized glutamate and D-Aspartate levels in the brain of mice.
Rotarod Test-
- CBD treatment showed no significant difference in motor coordination impairment in mice.
Three Chambers Sociability Test-
- CBD treatment showed no significant changes in social interaction in mice.

The data from this study shows promising results for CBD as a treatment for concussions. This being said, further research must be done to understand the full effects CBD has in concussions and on the body. For information about CBD as a treatment for other illnesses and side effects CBD might cause go to: https://www.medicalnewstoday.com/articles/cbd-oil-effects#side-effects

References

https://www.webmd.com/vitamins/ai/ingredientmono-1439/cannabidiol-cbd

https://www.frontiersin.org/articles/10.3389/fphar.2019.00352/full

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Concussion – Just an annoyance?

Posted on October 26, 2020 by / 0 Comment

Concussion is typically thought of as simply a hindrance to doing “normal” stuff, whether that be schoolwork, or getting back out onto the field, as most concussions happen through athletic means. But are the ramifications of a concussion just to feel a little dizzy and disoriented for a bit? Research into postcussed individuals suggests otherwise, as post concussion depression has been found to be a prevalent after-effect.

When people generally think of concussion, their first thought is typically not in relation to other mental disorders such as depression, but it should be. One study found that at least 35% of individuals that experience a traumatic brain injury (TBI) develop depression. This means that at least a third of people who get a concussion develop depressive symptoms afterward, which is quite a dramatic number. Another fact that was found is equally concerning: one study found that after only a mild traumatic brain injury, there was a 15% chance that the person developed major depression. This is the lightest and least serious type of brain injury (which you can get simply by hitting your head slightly too hard) and the worst, most serious type of depression, occurring in more than 1 in 7 people who experience a concussion. This is significant not only because of the depression part, but because this points to concussion as being more than purely “an annoyance”. In fact, the total prevalence across all severities of TBIs for major depression is 14-29%. In other words, up to a third of people who experience a concussion develop the clinically-worst type of depression.

This prevalence for depression isn’t universal however, there are certain people who develop more depressive symptoms than others post-concussion. Some risk factors are: being an older age when starting your first sport, having a history of substance abuse, and lower levels of education. Something that was found is that the severity of the TBI didn’t consistently lead to higher rates of depression, but losing consciousness was related to risk for developing major depression among mTBI patients. Some more demographic information reveals that ethnicities other than white experience greater post-concussion symptoms, and IQ has a negative correlation with such symptoms as well. These results are more speculative as to why they would be the case, but this highlights the need for greater concussion protocol and faculty in lower-socioeconomic areas, which unfortunately, by definition, have less access to such resources.

Figuring out why these results are the case has the ability to help numerous concussion victims recover with more vigor and not have to deal with bouts of depression while trying to recover. Neurologically speaking, one culprit could be the “differential patterns of calcium flux” that can occur postconcussion, which could be leading to less brain-derived neurotrophic factor (BDNF), leading to depression. BDNF is essential for cell proliferation and so without adequate amounts of it, cell levels and signalling may be messed up enough to contribute to startling equilibrium and causing depressive symptoms. The article also states that BDNF is directly associated with NMDA receptor alteration, which concussion causes as well. Another factor that would seemingly lead to higher depressive symptoms post-concussion would be increased GABA levels and signalling, as that has been found to increase related to depression. This however, is not the case with concussion, as GABA levels have been observed to fall in post-concussed individuals.

With the rates of depressive symptoms among concussed individuals being more than 1 in 3 people, more research should be done to figure out some of the mechanisms for bringing this number down. Preventing concussions in the first place would be the best option, but preventing post-concussion depression is also an important step in making things better for everyone who experiences this sort of thing, especially athletes. To loop back to my normal point, concussion is more than just an annoyance to be blown off as a headache, and more guidance should be brought into schools of all levels and education on the subject should continue so that everybody involved understands how to respond and properly help the individual heal.

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Ring Ring, Concussion Calling

Posted on October 25, 2020 by / 0 Comment

Your phone starts to ring, and you wonder who could be calling at this odd time of day. You pick up your phone, only to see that your concussion is calling. Debating whether to just send it to voicemail (it’s a pesky caller!), you ultimately decide you will hear out what it has to say. So, what does your concussion have to say to you?!

I’m hurting!

Your concussion begins the conversation by telling you that your brain is struggling, in more ways than one. It’s pretty common knowledge that concussions need a good amount of time to fully heal, but you might not know what exactly is going wrong.

When that blow to your head first strikes, the membranes within the brain’s axons get leaky, letting substances in and out that would normally be more tightly regulated. Because of this, sodium and calcium ions rush into the cell, leading to depolarization of the membrane. When the cell depolarizes, it is much more likely to fire an action potential. When the ion movement is going awry, the sodium-potassium ATPase works in overdrive to try to restore the normal concentrations. Here’s the kicker, though: the ATPase requires an immense amount of energy, so kicking it into overdrive means that we have an energy crisis—too much ADP and too little ATP.

The leaky membrane also means that the cell will face altered neurotransmission, specifically releasing WAY too much glutamate as a result of depolarization and wanting to fire. Another important issue is that the axons are suffering from injury as well, meaning that they are not functioning properly. While they may not die altogether, the injury can be so severe that the damage is beyond repair and the axon may never function properly again. The last point your concussion tells you is that the cells may start to die off. These aforementioned problems may lead to activation of proteases, which are enzymes that will destroy other proteins and ultimately lead to apoptosis: cell death.

After hearing all of that, you start to feel bad for your concussion! You thought it was just a nuisance, but you’re now realizing that it’s no wonder it is taking a long time to recover, there’s so many issues happening!

Take care of me!

After your concussion has told you some of the scary things happening at the molecular level in your brain, it moves on to tell you how to best recover, saying don’t spend time on your phone!

It may be common knowledge, but phone use is heavily discouraged when recovering from a concussion, as it can significantly prolong recovery time. In a study of 335 concussion patients, it was concluded that those with higher mental stimulation (from electronics, for example) needed on average double the time required to make a full recovery. Not something to mess around with! Think about it: with all of the issues mentioned previously, you do not want to be overstimulating your brain! The main takeaway here is that recovery time is largely dependent on a patient’s ability to avoid excessive mental stimulation.

But… do you need to halt phone use altogether?!

Use your phone wisely!

While it is known that phone use can prolong recovery times, there may be constructive ways to incorporate phone use into recovery. A mobile phone app called SuperBetter, used in conjunction with standard medical care, was demonstrated to improve outcomes and optimism for concussed teenagers. The app essentially functions as a gamified symptoms journal, where concussed individual reports symptoms and feelings, then the app turns those inputs into a game-like version of their feelings. This can help avoid social isolation associated with concussion recovery, especially since concussion patients are urged not to do anything that may be detrimental to their recovery. Within the app, users could form a network around their symptom log and comment and interact with other users’ posts, generating a cohesiveness between patients that may be looking for some more interaction when able. The main takeaway here is that, while you shouldn’t be overstimulating your brain and harming recovery, you can use what little screen time you have in a positive manner, leading to a more efficient recovery.

With that, your concussion decides it has said enough. You hang up the phone, in awe at how much you didn’t know about what’s going on in your brain, and how you can best help it recover. Maybe now you’ll give your concussion more credit.

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Got Myelin?

Posted on October 25, 2020 by / 0 Comment

Does your head hurt? Do you have a headache or sore neck? Are you sensitive to light and/or sound? These are just a few of the basic questions one gets asked while trying to make a diagnosis that lacks a more accurate way of assessment: a concussion. Otherwise known as a TBI (traumatic brain injury), it is something that most probably worry about getting after suffering a blow to the head or may be the reason altogether as to why parents steer their children towards a sport/activity with minimal contact. What exactly happens inside of the brain when it is suddenly thrown around, concussion or not? This will be explored below, as well as a term that may not regularly be incorporated with TBIs: myelin. Let’s keep reading!

A Journey Inside the Brain

Oh no! Your high school quarterback has just been diagnosed with a concussion from the football game last night. Thinking back to just seconds after he was hit from behind, let’s examine what occurred microscopically inside of his brain as a result. The sudden movement inside his skull most likely started out with neurons becoming “leaky”, or more permeable for ions to flow in/out of the cell. For TBIs, there is an extreme influx of calcium and sodium ions with an efflux of potassium ions.

This sets off a series of reactions, starting with glutamate being released from these neurons and the cell uses up much of the ATP it has stored inside. This shortage results in the cell needing to generate more ATP to maintain other crucial reactions within the cell which creates a state known as hyperglycolysis. The lack of oxygen entering the body compared to the amounts being consumed intracellularly results in an unfavorable side product being formed with ATP (lactate) and extra calcium getting stored in the mitochondria. Shrinking and running out of options, these cells quickly realize that they are now only doing more harm than benefit and decide to turn to apoptosis: programmed cell death.

And to think- all of this is happening before he even stands back up from getting tackled.

Good Old Myelin

So now you probably are still curious about the cliffhanger I left you with from the beginning about this “myelin” stuff and how that plays a role in the brain and TBIs. Myelin is what wraps around the axons of neurons not only to help propagate action potentials, but also towards generating plasticity and cognitive abilities in the brain. Damage to these areas can result in a slower processing speed due to signal disruptions. Interestingly, humans are born with a pretty unmyelinated central nervous system, and so myelination is not something that is present until after our first couple years, which after still continues to contribute towards thickening the protective layers around individual axons in the ever-maturing brain. Different areas of the brain develop myelinated axons at different speeds, making it a very unfortunate scenario when an individual may develop a TBI in a place that is just underdeveloped compared to the rest.

Takeaway message: Younger individuals have less myelination in their brain and a more flexible set of axons, but this results in a higher vulnerability for damage to occur, therefore this ultimately leads to cellular dysfunction and/or apoptosis.

Looking Ahead

Sadly, rest is the current go-to “antidote”, as there remains no over-the-counter medication that can be prescribed for individuals suffering from TBIs. Future advancements that are being developed with the growth of technology and science give optimism for things such as biomarkers to be not-so-much of a distant thought or conversation to be had.

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

Community/Health/Hot topics

Concussion and Aggression: “Infuriating” Side Effects

Posted on October 24, 2020 by / 0 Comment

Concussions, also known as mild traumatic brain injuries (mTBIs), often have unpleasant side effects: headaches, nausea, confusion, amnesia, trouble sleeping, and difficulty with concentration and learning. Most of the items on that formidable list tend to dissipate in a matter of weeks as the brain heals and starts to go back to normal. However, months or even years following the mTBI, a significant proportion of people begin to show other symptoms: permanent emotional symptoms ranging from increased levels of anger and aggression to complete personality changes. How can a concussion change your personality—and what does it even do to your brain in the first place? To answer those questions, let’s take a closer look at the neurochemistry.

What happens to the brain after mTBI?

The changes described in the following list take place in neurons, which are brain cells that send signals to one another to let us think. Neurons are shaped a bit like an oak tree. Signals come into branches at the ‘top’ of the tree, travel down the neuron’s axon, which would be the tree’s trunk, and go out through the roots to the next neuron. The signal that comes into the branches is a neurotransmitter chemical. The neurotransmitter either tells a neuron to fire (which means to be activated and pass the signal on to the next neuron, which passes it to the next, and so on), or not to fire. If a neurotransmitter tells a neuron to fire, molecules that have positive or negative electric charges cross the cell membrane (a thin membrane like a water balloon that lets molecules go in and out) and change the voltage of the entire neuron. Becoming more and more positively charged makes a neuron want to fire and keeps a signal going.

Phew, lots of neuroscience there—but it’s important background information to understand concussions! Keep that treelike structure and the way neurons fire based on voltage in mind while we look at a basic version of the cascade of molecular effects following a blow to the head.

Neurons are physically damaged from the impact. The damaged axon (remember the tree trunk from earlier?) has a harder time carrying signals and might even stop working entirely.
The cell membrane, also damaged from the impact, becomes leaky to ions (molecules that have an electric charge). Lots of positively charged ions like calcium and sodium leak into the neuron.
With this positive charge, the neuron is activated and wants to fire. To fire, the neuron releases a neurotransmitter called glutamate which travels to more neurons and makes them fire, causing a lot of activity in the brain.
The neuron knows that it has too much positive charge, so it spends lots of energy (in the form of ATP molecules) pumping those positive ions back out of the cell trying to get back to its normal voltage.
The byproduct of burning ATP at such a high level is lactate, which starts to build up in the brain.
All of the extra calcium (which is still leaking into the cell) is stored in a part of the cell called the mitochondria that normally makes ATP. This blocks the mitochondria’s function and prevents ATP levels from returning to normal.
The calcium that isn’t stored in the mitochondria can activate a protein called protease that starts destroying other proteins and leads to apoptosis—cell death.

This altered function lasts roughly ten days following mTBI, directly causing the harmful symptoms of concussions. The ions flowing into neurons cause headaches. The damaged axons cause cognitive difficulty, making it harder to think, remember things, or react quickly. Steps 1-6 above slowly go back to normal as the brain heals, cell membranes are repaired, and neurotransmitter levels begin to return to normal. The headaches, ‘foggy brain’, and other symptoms mentioned above go away in most mTBI patients as days or weeks pass.

However, step 7, cell death, is irreversible. This protease-caused cell death leads to the permanent emotional symptoms that we see in some mTBI patients: anger, aggression, and personality change.

How often do emotional side effects occur, and what do they mean?

28.4% of people who suffer mTBI report an increase in aggression, whether physical or verbal. However, unlike cognitive changes discussed above, these side effects don’t tend to get better on their own, and the emotional changes show up after months or even years have passed since the mTBI. Late onset and irreversibility are signs that emotional side effects are caused by the final ‘cell death’ step of the cascade we looked at earlier.

Some have theorized that since mTBI can cause increased aggression, people who sustain repeated head injuries (like professional athletes) are at a high risk of developing violent behavior. People frequently cite statistics like highly publicized levels of domestic violence among professional football players. However, this correlation has not been sufficiently studied to implicate mTBI as the cause; it is likely that people who are successful at professional sports may have higher baseline levels of psychological factors like aggression and risk-taking, or that an unknown third variable exists. It’s also difficult to pinpoint causation on mTBI when these symptoms develop unpredictably months or years after the injury.

Beyond increases in aggression, some report in themselves or loved ones who have experienced mTBI a complete personality change. Janet Cromer, a college professor, writes about having to completely re-form her relationship with her husband after he sustained an mTBI and began to experience angry outbursts that he had never displayed previously.

Is there any way to avoid permanent emotional side effects from mTBI?

Since mTBI symptoms vary case-by-case, it is difficult to predict if emotional side effects will arise. One extremely important preventative measure is avoiding a second head injury while still in the vulnerable ten-day period after the mTBI. Sustaining a second injury while still recovering from the first has been shown to put much more strain on the healing brain and increase unpleasant symptoms. Resting both physically and mentally during the vulnerable period can also reduce the strain on your brain and give a chance to return the molecular cascade we looked at back to normal.