Concussions: otherwise known as TBI or traumatic brain injury
June 27th, 2022
Concussion is an injury that is a trauma to the head where the skull stops rapidly and the inner brain gets rotationally or linearly moved beyond its normal confines leading to microscopic nerve injury and subsequent inflammation. The traumatic process occurs suddenly and can have unconsciousness as a consequence. Whether the patient is unconscious or not for a period of time, a full work up is necessary to understand the gravity of the injury and the subsequent therapy.
If your child suffers a head injury during a sporting event, have her or him assessed for cognitive delay and neurological symptoms before returning to play. If your child is determined to have suffered a concussion, expect to have a delayed return to play and school work based on symptom resolution.
In our clinic, most concussions last 1-3 weeks before all symptoms are resolved. It is imperative to let the brain rest as needed during the recovery phase. We recommend brain rest to symptom comfort. Old data promoted complete rest and that did not turn out to be useful in controlled study. One should stop serious exercise, vigorous physical activity, difficult school work, excess TV, all videogaming, and other brain over-stimulating activities until they are symptom free. Strict adherence to the plan is critical. Far too many teenagers and coaches do not follow the prescribed course and have protracted healing issues. The NFL, historically, had been the poster group for what not to do in brain health.
Repeated TBI's are associated with increased risks for depression, neurodegenerative disease and decreased overall health over time.
Concussions can alter a child's personality temporarily. Be aware and patient with them while they heal.
As with most disease that we discuss, the antecedent condition of the individual prior to injury has a major influence on outcome and length of time to recovery. Being systemically inflamed for any reason, increases length of recovery time.
During an acute injury the brain goes into a hyper metabolic state burning a lot of glucose for energy to handle the need of the overactive neurotransmitter pumps. This causes the brain cells to increase glucose utilization leading to increased mitochondrial burning byproducts called reactive oxygen species which damage local nerve cells triggering local inflammation. Then the glucose stores become depleted leading to a hypo metabolic state with low glucose use. This is the critical time where another head trauma would be catastrophic. The global inflammation leads to macrophage activation, cellular destruction and potentially self antigen tissue presentation. For a detailed look read the science next or skip it.
Science Heavy: Molecular cascade of events after a mild traumatic brain injury. The initial mechanical injury causes mild membrane disruption in the nerve, axonal damage, and indiscriminate neurotransmitter (glutamate) release and activation of ion channels, such as the NMDA receptor. Deregulation of Na+/K+/Ca2+ flux leads to excitotoxicity—a massive influx of calcium and an efflux of potassium and the release of the neurotransmitter glutamate. Ca2+ influx also exacerbates damage to the axonal structure and causes mitochondrial dysfunction. ATP-dependent Na/K pumps function at an elevated capacity, creating a hypermetabolic state generating oxidative stress that can result in cellular damage. Glucose stores become depleted due to the hypermetabolic state, resulting in a hypometabolic state, with low glucose utilization. This hypometabolic state may last for months in severe cases, and, during this time, the brain may be particularly vulnerable to repeated injury (dashed arrow). Concurrently, inflammation due to microglial activation occurs soon after the concussive injury, causing damage to cellular structures. Ultimately, the combination of oxidative stress, inflammation, excitotoxicity, mitochondrial dysfunction, and axonal damage results in neuronal apoptosis. The ω-3 FA DHA has been shown to address several of the hallmark pathologic features of this injury, such as excitotoxicity, oxidative stress, and inflammation. NMDA, N-methyl-D-aspartate; ROS, reactive oxygen species. (Barrett et. al. 2014)
The immune system is activated and begins a process of cleaning and repairing the damage. For this part, let us focus on the microglial cells, a type of resident macrophage (large thing that devours) that covers every square millimeter of the brain. They are poised to eat anything that is foreign or dangerous to protect local brain tissue. These cells make up 80+% of the immune cells in the brain telling us of their massive importance. They come in two flavors, M1 which is inflammatory and M2 which is the opposite. To really understand what is happening during a TBI at the immune level we have to first understand that the brain is going to protect itself at all costs. The cells in the brain have specialized pattern recognition receptors, called PAMPs and DAMPs, to find pathogens and our own cellular debris in local tissue spaces. These receptors are cranked up and peak 7 days after the TBI to recognize the damaged cells and trigger local microglial cells to act. There is also a concomitant increase in NFkB which promotes inflammation and again peaking at 7 days. These actions are also affected by the permeability of the blood brain barrier and the infiltrating circulating immune cells making this process exceedingly complicated. But, this is a critical process for species survival as the removal of pathogens and damaged cells reduces further damage leading to dysfunction globally.
Let's take an example, a teenager's head is hit by a baseball causing a brief loss of consciousness. The microscopic cell based response is that neuronal cell membranes and the axons get stretched and disrupted by the TBI leading to local neurotransmitter excesses and cell debris release triggering DAMPs to be recognized by the pattern recognition receptors. The end result is a triggering response that recruits local microglial cells to clean up the damaged cells. These microglial cells will then recruit inflammasomes to form and fire up burning the damaged tissue for clearance. There is also the release of cell signaling inflammatory cytokines to recruit other immune cells to the area. These cells are acting in an inflammatory way on purpose for damage resolution and are more aggressive when recruited from outside the brain. Thus, the more neutrophils and macrophages that show up, the more inflammation there will be. Then the microglial cells should shift from an M1 type to a resolution based M2 type. Then if all goes according to plan, the cells are repaired and normalcy is restored.
However, in some individuals this process is broken and microglial cells stay pro inflammatory recruiting further volumes of immune cells that cause more damage and the cycle persists to the detriment of the person. The cause of the why remains the object of much research. If enough tissue is damaged, the debris can be presented to the immune system leading to autoimmune issues over time. Suffice it to say that our lifestyle choices that are often discussed here appear to be driving these issues. See the picture above for details. Sleep, diet, stress and sedentary behavior are the main drivers of immune dysfunction. Obesity and metabolic syndrome are highly associated with poor outcomes. These lifestyle choices drive changes in metabolic, hormonal and systemic inflammatory pathways that leave us polarized toward excessive immune based inflammation.
Another large area of research which is covered in this weeks Journal Club Podcast is the Omega 3 Fatty acid space. These fats enter our bodies from cold water fish, grass fed animal meats and to a lesser extent in some seeds and nuts. It turns out that based primarily on animal model studies and some human trials, these fats are heavily involved in the production of specialized pro resolving lipid mediators: resolvins, protections and maresins. These SPM's drive the resolution of neuro-immune inflammation leading to more rapid recovery.
Let's look at the microbiome: What we know about TBI is evolving rapidly. There is a cross talk between the brain and the gut post injury. There was a research paper published in the November 2017 edition of the Journal Brain, Behavior and Immunity. The findings were staggering for the future of health post head injury. The results show that post injury, people develop a classic leaky gut allowing intestinal bacterial pathogens to travel out of the gut to other sites in the body. Subsequently, they develop significant systemic bacterial infections which can kill or at least hurt the injured person.
Statistically, post TBI human individuals are much more more likely to die from bacterial infections than non TBI patients in the hospital.
In the animal model, the mice underwent a traumatic brain injury which caused a period of intestinal leakage that lasted for greater than 30 days.
The second part of the study proved the cross bidirectional talk of the brain and the gut bacteria. They infected the mice with a pathogen, Citrobacter rodentium, known to cause infection in the gut. The animals that had TBI had significantly greater brain inflammation if they were co-infected with this pathogen. The infected animals lost more memory cells and suffered significantly more.
Why is this significant?
If you have a dysfunctional gut microbiome prior to suffering a TBI, you a likely to have a significantly worse outcome. We know by testing that we are doing in clinic that most of our children are on the dysfunctional side of the balance point. This is yet another piece of evidence in a long line data teaching us that we are tremendously negatively affected by our diets and microbiome if it is dysfunctional.
As with all things in nature, prevention of these events would be ideal. One is easier to protect against than the other. The "easy" one is to have a robust and healthy fiber based diet for years prior to the event to prevent this inflammatory worsening. The hard part is to choose it. Preventing TBI itself is also important, but harder to do if you are an athlete.
What to do based on what we know today -
Image from Marques Frontiers in Nutrition - check out this link for a nice graphic that delineates the lifestyle risk paradigm.
1) Fiber will protect you by providing the food for the good microbes to consume and proliferate. Eats lots of vegetables, nuts, seeds and fruits for the rest of you life!
2) Gluten is known to worsen intestinal permeability and blood brain permeability in certain individuals. See the research of Alessio Fasano. Avoid gluten post injury for a month. If you have any symptoms of celiac disease or non celiac gluten sensitivity, avoid gluten in general.
3) Avoid all pro inflammatory foods including vegetable oils, fried food, processed white foods (bread,pasta,crackers, chips, cookies,etc..), corn fed meats, farmed fish, diet and sugar based beverages.
4) Omega 3 fatty acids in fish oil can protect against some of the inflammatory damage by balancing the inflammatory fatty acid system. Take provider recommended fish oil or eat small oily fish every week.
5) Control the variables that are controllable. Wear a helmet or specialized protective gear to lessen the impact in sports. Wear seat belts and use car seats appropriately to prevent car wreck induced head injuries. Offensive and defensive linemen in football and rugby are at particular risk based on the repetitive ram like hits. I am in favor of contact minimized practice especially for these linemen. Check out the Virginia Tech Helmet information quality link.
6) Take high quality refrigerated multi species probiotics.
7) Get 7 to 9 hours of sleep highly based on your chronotype.
8) Minimize mental stress by prayer, meditation and rest.
9) Exercise 30 minutes every day.
10) Consider anti-inflammatory herbs like curcumin and ginger as an adjunctive therapy via supplement or in consumed foods.
Honestly, the same things that help protect against a negative Covid outcome are mostly at play here. See the Covid newsletter for the thoughts and plans here.
Lifestyle choice is key,
Neuroscience News Article
Original Article Citation
Alessio Fasano Video
Alessio Fasano Article
Barrett Advances in Nutrition
Zheng Frontiers Immun
Verboon Frontiers Immun
Marques Frontiers Nutrition