TBI and Inflammation

by Dr. Perry Maynard

According to The Centers for Disease Control (CDC), it is estimated that 1.7 million people suffer a traumatic brain injury (TBI) in the United States each year and 5.3 million are living with TBI-related disability. Traumatic brain injuries are complex injuries that we are just beginning to understand and are now realizing that the immune system plays a large role in brain inflammation after the initial injury, but also in our ability to heal and recover from the injury. When an individual suffers a head injury there is development of damaged tissue. The severity of the injury will usually determine how much tissue is damaged from the initial injury. 

The damaged tissue needs to be presented to the immune system so that the “cleanup crew” can come and clear the damaged neurons. Although this is an important initial step, it also can create excessive amounts of inflammation, which is why the more damaged tissue there is, the more risk there is of over-activation of inflammation. Later, we will discuss the important brain cells that help this process go smoothly. 

Another process that occurs early on is changes in electrical charge within the cell. Our brains have certain types of natural neurochemicals that calm down the brain, and other neurochemicals that excite and rev up the brain. One of the chemicals that revs up the brain is glutamate. Early on after a head injury, you get a large increase in glutamate outside the cell. The excess glutamate can bind to certain receptors on neurons and create what is called excitotoxicity. This over-stimulation of neurons can create even more damage and more death of neurons in the early stages of a head injury. The critical key is the dance between pro-inflammation and anti-inflammation signaling. Mice studies have shown that too little inflammation can hinder recovery and  create greater motor impairment and larger lesions, while too much inflammation can also cause further swelling and blood-brain barrier disruption. This is also most likely why certain people with pre-existing conditions that prime the immune system and create excessive inflammation may have worse outcomes than individuals who are healthy. This is something I see in patients all the time.

Earlier, we talked about how damaged tissue in the brain can create inflammation and that the immune system must attempt to clear that debris and rebuild the damaged circuits. This is where we will discuss the cells that aid in this process, the microglia. I want you to think of microglia cells as the “cleanup crew,” the remodeling team in a home renovation. When buying a house to remodel, most likely there will be some damaged parts. Maybe the floor is warped or the wood in the foundation is rotted and you need to make updates so that the house is safer and functions better. Let’s say the house experienced a flood from a storm and it ruined some of the infrastructure of the house. It doesn’t make sense to remodel the house until you have cleared out the damaged floor and drywall. Once that is done you can begin to rebuild.

This crew in your brain, the microglial cells, have three different modes. In a healthy state, the microglial cells are non-reactive, in a resting state, because the home has no damage. But they are always sensing the environment within the brain to see if their help is needed. When they sense inflammation and damaged tissue, they morph into what are called M1 microglia, the crew that rips apart and helps clear the damaged aspects of the house (brain). This mode of microglia is considered the more inflammatory form, but when well-regulated, it is thought to possibly be neuroprotective. However, when it is prolonged or exaggerated, it can lead to things like second-impact syndrome. The M2 form of microglia is thought of as more anti-inflammatory and plays a role in healing and tissue remodeling. This is the part of the home crew that builds new floors and walls once the damaged ones have been ripped out. 

Research has demonstrated that the severity of the head injury can alter the ratios between M1 and M2 cells and the balance between the two. Just like with most things, it is most likely a fragile balance between the two that allows the ability to work together to resolve inflammation and repair the damaged areas within the brain. Too much of one is most likely not a good thing, it is about balance.

So, as you can see, the immune system plays a large role in recovery from a brain injury within the first few days, but also the first few months. Research has suggested that we should be focusing on four major things after a head injury

1. Limit the acute pro-inflammatory response to the level needed for clearance of debris and danger signals.
2. Reduce glutamate excitotoxicity
3. Balance microglial cells to promote an anti-inflammatory and pro-regenerative immune system.
4. Prevent the development of chronic neuroinflammation and risk for brain autoimmunity 

You may be starting to see how the things in everyday life that drive inflammation may affect one’s recovery. While the list below may not seem logical in their connections to your brain, they can alter the way the immune system works and create excessive amounts of inflammation. The following can hinder and prolong one’s recovery from a traumatic brain injury

1. Blood sugar dysregulation
2. Food reactions
3. Hormone imbalances
4. Poor sleep hygiene
5. Excessive stress/Overtraining
6. Chronic infections
7. Environmental toxin exposure
8. Anemias and things that affect circulation
9. Autoimmune disorders
10. Gut Dysbiosis

All of these, along with a majority of health conditions, have some aspect of chronic inflammation and alterations in the immune system. This is why it is so important that a doctor treating head injuries take these things into consideration. If you are a patient suffering from persistent concussion symptoms it is critical that you are working with a practitioner who understands the interplay between your immune system/inflammation and things like post-concussive syndrome. This is also where the implementation of certain types of diets, specific supplements, hyperbaric oxygen therapy, stem cells, and immune-modulating peptides may have beneficial roles in improving outcomes from traumatic brain injuries.

Dr. Perry Maynard specializes in the management of complex neurological cases. He enjoys taking principles from cutting-edge neuroscience and applying them to sports rehabilitation and overall human performance. www.integratedbraincenters.com