- Types of Damage
- Microglia: Cells That Support And Nourish
- Neuroinflammation: What It Is
- Microglia and Fever
- Thalamic Inflammation
- Injury Unleashes Cortisol
- Energy Consumed
- The Wandering Nerve: The Vagus Nerve
- Why Emotional Trauma Is Hard To Treat
Brain injury is not a single event, but a process over time initiated by an event. The injury becomes the sum of the cause plus the hidden cascading damage after. I call this site Concussion Is Brain Injury because concussion is least considered a brain injury, but this site is for all types.
Every brain injury is unique. Every cause results in a different looking brain injury. But fundamentally, they all result in a malfunctioning brain that requires rebooting, repairing, and rewiring. They require specialists and lay people alike to understand that whatever the outward cause, inward processes add to the symptoms and increase the risk of later-in-life dementia even in the face of spontaneous “recovery.” Science is more and more starting to understand that and how to heal it.
Whatever the cause, brain injury is a change in the way the brain works.
- Biochemical changes start immediately. (I don’t go into this as it’s very technical, but scientists and specialists can look this up.)
- Cells called “microglia” that normally support and nourish neurons start attacking neurons and eating their synapses.
- Neurotransmitters go out of balance as a result while the attacking cells send messages through the brain and into the immune system to proliferate the attack.
- The autonomic nervous system goes into permanent fight, flight, or freeze mode.
- Organs that produce cortisol go into overdrive and flood the brain with it.
- Energy drops.
- The damage cascades as processes meant to fight infection or injury aren’t shut off.
- Blood flow shuts down.
- The nerve that wanders from the brain to the heart, lungs, digestive system, and external ear shrivels up.
- Brainwaves change.
- Outward symptoms appear in cases where the initial injury seemed mild or symptom-less, and they may worsen as the injury cascades unseen.
The brain is normally a happy little place of neurons that send messages that give us our emotions, thoughts, senses, movements, heartbeat, etc. and their supporting glia cells along with tiny but mighty defenders. These messages show up in brainwaves — squiggly lines of electricity on a graph.
The cause of the injury may end in seconds; but the downward cascade is only just beginning.
The defenders go on high alert. They transform into tarantula-like creatures machine-gunning chemicals at the neurons. They forget to take out the garbage. Then they gobble up neurons’ connections with other neurons while sending out microparticles to alert defenders in still healthy parts of the brain and body to do the same. Messages go haywire. And defenders in the body start attacking healthy tissue there, too. Meanwhile, the brain launches into fight, flight, or freeze mode. Chemical messengers get released; these neurotransmitters scream, “Danger! Danger! Danger!” and tiny little organs deep in the body stream out cortisol in response. Neurons don’t get fed anymore. The brain gets rather tired with all this screaming mimi stuff. It demands naps after the littlest activity but can’t sleep. Blood flow slows. And the big nerve that wanders from the brain to our heart, lungs, guts, and external ear shrivels.
The messages that give us our emotions, thoughts, senses, movements, heartbeat, etc. become muddled, dead ended, and chaotic. So our thoughts, emotions, movements, etc. may, too. But even if we look normal, our brainwaves look dead or frenzied or both. The garbage builds up, setting the brain up for dementia years later. And the chemical that can stop this cascading reaction and start the glia and defenders repairing the neurons and taking out the garbage again decides to stay home. So we have to do its work for it through neurostimulation therapies.
Key Aspects of the Physical Processes Underlying Brain Injury
There may be one event, but it’s a time-delayed cascading injury involving the immune system. Keep this in mind as you read below what brain injury actually is. Different causes will add their own unique factors to this, for example, stroke would add bleeding into the brain.
Microglia: Cells That Support And Nourish
Microglia are tiny immune cells in the brain and body that make up one-tenth of all brain cells. They maintain the brain, repair neurons, defend the brain, but can also cause great havoc. These cells have arms that monitor neurons and the blood-brain barrier, and these arms can stretch and shrink, depending on what they sense and what they decide to do. Microglial bodies can also change shape from small to elongated or to round, big, and fat or to other shapes.
Microglia grow new neuron appendages; they provide nourishment for neurons; they eat proteins that if left to accumulate would lead to the plaques of Alzheimers.
Microglia also eat synapses they “see” as inactive or lazy in a process called “phagocytosis.” This process enhances the brain’s efficiency and energy use.
In the video below, microglia in green eats a neuron in red as seen in the far-right merge movie:
Synapses are the spaces between neurons through which neurochemicals flow to transmit messages from one neuron to its neighbour(s).
By eating synapses, the microglia are essentially eating neurons. In this way, they prune the brain — a good thing during early childhood development, for pruning enables good brain growth. Think of it like pruning a rose bush to produce more and bigger roses and architect a bush structure into one that’s tidy, healthy, and disease resistant.
Microglia promote repair, but they also cause inflammation.
Microglia are ramified cells. They have a central body or soma with complicated arms or processes coming out of them. De-ramification would mean that they lose that complex network of arms. Essentially, they go from small body with lots of arms to fat or elongated bodies with few arms (see image below).
“microglia are not actually resting but continuously scanning their environment (Nimmerjahn et al., 2005; Olah et al., 2011), pruning synapses and regulating neuronal activity, providing a “fine-tuning” of neural circuits (Paolicelli et al., 2011; Schafer et al., 2012; Miyamoto et al., 2013) and neurotransmitter signaling/synaptic transmission (Li et al., 2012; Béchade et al., 2013; Domercq et al., 2013).
In situations of neuroinflammation or after injury, a stepwise de-ramification of microglia has been repeatedly observed. Thus, ramified microglia can transform into an “activated state”, characterized by swollen ramified cells with a larger cell body and shorter, thick processes, or alternatively microglia can adopt a “reactive state”, typically small, spherical cells, but can also exhibit rod-shape or amoeboid-like morphologies (Davis et al., 1994).Maria del Mar Fernandez-Arjona, Jesus M. Grondona, Pablo Granados-Duran, Pedro Fernandez-Llebrez, and Maria D. Lopez-Avalos. Microglia Morphological Categorization in a Rat Model of Neuroinflammation by Hierarchical Cluster and Principal Components Analysis. Front. Cell. Neurosci., 08 August 2017. https://doi.org/10.3389/fncel.2017.00235
Neuroinflammation: What It Is
In the presence of infection or environmental toxins, chronic stress, childhood abuse, brain injury, and such like, microglia can get rabid and eat too many synapses, including healthy ones. They release the same inflammatory chemicals the immune system releases in response to infection and chronic stress. These cytokines, such as C-Reactive Protein, Interleukin-6, and tumour necrosis factor, attack neurons. This combination leads to neuronal loss — and probably damage to their corresponding neural networks — and is called “neuroinflammation.” This loss or neuroinflammation shows itself in symptoms corresponding to the areas of neuroinflammation, symptoms such as memory loss or depression or anxiety or schizophrenia. In addition, microglia will stop sweeping up beta-amyloid proteins and other waste, allowing toxic waste to accumulate and leading to Alzheimer’s disease.
Neuroinflammation and Brain Injury
Microglia, in the presence of traumatic injury, change shape to big and bulky, like fat spiders. These microglia jet out microparticles that swim to other brain regions to make other microglia like them. Those happy microglia turn into bulky attackers of neurons. And the microparticles, being in the cerebrospinal fluid, also enter the lymphatic system in the meningeal spaces between the brain and skull. The lymphatic system is our immune system’s highway. This highway allows these microparticles to zoom into the rest of our body. They activate the white blood cells to attack the body.
Although researchers see this change as bad, I wonder if it’s actually good. Dead neurons need to be eaten and digested in order to make room for new neuronal growth. Damaged neurons may be too far gone for microglia to repair, and so evolution has taught them to engulf them instead. Sending messages down the neural network to healthy microglia to change into tarantulas to chow down on healthy synapses may be evolution’s way to ensure energy isn’t being used to generate signals that end in dead tissue and go nowhere. The brain needs energy to regenerate and to create signals that are productive; it can’t waste it on dead-end signals.
As I note under Thalamic Inflammation below, isolated neurons creating dead-ended signals lead to chaotic neuronal firing, which creates anxiety. Anxiety may be to neuroinflammation what hot, red skin is to inflammation around a wound.
Why Does Neuroinflammation Not Stop?
The problem is that once the work is done to clean out the damage, the microglia don’t stop. Something has to trigger them to change to their form that stimulates neuronal growth and feeds them. What that something is, doesn’t happen in many people. Perhaps it does in those who look like they’ve recovered from concussion.
Interleukin-10 is a cytokine that stops the action of cytokines like C-Reactive Protein, Interleukin-6, and tumour necrosis factor.
“In concert, the available data indicate that glia can produce IL-10 [Interleukin-10] and the related cytokines IL-19 and IL-24 in a delayed manner, and these cytokines can limit glial inflammatory responses and/or provide protection against CNS insult.”Amanda R. Burmeister and Ian Marriott. The Interleukin-10 Family of Cytokines and Their Role in the CNS. Front. Cell. Neurosci., 27 November 2018. https://doi.org/10.3389/fncel.2018.00458
However, researchers don’t know why microglia do not switch to producing interleukin-10 once the injury event is over and the debris eaten up, or if other cells must start producing it in order to turn microglia back to their supportive nourishing role. That’s why medicine must provide treatments that reboot, repair, and rewire.
Neuroinflammation and Neurotransmitters
By damaging healthy neurons or further damaging injured neurons, microglia change their production and uptake of the neurotransmitters that neurons use to communicate with each other. Dopamine and serotonin drops. But the solution is not a medication to increase their levels, for their drop is a symptom not a cause of the brain malfunction. That’s why drugs used for various mental illnesses are not appropriate for brain injury. The cause is injury that changes microglia, which change neurons functioning, not neurotransmitters being out of whack.
Microglia and Fever
Another factor: Fever is one sign of inflammation, that is, an activated immune system. Temperatures higher than normal but below the fever threshold can happen from neurons regrowing after injury.
Fever or temperatures of 37.5-38°C from nervous tissue regrowing is nine times more likely to occur in those with DAI (diffuse axonal injury) after a trauma. Unfortunately, fever is associated with more severe symptoms. Perhaps because people with brain injury don’t sweat when they have fever.
This presents a conundrum. Somehow some microglia are regrowing neurons while others are busy still damaging them. Not surprising since researchers have already discovered different kinds in addition to how microglia will change shape and function.
Microglial activation in the thalamus leads to thalamic inflammation. That, in turn, leads to a damaged corticothalamic loop. This loop is instrumental in relaxed, focused attention.
The corticothalamic loop comprises neural pathways that connect the thalamus to the cerebral cortex. Imagine clothes rotating in a dryer. Like clothes rotating up and then back down, electricity loops up to the cortex and back down to the thalamus along neural pathways. This looping creates synchronized alpha brainwaves.
qEEG brain biofeedback takes advantage of this loop by training the cerebral cortex involved in the loop and thus (re)activating the pathways down to the thalamus.
Inflammation results in electrical blockages that interrupt the normal synchronization electrical pulse that creates alpha brainwaves. Dave Siever wrote in his paper Audio-Visual Entrainment and Diffuse Axonal Injuries/Interruptions, 11 June 2016: “Carla Shatz in 1992 said, “Neurons that fire together, wire together, and neurons that fire out of sync, lose their link.”
Without this synchronization pulse, instead of working together in the neural pathways, neurons become isolated. Imagine the dryer drum going haywire. Some clothes stick at the bottom, some may reach the top but then drop straight down instead of looping round. They don’t go round all together. Similarly, isolated neurons randomly fire at 1 to 2 Hz — the sub-delta brainwave frequency — and lose their link to each other. They also lose their link to other areas of the brain that would normally send or receive information from them. In addition, EEG shows choppy beta brainwaves. The result is that the traumatically injured brain with DAI no longer has a ratio of 3:1 alpha to beta, but 1:1. That’s too little alpha. Agitation and anxiety result.
Injury Unleashes Cortisol
With any brain injury cause, when the brain doesn’t function well, it goes into fight or flight. That’s the sympathetic or arousal arm of the autonomic nervous system kicking on. That releases cortisol, which floods the brain. Dopamine and serotonin production shut down; norepinephrine — the neurotransmitter of fight or flight — becomes depleted. Blood flow in the frontal lobes where attention and impulse control reside also shuts down.
Cortisol production doesn’t ease up. Instead, cortisol interferes with brain-derived neurotrophic factor (BDNF). Neurons become malnourished, and they literally wither away. Worse, hippocampal neurons that facilitate memory die. It takes energy to stop this cycle, but the brain becomes so tired that it cannot put on the brakes. Anxiety thus rises out of control, and cortisol continues to pump out. The sympathetic arm of the autonomic nervous system remains dominant (which happens in chronic stress as well). Perhaps this is why the vagus nerve atrophies. Being primarily parasympathetic, it isn’t being used much.
This sympathetic dominance combined with damaged areas not functioning, makes healing not possible without neurostimulation treatments.
Meanwhile, the brain consumes vastly more energy as it attempts to repair itself. And, worse, the mitochondria — neurons’ little engines — malfunction. They can’t produce energy to power their cells. That’s why we need to find a way to get glucose straight to the brain and bypass the body’s propensity to store it in fat cells in addition to stopping neuroinflammation once it’s done its work. Glucose is the brain’s fuel.
The Wandering Nerve: The Vagus Nerve
The tenth cranial nerve is called the “vagus nerve” because it wanders through the body. It runs from the brain, down your neck just behind where you can feel your pulse, and into your torso. It reaches into your larynx and pharynx, your lungs and heart, your bowels and external ear (this latter may account for why acupuncture in the earlobe works). And it’s part of the immune system.
When the body senses infection, injury, or inflammation, T-cells activate white blood cells to attack the source as well as travelling up the lymphatic highway into the brain to tell microglia to also start machine-gunning cytokines at neurons and eating synapses. This leads to fatigue, despair that nothing is good, and pushes a person into bed so that the immune system can use all the body’s resources to fight back the infection. This “sickness behaviour” of malaise also prevents a person from wandering around spreading viruses and bacteria to everyone they meet. It protects the population from the sick person. Unfortunately, chronic stress and brain injury create the same kind of response.
The brain sends signals down the vagus nerve to activate the immune system along its branches. Some researchers theorize that the vagus nerve can also signal microglia to start sickness behaviour when, for example, it detects bad bacteria in the gut or that the gut’s microbial population is out of whack. Hence, the rise in probiotics to restore a healthy balance. (Note: not all probiotics are the same.)
This connection of brain, vagus, and immune system is called the “inflammatory reflex.”
Heart Rate Variability
The vagus nerve is primarily paraympathetic. The autonomic nervous system comprises the sympathetic and parasympathetic arms. The sympathetic is our fight, flight, and freeze mode. The parasympathetic is the healthy, calm functioning mode. The vagus nerve is part of maintaining the balance between parasympathetic and sympathetic, and heart rate variability (HRV) is a measure of its functionality.
“Cardiac vagal tone, which represents the contribution of the parasympathetic nervous system to cardiac regulation, is acknowledged to be linked with many phenomena relevant for psychophysiological research, including self-regulation at the cognitive, emotional, social, and health levels. The ease of HRV collection and measurement coupled with the fact it is relatively affordable, non-invasive and pain free makes it widely accessible to many researchers.”Sylvain Laborde, Emma Mosley, and Julian F. Thayer. Heart Rate Variability and Cardiac Vagal Tone in Psychophysiological Research – Recommendations for Experiment Planning, Data Analysis, and Data Reporting. Front Psychol. 2017; 8: 213.
Published online 2017 Feb 20. doi: 10.3389/fpsyg.2017.00213
HRV isn’t only for researchers. Specialists who treat brain injury use it as a measure of cardiac function and treatment effectiveness. They also use HRV training prior to treatment as a way to rebalance towards the parasympathetic arm and help make treatment more doable and effective. It’s difficult to work on anything when your autonomic nervous system is in sympathetic mode and keeping you in fight, flight, or freeze mode.
“Particularly strong evidence indicates that childhood adversity and adulthood trauma exposure increase risk for physical and psychiatric disorders, and there is emerging evidence that inflammation may play a key role in these relationships.”Joy E Lin, Thomas C Neylan, Elissa Epel, and Aoife O’Donovan. Associations of childhood adversity and adulthood trauma with C-reactive protein: A cross-sectional population-based study. Brain Behav Immun. 53:105-112. Mar 2016. doi: 10.1016/j.bbi.2015.11.015. Epub 2015 Nov 23.
In addition, as I write in Emotional Trauma below, trauma that continues on after the brain injury can keep stoking neuroinflammation, making it harder to treat.
What Brain Injury Is Not
On 29 April 2013, Thomas Insel, then the Director of the National Institute of Mental Health in the USA, declared that the NIMH will be reorienting away from the traditional Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The NIMH essentially declared the categories of symptoms for brain issues no longer useful nor wanted. As Insel wrote, “symptom-based diagnosis, once common in other areas of medicine, has been largely replaced in the past half century as we have understood that symptoms alone rarely indicate the best choice of treatment.”
Of all the brain issues aka mental disorders, brain injury is the most obvious one that should not be seen as categories of symptoms. It should be seen as physical damage at both the brain and cellular levels that requires treatments in the same way damaged hearts or broken bones are treated.
“The diagnostic system has to be based on the emerging research data, not on the current symptom-based categories. Imagine deciding that EKGs were not useful because many patients with chest pain did not have EKG changes. That is what we have been doing for decades when we reject a biomarker because it does not detect a DSM category. We need to begin collecting the genetic, imaging, physiologic, and cognitive data to see how all the data – not just the symptoms – cluster and how these clusters relate to treatment response.”Thomas Insel. Transforming Diagnosis. 29 April 2013
Recovery Without Treatment Still Equals Higher Risk of Dementia
Even when it looks like a person has recovered spontaneously in the current wait-and-see approach, the risk of dementia remains elevated, and changes in attention, memory, anxiety, or depression don’t really go away. For example, elevated anxiety may play out like a person unable to sit down, which then becomes mistakenly ascribed as, “Oh, that’s just how they are.” Or they’re diagnosed with depression and the link to a “mild concussion” is dismissed or not even considered to be investigated, and they’re given anti-depressants to manage the symptom instead of treatment to heal the cause.
“Stevens, along with her mentor at Stanford, Ben Barres, had proposed that brain cells called microglia prune neuronal connections during embryonic and later development in response to a signal from a branch of the immune system known as the classical complement pathway. If a glitch in the complement system causes microglia to prune too many or too few connections, called synapses, they’d hypothesized, it could lead to both developmental and degenerative disorders.”Emily Underwood. This woman may know a secret to saving the brain’s synapses. Science. 18 Aug 2016.
Beth Stevens went on to prove her hypothesis correct, as written about in the excellent book The Angel and The Assassin. As outlined above, brain injury causes microglia to prune too much (or too little). Without intervention, degenerative disorders including dementia, will occur later in life. Only neurostimulation therapies have been shown to reboot this process back to health.
But this is what might be happening to microglia after a brain injury:
In this image above, traumatic brain injury creates amyloid beta proteins. (A) shows the TREM2 gene assisting in clearing out these proteins. (B) shows one possible effect of this gene being mutated is that cells can’t sense the proteins so don’t clear them out. (C) shows another possible effect is that other signals dominate that lead to microglia releasing cytokines and chemokines that lead to more proteins being produced.
Most Importantly Of All…
“Any deviation from the norm in delta, gamma, theta, and beta waves alerts practitioners…that these microglial-neuronal interactions are not functioning as they should.”Donna Jackson Nakazawa. The Angel and The Assassin. The tiny brain cell that changed the course of medicine. Random House. Ballantine Books. 21 Jan 2020.
Researchers in 2017 proposed that,
“[central nervous system] diseases be viewed as failed circuits caused in part by disease-specific dysfunction of cells traditionally called ‘glia’, and hence, favor therapies promoting their functional recovery.”Roser Masgrau, Carmen Guaza, Richard M Ransohoff, and Elena Galea. Should We Stop Saying ‘Glia’ and ‘Neuroinflammation’? Trends Mol Med. 23(6):486-500. Jun 2017. doi: 10.1016/j.molmed.2017.04.005. Epub 2017 May 9.
To see details on brain injury symptoms — what brain injury looks like outwardly — check out the rest of the tiles in the Education section.
Brain Injury Examples
Emotions Are Physical
“We are brothers and sisters under the skin with all other animals.”Primal Emotions — Affective Feelings from The Science of Emotions TEDxRainier talk by Jaak Panksepp
Why include social wounds and emotional trauma in injury list?
Because as Dr. Norman Doidge so comprehensively demonstrated in his book The Brain’s Way of Healing, anything and everything changes the brain. Also: human beings are social animals. We’re biologically designed to work together, to socialize, to be together. Add brain-controls-all with our social biology to emotional trauma and events that break social bonds and you have a damaged brain state.
Why Emotional Trauma Is Hard To Treat
I believe post-traumatic stress disorder (PTSD) is hard to treat because we’re not perceiving it as an injury that manifests physically in how neurons and neural networks change. It is. Chemical solutions won’t restore proper functioning, whatever the cause of brain injury. There’s a reason why talk therapy, especially dialectical behaviour therapy, helps. And touch is healing. They activate bonding neuroplasticity and re-establish healthy wiring that reflects a normal social bond where betrayal, emotional wounding, and abandonment don’t exist. They also push back neurally against the isolating rejections people with brain injury suffer after injury. But it’s insufficient in a continuing traumatic situation and certainly in brain injury from causes like stroke, concussion, epilepsy, and so on. In that case, one must stimulate the neurons towards harmony and a healthier wiring while using talk therapy concurrently to change thinking and emotions in sync with that neurostimulation.
“Ted Kaptchuk, head of Harvard Medical School’s Program in Placebo Studies and the Therapeutic Encounter, has shown that the placebo effect kicks in as a biological response to feeling cared for by one’s physician or healer, and increases with the quality and quantity of the patient-healer relationship.”Donna Jackson Nakazawa. The Angel and The Assassin. The tiny brain cell that changed the course of medicine. Random House. Ballantine Books. 21 Jan 2020.
That’s why therapy must be done daily because the emotional and/or social trauma is occurring daily, stoking neuroinflammation, and so the biological healing response must be commensurate. This ongoing trauma won’t change until society and individuals decide that brain injury isn’t synonymous with laziness, malingering, or bad attitude; until health care professionals recognize the benefits of neurostimulation therapies and provide them; and until governments fund these treatments and community care for as long as is needed to support restoration of health and functionality and recreating a role in society.
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Beth Stevens, Nicola J Allen, Luis E Vazquez, Gareth R Howell, Karen S Christopherson, Navid Nouri, Kristina D Micheva, Adrienne K Mehalow, Andrew D Huberman, Benjamin Stafford, Alexander Sher, Alan M Litke, John D Lambris, Stephen J Smith, Simon W M John, and Ben A Barres. The classical complement cascade mediates CNS synapse elimination. Cell. 131(6):1164-78. 14 Dec 2007. doi: 10.1016/j.cell.2007.10.036.
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Joy E Lin, Thomas C Neylan, Elissa Epel, and Aoife O’Donovan. Associations of childhood adversity and adulthood trauma with C-reactive protein: A cross-sectional population-based study. Brain Behav Immun. 53:105-112. Mar 2016. doi: 10.1016/j.bbi.2015.11.015. Epub 2015 Nov 23.
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Charles Raison and Vladimir Maletic. The New Mind-Body Science Of Depression. New York: WW Norton. 2017.
Helena Morrison, Kimberly Young, Mahir Qureshi, Rachel K. Rowe & Jonathan Lifshitz, Quantitative microglia analyses reveal diverse morphologic responses in the rat cortex after diffuse brain injury. Scientific Reports volume 7, Article number: 13211. 2017.
Gary Greenberg. What If the Placebo Effect Isn’t a Trick? New York Times Magazine. 7 Nov 2018.
Kathryn L. Wofford, David J. Loane, and D. Kacy Cullen. Acute drivers of neuroinflammation in traumatic brain injury. Neural Regen Res. 14(9): 1481–1489. Sep 2019. doi: 10.4103/1673-5374.255958
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Donna Jackson Nakazawa. The Angel and The Assassin. The tiny brain cell that changed the course of medicine. Random House. Ballantine Books. 21 Jan 2020.
Laura N. Verboon, Hiren C. Patel, and Andrew D. Greenhalgh. The Immune System’s Role in the Consequences of Mild Traumatic Brain Injury (Concussion). Front Immunol. 2021; 12: 620698. Published online 2021 Feb 15. doi: 10.3389/fimmu.2021.620698
“Schwann cells play a vital role in axon regeneration. Any injury to the axon can lead to cell death and axonal degeneration. Upon injury, Schwann cells and macrophages are recruited to the injury site to remove dead cells and promote axonal regeneration. Mechanistically, Schwann cells promote the recruitment of macrophages by inducing myelin breakdown and increasing the expression of cytokines, such as tumor necrosis factor-alpha. In addition, Schwann cells induce axon regeneration and nerve cell survival by increasing the expression of a wide variety of growth factors, such as neurotrophins, transforming growth factor-beta, glial cell line-derived neurotrophic factor, epidermal growth factors, and platelet-derived growth factor. They also secrete extracellular matrix molecules, such as laminin and collagen, and cell adhesion molecules to support the regeneration process. The axonal growth is guided by the cues provided by the lumen of the basal lamina of Schwann cells. “ https://www.news-medical.net/health/What-are-Schwann-Cells.aspx
“Motor neurons, which have processes that reside in both the CNS and the PNS, do regenerate, however. In the absence of intervention, motor neurons are one of the only CNS neurons to regenerate following axotomy.“ https://www.ncbi.nlm.nih.gov/books/NBK28000/
“Motor neurons (MNs) are neuronal cells located in the central nervous system (CNS) controlling a variety of downstream targets. There are two main types of MNs, (i) upper MNs that originate from the cerebral cortex and (ii) lower MNs that are located in the brainstem and spinal cord.“ https://www.frontiersin.org/articles/10.3389/fncel.2014.00293/full
Pyramidal cells “Like many other types of neuron, their main job is to transform synaptic inputs into a patterned output of action potentials” https://www.cell.com/current-biology/pdf/S0960-9822(11)01198-5.pdf