Will Smith's film concussion effect, tells the story of the Nigerian pathological anatomy doctor Bennett Oamaru accidentally discovered that the brain tissue of a retired rugby player after suicide was peculiar The changes of chronic sexual trauma have been verified by four cases, and the research results have been published in neurology professional journals. The article aroused the attention and hostility of the NFL, in parallel with the media and the government to suppress Bennett. A few years later, the suicide and suicide note of another famous football player finally rectified Dr. Bennett's research results, and the NFL easily settled a joint lawsuit of 5,000 people through economic means.
Maybe we still can't eliminate the injustices in life, and still can't fight against the arrogance of power, but we can at least understand some real medical knowledge and protect ourselves and our family as much as possible.
The chronic traumatic encephalopathy involved in the movie, English chronic traumatic encephalopathy, or CTE for short, is a progressive degenerative disease of the brain accompanied by symptoms such as memory decline, depression, and dementia. It mostly occurs in athletes with head injuries. It is easy to understand that rugby, boxing, ice hockey, and football are all prone to happen. But the project with the highest occurrence rate is certainly not what you would think of, it is actually horse racing.
In fact, as early as 1928, a pathologist named Martland published a paper reporting a group of similar cases of boxers. Of course, the name at the time was not CTE, but "punch drunk syndrome" (punch drunk syndrome). In 1969, Roberts conducted a comparatively scientific and systematic study. He randomly selected 250 of 16,781 boxers. As a result, 35 of them had neurological damage, accounting for 17%. In 1973, Dr. Corsellis published the results of a pathological study of the brain tissues of 12 boxers, clarifying the pathological changes in the brain tissues. At the same time and the following decades, there are a large number of CTE clinical and pathological studies on boxers. In addition to occupational factors, genetic factors are also predisposing factors for CTE. Then it was the turn of the two papers by Dr. Bennet in the movie. In fact, from 2002 to 2007, there were several reports on the CTE of NFL athletes. Later, in Waltham, Massachusetts, the Center for Brain Trauma Research (CSTE, hereinafter referred to as the "Brain Injury Center") was jointly established by the Boston University School of Medicine and the non-profit organization "Sequences of Exercise Institute". Therefore, after a series of studies on the remains donated by the families of athletes, they also targeted chronic traumatic encephalopathy (CTE) as the culprit behind the scenes.
How does chronic traumatic encephalopathy harm the health of athletes? Professor Robert Cantu and other brain trauma center experts used MRI technology to observe the brains of several deceased athletes suffering from chronic traumatic encephalopathy. "An important clue is the Tau protein distributed near the central nervous system. Their role is to support the microtubules that transfer molecules between neurons and cells." Robert Cantu explained, "If the brain is subjected to frequent external impacts, it will The microtubules in the impacted area are deformed and eventually collapsed, thereby forcing neurons and cells to lose their normal function, while Tau protein will accumulate in the damaged area. If we compare a group of healthy people’s brain scans with patients Comparing, it is easy to see that the number of microtubules in the brain area imaging of the latter is significantly reduced, and there is a large amount of abnormal Tau protein accumulation, presenting a dark brown area with clear edges." It was not until 2015 that the academic community was right. A consensus was reached on the pathological features of CTE in the autopsy brain tissue. Eight neuropathologists collectively performed a double-blind diagnosis and analysis on the brain imaging data of multiple patients with neurodegenerative diseases (including Alzheimer's and suspected CTE). The results showed that compared with other neurodegenerative diseases, CTE has two characteristic changes: tau protein sequestration in neurons around cerebral blood vessels, and tau protein accumulation in cells at the bottom of the brain sulcus. The results will be released at the American Neuroscience Conference this week. This is the first time that CTE is clearly defined as an independent pathological disease.
Small et al. of the University of California, Los Angeles (UCLA) also observed a similar phenomenon (tau protein accumulation and deposition) in patients through a "non-invasive" technique. A number of research reports, including those published in the Proceedings of the National Academy of Sciences (PNAS) on April 6, stated that a tau-sensitive brain imaging agent FDDNP was injected into several former NFL athletes (originally used to observe Alzheimer’s Abnormal deposition of β-amyloid protein in the brain of patients with severe disease) After PET scan, it was found that, similar to the pathological results, the patient’s brain will show tau and amyloid deposition, which is similar to Alzheimer’s and other neurodegenerative patients. There are significant differences between.
However, Stern expressed doubts about the above results. He believes that the area marked by FDDNP is not consistent with the pathological results. In addition, Patrick Bellgowan, project leader of the National Institute of Neurological Disorders and Stroke (NIN-DS), said that FDDNP can bind to a variety of brain substances and cannot specifically label tau protein. But the UCLA research team insisted that FDDNP does not need to specifically bind to tau protein to distinguish CTE from other neurodegenerative diseases.
Despite the difficulties of CTE research, Stern is optimistic. He found that the compound T807 can specifically bind to tau more specifically than FDDNP, and can obtain imaging results similar to autopsy results. Stern mentioned in the witness oath in the "American Football Retired Athlete Lawsuit" that he believes that an FDA-approved technical method for in vivo diagnosis of CTE will surely emerge within 5 to 10 years.
How can athletes be effectively protected from external brain injuries? "Strengthen protection" seems to be the most logical answer. The helmets worn by early football players were modified from the equipment of motorcyclists and pilots. They were made of thick leather. Holes were cut in the ear protectors to facilitate communication between the players and their teammates on the field. It was not until the late 1930s that some sports product manufacturers began to consider adding foam padding to the helmet to further absorb the impact of the athlete’s head. In 2009, Riddell, a well-known sports equipment manufacturer, conducted a three-year study at the University of Pittsburgh School of Medicine and launched a new generation of ice hockey and football helmet "revolution"-it adopted a brand-new polycarbonate material and foam The inner lining extends the dome of the helmet body and strengthens the protection of the player's jaw. Athletes wearing "revolutionary" new protective helmets have an annual concussion probability of 5.3%, which is 2.1% less than the control group equipped with traditional helmets. However, on the whole, the "revolution" is not much different from the predecessor product that Gerald Ford refused to wear 70 years ago. The more radical design comes from the XenithX1 designed by former Harvard University quarterback Fin Ferrana. It completely abandons the foamed lining protection and uses a self-developed "shock absorption system", which is based on carbon fiber and polyester materials. Between the inner and outer layers of the helmet, there are 18 hollow thermoplastic "shock absorbers" whose shapes are like stubby cylinders and are irregularly distributed based on the principles of human mechanics. Like the Shox shock absorption technology developed by Nike 10 years ago, when an athlete encounters a head impact, the external impact energy is effectively absorbed by these cylinders.
So far, there is no definitive treatment for CTE. The following will describe a hypothesis for the first time: lithium, at standard or even lower doses, can improve or prevent CTE from the above three aspects, including the prevention of suicide and dementia.
Suicide prevention
lithium is the only proven suicide prevention drug in the psychiatric literature. In the past few decades, tens of thousands of people have studied the drug in randomized clinical trials, and the researchers compared these trial data with placebo in a meta-analysis. The effect of lithium is large, it reduces the risk of suicide by 87% (OR 0.13; 95% CI 0.03-0.66). Evidence-based medicine points out that lithium can prevent suicide. In addition, there is no relevant confirmation that other drugs can prevent suicide.
A study on the antipsychotic drug clozapine, can reduce suicide attempts in randomized clinical trials, no suicidal behavior occurred. In other words, it cannot be proven that clozapine can prevent suicide.
As we all know, depression may be the most important risk factor for suicide. It is also a well-known controversy that the most widely used class of drugs, serotonin reuptake inhibitors (SRIs), can be used to treat depression while preventing or even causing suicide. Obviously, there is no evidence that SRIs have no effect on suicide prevention. Therefore, so is the claim that lithium is the only proven suicide prevention drug in psychiatry.
In the aforementioned randomized clinical trials, patients with mental illnesses such as unipolar depression and bipolar disorder (mainly the latter) were given lithium at a standard dose (usually about 600 to 1200 mg/d). In addition to the data from these randomized clinical trials, a large number of epidemiological literature confirms that lithium can prevent the suicide of patients with mental illness, even for the general population without mental illness. These studies are based on an analysis of the population of an area, and there is a "high" level of natural lithium in the geology of the area. Lithium is a metal element, found in rocks and in the earth's crust and water sources. It is first absorbed by vegetables and then by animals. Lithium is a rare metal, and lithium is also present in the human body. The normal content of lithium in the human diet is about 1 mg/d. The content of lithium in a high-lithium diet is more, such as 5mg/d. The "low" lithium diet contains very little lithium, less than 1 mg/d, or even no lithium at all. Numerous epidemiological studies in different countries have found that the suicide rate of residents in "high-lithium" areas is lower than that of "low-lithium" areas.
If, as shown by the results of randomized clinical trials, lithium can prevent the suicidal behavior of patients with mental illness; if, as the results of epidemiological and geological studies, low-dose lithium can also prevent ordinary people without mental illness from committing suicide, then low-dose Lithium may prevent CTE patients from committing suicide. These people have emotional symptoms, but in a strict sense, there is no mental illness dominated by unipolar depression or bipolar disorder. In order to reduce the side effects and toxicity of lithium, low-dose lithium is used for CTE patients. The treatment may work.
Prevent Alzheimer's Disease
Numerous animal and human studies have confirmed that lithium can protect nerves and prolong the lifespan of neurons. Lithium not only acts on the brain, it may also have a positive effect on cognitive impairment and even Alzheimer's disease. This hypothesis has been supported by many studies on mental illness.
The longest and largest prospective cohort study of mental illness conducted by Jules Angst of Zurich and his colleagues found that 406 patients with unipolar depression or bipolar disorder had a very high rate of dementia. The follow-up of these patients began in the 1960s, and the follow-up of these subjects continued until they died. The results found that the prevalence of Alzheimer's disease in the 65-68-year-old survey group was 22%, which was an ordinary person of the same age. Four times the prevalence. Researchers found that compared with other drugs (including antidepressants and antipsychotics), the incidence of dementia in patients treated with lithium was reduced by 87% (OR 0.23; 95% CI 0.06 to 0.89). In other words, lithium reduces the prevalence of Alzheimer's disease to an average level.
Many epidemiological studies of lithium in the treatment of bipolar disorder have reported such results. Most of the cohort studies confirmed the results of the Zurich cohort study. Most of the studies are cross-sectional studies or retrospective studies; therefore, the results of the Zurich cohort are by far the most valid and accurate data on this topic.
Based on the above-mentioned research, some researchers have begun to think and study lithium treatment of Alzheimer's disease. An initial small randomized trial study showed that lithium had no effect on biomarkers of Alzheimer’s, but the study was too small or too short to test whether lithium can change the course of early Alzheimer’s. Three other randomized trials have been conducted, and the results have shown that compared with placebo, lithium is effective in reducing the severity and progression of Alzheimer's disease.
If lithium can not only treat the symptoms of dementia in patients with bipolar disorder, but also the symptoms of dementia in patients with various other mental disorders, lithium can effectively prevent CTE patients from developing dementia.
Treat emotions and impulses
As we all know, the effect of lithium on mood symptoms is to treat depression and mania. Standard texts in the field, such as bipolar disorder, provide clear scientific support for these effects. Another effect-lithium seems to improve the impulsive behavior of patients with mental illness or even normal people, this effect is sometimes not well noticed. The latter effect has been reported in many clinical studies of psychiatric diseases (traumatic brain injury TBI). We reviewed the literature about lithium on TBI. In addition to some clinical reports, a well-known animal study found that lithium is helpful for TBI in neurobiology. Compared with animals that did not receive lithium treatment, the injured neurons of the animals that received lithium repaired and recovered more completely. Considering the effects of lithium on the brain in the extensive neuroscience literature, this effect is not surprising.
Get rid of tau protein The
scientific literature has well reviewed the effects of lithium on the brain, including increasing the activity of neuroprotective proteins such as brain-derived neurotrophic factor (BDNF), GSK-3, and blocking harmful proteins such as BCL-2. GSK-3, an important factor in the development of tau protein, has been identified as the main abnormal factor in CTE neuropathology. There are protein lesions in CTE patients, so the brain is full of this harmful protein. Animal studies have shown that through the effect of lithium on GSK-3 and other possible mechanisms, it hinders the development and accumulation of tau protein.
In short, lithium can treat or prevent CTE, including helping to treat depression and impulsivity, but also to prevent suicide and dementia. This hypothesis is reasonable and supported by the clinical scientific literature. The public, researchers, and head trauma personnel should pay more attention to this potential treatment.
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