From the perspective of 20 19, it seems shocking that President Kennedy neglected the risk of brain injury related to exercise when promoting the benefits of exercise to brain health. However, in 1960, when he put forward a plan to improve the national physique in an all-round way, no one had noticed the adverse effects of sports-related head injuries on brain development and function. Even 45 years later, when the journal of neurosurgery reported. Mike Iron Man? Mike Webster's chronic traumatic encephalopathy (CTE), the adverse effects of sports-related head trauma are still largely unknown to the public, even if it is mild, it can be said that the medical community generally lacks understanding of it. It is worth noting that Webster himself has never been diagnosed with concussion or other forms of brain injury during his playing. Since then, people's attitudes have changed a lot, but how can we deepen our understanding of head trauma and its adverse effects? And the most important point is, how will our deepening knowledge guide the future road?
What is sports-related head injury?
In the process of exercise, brain injury is generally due to the rapid acceleration of the brain in the skull, which is sometimes called? Closed head injury? . When the head is hit, the external force makes the brain vibrate in the skull. According to Newton's third law of motion, the brain will first move to the impact point and then move in the opposite direction. However, more importantly, an off-center impact will inevitably produce a rotating force, which will lead to the distortion and stretching of the brain. It is worth noting that the impact of the head itself does not directly act on the brain tissue. Therefore, although helmets and pads can effectively prevent fractures and internal bleeding, they cannot protect the brain from damage caused by acceleration.
Brain trauma is generally classified according to the duration of coma caused by it. Teenagers' sports brain injury mostly belongs to mild brain injury, that is, no coma occurs at all or the coma time is less than 20 minutes. Concussion is synonymous with mild brain injury. Although diagnostic examination is not needed to detect sports concussion, some studies have applied brain imaging and other examination methods, and the results show that sports concussion will change the structure and function of the brain.
The degree of recovery and the final result after brain injury depend on many factors, such as age (young and old people are at higher risk) and gender (girls seem to be at higher risk). Some gene variants (such as apolipoprotein E-e4) increase the risk of adverse consequences after severe brain injury. The new research results show that this gene and other gene variants may also adversely affect the recovery of concussion. Many environmental factors that are not fully understood may also affect risks. For example, the advanced intellectual function before injury plays a protective role. After a sports-related concussion, the symptoms usually disappear completely soon. More than 95% of young athletes will recover within three months. If the symptoms persist for more than three months, it may be diagnosed as post-concussion syndrome. Drugs and other treatments can be used to treat the symptoms of sports concussion, but at present, drugs or biotherapy have not been found to prevent the development of symptoms or shorten the recovery time. We are still waiting to develop effective treatment methods, but a structured rehabilitation plan under the supervision of doctors, especially returning to the game in a safe situation, can maximize the chances of complete recovery.
During the competition of collision sports, the head will be hit many times, and these impacts do not show obvious signs or symptoms of brain damage. But what about these? Secondary concussion? The impact will still exert force on the brain and may induce subclinical pathological changes similar to obvious concussion. In fact, we found that sub-concussion may be related to brain symptoms that most athletes don't notice, and these symptoms can be found by careful inquiry. The impact under concussion is also related to the objective changes of brain function and microstructure, which can be detected by electroencephalography (EEG), magnetic resonance imaging (MRI) and formal cognitive and balance tests. In the life of athletes, the severity of repeated concussion is the focus of attention at present.
Hitting the head may lead to serious acute injuries, such as skull fracture and hematoma. Hematoma may occur in epidural space (bleeding between skull and meninges) or subdural space (bleeding between meninges and brain surface). Brain tissue bleeding may be caused by tissue or blood vessel tearing. In early American football (before the introduction of helmets), the death caused by these serious injuries was a major problem, but it was very rare in modern collision sports. Helmets, padded helmets and goalposts are all padded, which can reduce the severity of impact force by dispersing it over a large surface area, thus reducing the risk of complications, such as skull fracture and epidural or subdural hematoma. However, the protective headgear can not alleviate the brain injury caused by the acceleration of intracranial brain tissue.
Deepen our understanding of brain injury
The human brain is a delicate and complicated information processing system. In the soft gelatinous fresh brain of about 1400g, there are 1000 billion neurons, and each neuron sends out an axon, which is a filiform process up to one meter long, and sends electrochemical information to nearby neurons and spinal cord. Axons are only one-tenth the diameter of red blood cells. Axons form the network circuit of the brain, and transmit information through as many as 400 billion network connections (called synapses), so that neurons can process information together. It is worth noting that the brain cannot switch to the mode of wireless network to work; We completely rely on its physical network to achieve simple functions, such as sports, and those complex behaviors that embody our humanity, such as remembering, imagining, planning the future, controlling behavioral impulses, etc., need to rely on this physical network even more. The latter function needs to process information in a widely distributed brain network. When the network is destroyed, both simple and complex functions will be adversely affected.
The complexity of brain structure and function is unique in all organs and tissues of human body, so it is particularly fragile. When the head is hit, the head accelerates sharply, and the soft brain moves in the skull and is compressed, stretched and twisted. In some ways, the brain is very tolerant of these forces. For example, bleeding is not common. Nevertheless, linear and rotational forces spread through the brain, leading to axonal injury, which is called traumatic axonal injury. This type of injury is the pathological basis of temporary and permanent brain network dysfunction and subsequent functional problems after head trauma.
When the brain vibrates in the skull after being hit, we may expect that the fragile axon will be torn, resulting in the immediate interruption of network traffic and loss of function. When trauma occurs, we may expect to show the greatest functional effect. But strangely, this is not the case. The degree of head trauma caused by collision, fall or heading during exercise is unlikely to directly cause tissue or axon tearing. Therefore, sports-related head injuries, including sports-related concussion, rarely have obvious clinical imaging manifestations like cerebral hemorrhage. On the contrary, the strain on the axon will trigger a series of molecular and cellular events, which may lead to its dysfunction and eventually degeneration. Eventually, the resulting damage impairs brain function.
A series of reactions caused by brain trauma, first of all, axonal subcellular components (such as axonal membrane, that is, axonal membrane) are subjected to mechanical stress, and finally a toxic microenvironment is produced, leading to further damage. Mechanical stimulation causes dysfunction, neuron depolarization (cell surface charge transfer), excessive release of excitatory neurotransmitter glutamate, and imbalance of sodium (Na) and potassium (K) ions in neurons. Excessive release of glutamate will activate the n- methyl aspartic acid (NMDA) receptor on brain cells, which will adversely affect the cell pump that maintains the intracellular Na/K balance. Excitative toxicity, these receptors over-activate toxic substances such as glutamic acid and NMDA, which leads to further ion imbalance and accumulation of metabolites in neurons, especially calcium ion chelation, and further contributes to toxic microenvironment.
Toxic microenvironment leads to various secondary cellular effects, causing further damage. An example of secondary injury is the activation of brain immune cells, such as microglia and astrocytes. The impact of experimental mice on cerebral cortex under controlled conditions is a serious brain injury model, and the result is the induced release of amino acid D- serine. D- serine binds to NMDA receptor, resulting in synaptic damage. Synapse is the connection point between brain cells. In this animal model, blocking the release of D- serine plays a protective role. Long-term and persistent adverse cellular reactions and decreased axonal transport are considered as another injury mechanism. Reduce the elimination of metabolites through the brain sugar gland system, and aggravate the toxicity of microenvironment and toxins (such as hyperphosphorylation? Protein)] accumulation. In chronic traumatic encephalopathy and other neurodegenerative diseases, nerve fiber nodules formed by pTau have been found, especially around small blood vessels in the brain, which is thought to lead to cell death.
In recent years, a lot of knowledge about the molecular and cellular mechanisms of brain injury has been accumulated, most of which are based on experimental research. However, these studies all use quite serious injury models, which are very different from the injuries that usually occur in sports. Another important constraint to our understanding of clinical phenomena is that we cannot directly observe the mechanism of human brain injury in vivo. Recently, however, the use of radiolabeled pTau antibodies has enabled us to use positron emission tomography (PET) for in vivo detection. PTau-PET technology brings great hope for directly detecting the long-term injury caused by repeated head impact in vivo, but it is still in the early stage of development and has not yet entered clinical application. Until clinical trials are verified and widely used, it is impossible to know the true incidence and influence of pTau deposition and other damage phenomena.
Excitative toxicity, neuroinflammation caused by head trauma, the degree of toxic microenvironment, the time course of its evolution and the degree of improvement or persistence determine whether the wounded will be adversely affected for a long time. In this regard, the cascade evolution mechanism of injury with time may be the key to effective treatment of brain injury. Adverse molecular processes can be shut down by targeting and inhibiting damage mechanisms, so that they can be shut down before causing damage. To achieve this goal, it is necessary to identify the damage, understand the time process of the damage, and carry out targeted and accurate intervention in time.
During the competition of collision sports, the head will be hit many times, and these impacts do not show obvious signs or symptoms of brain damage. But what about these? Secondary concussion? The impact will still exert force on the brain and may induce subclinical pathological changes similar to obvious concussion. In fact, we found that sub-concussion may be related to brain symptoms that most athletes don't notice, and these symptoms can be found by careful inquiry. The impact under concussion is also related to the objective changes of brain function and microstructure, which can be detected by electroencephalography (EEG), magnetic resonance imaging (MRI) and formal cognitive and balance tests. In the life of athletes, the severity of repeated concussion is the focus of attention at present.
It is beneficial to compare brain trauma with other common injuries. Fracture or muscle tear occurs and is completed at the time of trauma. Then, the body begins to repair the damage. When the liver is damaged in a motor vehicle collision, new functional liver tissue will regenerate. But as mentioned above, brain injury is a process caused by trauma, which evolves with time. If not controlled, the lesion may be irreversible. Fortunately, for most athletes with head injuries, after a single head injury, the symptoms will disappear quickly within minutes to weeks. When the above-mentioned bad molecular and cellular reaction cascade subsides before the axon is permanently damaged, it is possible to recover. But once the axon degenerates, it can neither be repaired nor regenerated or replaced. Injury background, congenital factors and environmental factors may be very important for understanding the time course and recovery degree of brain injury. But we are just beginning to understand the relevant details, which is the focus of in-depth research at present.