The severity of concussion may depend on DNA

Neuropathologists Lili Naz Hazrati and Nicole Schwab explain why different people have different possibilities for neurodegenerative diseases after concussion in the context of genetic diversity The results were recently published in the open access journal Acta neuropathologica communications About 10 million people suffer from traumatic brain injury (TBI) every year, most of them are mild TBIs Often referred to as concussion, mTBIs can sometimes cause a range of symptoms, including headaches, fatigue, anxiety, depression, and difficulties in memory and attention Continuous exposure to concussion will increase the risk of neurodegenerative disease in the future, but this is not the inevitable outcome of all patients with concussion It's not clear how concussions cause symptoms, or why some people are more vulnerable or resistant to concussions Changes in cell levels in the brain with a history of concussion in a study published in Acta neuropathica communications on November 14, 2019, we analyzed 38 brain donors who had a long history of mild concussion due to their involvement in contact sports such as football, hockey, rugby and boxing Our evidence suggests that there are inefficient DNA damage repair and cell aging (i.e., normal cell division stops irreversibly), which may be the pathophysiological mechanism of brain dysfunction after MTBI We think this phenomenon can explain why some people are more vulnerable to or resistant to concussion than others We evaluated the extent of DNA damage, immunohistochemical markers of cell aging, and gene expression in these brains Compared with healthy participants of the same age, the extent of DNA damage in TBI brain was significantly increased In the brain with a history of concussion, the expression of key DNA damage repair enzymes including breast cancer susceptibility type 1 (BRCA1) protein decreased significantly According to the above results, we believe that in the brain with a history of concussion, the repair mechanism of DNA is inefficient, which leads to the accumulation of DNA damage in the brain In addition to the changes in DNA damage and DNA repair ability, we also found that the brain with a history of MTBI has the characteristic of cell aging, namely, the permanent stagnation of cell cycle, which is characterized by chronic inflammation and genomic instability caused by DNA damage This stagnation of cell cycle leads to the decline of cognitive function, neurodegenerative diseases and aging and other symptoms In our study, the brain of MTBI showed astrocytes (a kind of astrocytes in the central nervous system) swelling and the absence of specific nuclear membrane proteins All these changes are the characteristics of cell aging, which is associated with genotoxic stress and changes in gene expression patterns In fact, by analyzing gene expression, we found a significant increase in gene expression related to cell cycle arrest, signal transduction of senescent cells and known proinflammatory factors secreted by senescent cells Taken together, these results suggest that cellular senescence occurs in the brain with a history of MTBI The study of DNA loss and cell aging in patients with concussion shows that the history of chronic concussion is related to the decreased expression of DNA repair enzyme, the increased burden of DNA damage and the markers of cell aging This shows that the recovery of patients with concussion depends on their ability to repair DNA damage effectively It is important that many DNA repair enzymes are polymorphic, which means they are genetically variable and have different expression patterns among different individuals Taking BRCA1 as an example, it has been proved that the point mutation in BRCA1 gene will increase the risk of breast cancer Similarly, different expression patterns of DNA repair genes (such as BRCA1) may make some people more susceptible to concussion due to the existence of ineffective DNA repair mechanisms in the brain By extension, some people may also be able to better resist the effects of head trauma due to the existence of too effective DNA repair mechanism in the brain Although we do not fully understand the mechanism of DNA damage and cell aging on the consequences of concussion, we believe that these results may vary from person to person Therefore, the pathophysiology of concussion is a complex problem to be solved, because everyone may show different molecular reactions to the same injury This means that in sports, we may not be able to implement the "one size fits all" policy, in the prevention and treatment of traumatic brain injury, we need to meet the needs of every individual (BIOON Com)