Category: Injury & Trauma

New Insights into First Stages of Wound Healing

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Photo by cottonbro from Pexels

A new study from Vanderbilt University researchers has revealed how cells detect and react to wounds.

The epithelial cells which cover the body and its organs, must be able to heal wounds, as they are constantly exposed to insults and abrasion. “When these cells detect a wound nearby, they change their behaviours,” said study co-leader Professor Andrea Page-McCaw in the Department of Cell and Developmental Biology. “They transition from stationary, nondividing, noninvasive cells to cells that migrate, divide and invade.” This also describes the behaviors of cancer cells, which adopt wound-healing behaviours without any wound.

The researchers began with focusing on epithelial cells’ first known reaction of to a nearby wound: an increase in calcium levels, which typically occurs within a minute of wounding.

“We were able to connect the response of these cells directly to the cellular damage inherent in wounding,” Prof Page-McCaw said. “We found that wounds destroy cells, causing them to leak or even burst, and some of their contents get out. Outside of cells, tissues have a detector molecule ready to sense these cellular contents. When they do, proteases in the cellular contents chop up the detector molecule into smaller pieces, which spread to nearby cells. This activates receptors on the cells’ surfaces, giving them the information that a wound is nearby.”

Successful and efficient wound healing is key for recovery from trauma or surgery, and this study improves the understanding of how wounds are recognised by epithelial cells and how this leads to wound healing. This will help develop therapeutics that can address this health issue.

Slow wound healing time can be caused by a number of factors, such as diabetes, and can lead to infection and declining health. By figuring out how to downregulate these wound-healing behaviours in combination with other cancer interventions, this work offers insights that could help combat cancer’s adoption of this mechanism.

The researchers will next focus on how cells use the information they receive about the presence of a wound, specifically how the information is encoded in the calcium signal dynamics and then converted into migration, proliferation and changes in cell- and tissue-level mechanics. “Now that we have a solid understanding of how the presence of a wound is first signaled to nearby cells, we can ask a lot of interesting follow-up questions,” said study co-leader Shane Hutson, chair of the Department of Physics and Astronomy and professor of physics and biological sciences. “How much information is present in those signals? Can cells interpret the signals to know how large the wound is or how far they are from the wound? Do they use the way the dynamic signals change with time to make that measurement? What are the detailed mechanisms by which the signals then get turned into cellular actions?”

Source: Vanderbilt University

Journal information: James T. O’Connor et al, Proteolytic activation of Growth-blocking peptides triggers calcium responses through the GPCR Mthl10 during epithelial wound detection, Developmental Cell (2021). DOI: 10.1016/j.devcel.2021.06.020

New Wound Healing Scoring System Proposed

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Researchers have proposed a new scoring system for wound healing in mice based on parameters in each phase of healing.

The researchers described the system in an article in the peer-reviewed journal Stem Cells and Development.

Wound healing processes consist of a sequence of molecular and cellular events which occur after the onset of a tissue lesion in order to restore the damaged tissue. In order to evaluate the efficacy of new treatments, there is a need to monitor wound progression accurately and reproducibly over time. 

The parameters include re-epithelisation, epithelial thickness index, keratinisation, granulation tissue thickness, remodeling, and the scar elevation index. These parameters can be assessed using either Hematoxylin & Eosin or Masson’s Trichrome staining. Mari van de Vyver, from Stellenbosch University, and colleagues developed this histology scoring system for cutaneous wounds in mice. They then validated the system in four different types of murine skin wound models.

“This histological scoring system defines and describes the minimum recommended criteria for assessing wound healing dynamics,” state the authors. “The experience and ability of investigators to accurately identify structures in histology slides at different stages of healing is crucial for consistency and repeatability of measures to deliver meaningful results.”

“The development and validation of this scoring system in a randomized blinded investigation by researchers from Stellenbosch University (South Africa), Polish Academy of Sciences in Olsztyn (Poland), University of Texas Southwestern Medical Center (Texas, USA) and Obatala Sciences Inc. (New Orleans, USA) represents a truly international effort to advance the robust and accurate assessment of wound healing,” stated Graham C Parker, PhD, Editor-in-Chief of Stem Cells and Development and The Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI.

Source: Mary Ann Liebert, Inc.

Journal information: van de Vyver, M., et al. (2021) Histology Scoring System for Murine Cutaneous Wounds. Stem Cells and Development.doi.org/10.1089/scd.2021.0124.

Good Outcomes for Severe Brain Injury Still Possible

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A new study adds to the growing body of evidence that decisions regarding moderate-to-severe traumatic brain injury (TBI) should not be made too soon after the injury, as a good prognosis can still emerge.

Researchers followed 484 patients with moderate-to-severe TBI and found that among the patients in a vegetative state, one quarter “regained orientation” — awareness of who, when and where they were —  within 12 months of their injury.

“Withdrawal of life-sustaining treatment based on early prediction of poor outcome accounts for most deaths in patients hospitalised with severe TBI,” said senior author Geoffrey Manley, MD, PhD,  noting that 64 of the 92 fatalities in the study occurred within two weeks of injury. Dr Manley is professor and vice chair of neurological surgery at UCSF and chief of neurosurgery at Zuckerberg San Francisco General Hospital.

“TBI is a life-changing event that can produce significant, lasting disability, and there are cases when it is very clear early on that a patient will not recover,” he said. “But results from this study show a significant proportion of our participants experienced major improvements in life functioning, with many regaining independence between two weeks and 12 months after injury.”

The patients in the study were enrolled by the brain injury research initiative TRACK-TBI, of which Dr Manley is the principal investigator. All patients were 17 and older and had presented to hospitals with level 1 trauma centers within 24 hours of injury. Their exams met criteria for either moderate TBI or severe TBI. The causes were falls, assault and primarily crashes involving a motor vehicle.

The patients, whose average ages were 35 in the severe TBI group (78 percent males) and 38 in the moderate TBI group (80 percent males), were assessed using the Glasgow Outcomes Scale Extended (GOSE), which ranges from 1 for death to 8 for “upper good recovery” and resumption of normal life. Impairment was also categorised with the Disability Rating Scale (DRS).

At two weeks post-injury, 93 percent of the severe TBI group and 79 percent of the moderate TBI group had moderate-to-severe disability, according to the DRS, and 80 percent had GOSE scores from 2 to 3, meaning they required assistance in basic everyday functioning.

But by 12 months, half of the severe TBI group and three-quarters of the moderate TBI group had GOSE scores of at least 4, indicating they could function independently at home for at least eight hours per day. Moreover, 19 percent of the severe TBI group had no disability, according to the DRS, and a further 14 percent had only mild injury, the researchers noted.

Most surprising were the findings for the 62 surviving patients who had been in a vegetative state. By the 12-month mark all patients had recovered consciousness and 1 in 4 had regained orientation. All but one survivor in this group recovered at least basic communication ability.

“These patients made the cut for favorable outcome,” said co-first author, Joseph Giacino, PhD, of Spaulding Rehabilitation Hospital, Massachusetts General Hospital and Harvard Medical School. “Their GOSE scores were 4 or higher, which meant they could be at home unsupervised for at least eight hours a day, since they were able to take care of basic needs, such as eating and toileting.”

In prior work, a significant percentage of patients with grave impairments had been shown to achieve favorable functionality after many months or years. This study coincided with the recommendation in 2018 from the American Academy of Neurology that in the first 28 days after injury, clinicians should refrain from telling families that a patient’s prognosis is beyond hope.

“While a substantial proportion of patients die or suffer lasting disability, our study adds to growing evidence that severe acute impairment does not portend uniformly poor long-term outcome,” said Manley, who is also affiliated with the UCSF Weill Institute for Neurosciences. “Even those patients in a vegetative state – an outcome viewed as dire – may improve, since this is a dynamic condition that evolves over the first year.”

Source: University of California, San Francisco

Journal information:JAMA Neurology (2021). DOI: 10.1001/jamaneurol.2021.2043

CT Scans Improve Outcomes for Concussion Patients

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A study found that CT scans for concussion patients provide crucial information on their risk for long-term impairment and their potential to make a complete recovery, and points to the need for more follow-up.

In the UC San Francisco-led study, researchers examined CT scans of 1935 patients, aged 17 and over, whose neurological exams met criteria for concussion, or mild traumatic brain injury (TBI). Outcomes for moderate and severe TBI have been linked to CT imaging features, but this may be the first time this link has been identified in patients with concussion. This contradicts previous research which had found no prognostic significance of specific types of CT abnormalities.

“Radiologists who routinely read trauma scans know intuitively that patterns of intracranial injury on CT are not random,” said first author Esther Yuh, MD, PhD, of the UCSF Department of Radiology and Biomedical Imaging. “We showed there are patterns of injury, that some of these are associated with worse outcome than others, and that they provide a window into mechanisms of injury that is reproducible across large studies.”

The study was published online in JAMA Neurology.

“Although concussions are referred to as mild traumatic brain injuries, there is nothing mild about some concussions,” explained senior author Geoffrey Manley, MD, PhD, professor and vice chair of neurological surgery at UCSF and chief of neurosurgery at Zuckerberg San Francisco General Hospital. “Patients with concussion may suffer from prolonged headache, poor sleep and impaired concentration, and they are at higher risk of self-medicating with drugs and alcohol. Concussion can also contribute to depression and anxiety, and increase the risk for suicide. We need to view concussion not as an event but as a disease requiring physician follow-up after a patient is discharged from the hospital.”

The participants were enrolled by the brain injury research initiative TRACK-TBI, of which Manley is the principal investigator. To enrich the number of so-called complicated concussions, the researchers drew exclusively from patients who had been seen at hospitals with level 1 trauma centres. This meant 37 percent of study participants had a positive CT, significantly more than the 9 percent of positive CTs from patients in US emergency departments.

The most common patterns of injury, affecting more than half of CT-positive patients, were combinations of subarachnoid haemorrhage (SAH), subdural haematoma (SDH), and/or contusion, which may be caused by injuries such as falls from standing. About 7 percent had intraventricular haemorrhage (IVH) or petechial haemorrhage, caused by head rotation as in some sporting, scooter and automobile accidents; and 5 percent had epidural haematoma (EDH), often seen in sports injuries such as being hit with a baseball.

Average age of the patients was 41 and 66 percent were male. They were followed-up at two weeks, and at three-, six- and 12 months following injury. Patients in the SAH/SDH/contusion group failed to make a complete recovery at 12 months post-injury and had a range of outcome impairments, from mild to more severe.

Patients in the IVH/petechial haemorrhage group tended toward more severe impairments, in the lower-moderate disability range, a level potentially affecting multiple areas of function, such as employment, social and leisure activities, up to 12 months post-injury. Patients with EDH fared significantly better and demonstrated complete recovery by their six-month assessment.

Results from CENTER-TBI, a parallel brain injury research group that had enrolled 2594 participants at European trauma centres. validated the findings. “The confirmation of the findings in an independent cohort confirms the fidelity of our results,” said Manley, adding that patients with EDH were one exception, with incomplete recovery lingering for months longer than those patients followed by TRACK-TBI. However, more severe outcomes were not seen at any point in either study.

The researchers noted that even among concussion patients with positive CT scans, only 39 percent get follow-up care, which should be routine. They also cautioned that their findings are not a call for increased CT use, which has radiation dose concerns and is restricted to known or suspected concussions.

Indeed, a recently approved rapid hand-held blood test may reduce the amount of CT scans. Manley found this test was more sensitive than CT in detecting concussion. The blood test measures biomarkers associated with TBI, which were nearly 52 times higher in MRI-identified concussion patients than in healthy participants.

In addition to challenging the belief that CT features in concussion are not relevant, the researchers are also challenging the idea that concussion is “what the patient brings to the injury,” said Manley, who is also affiliated with the UCSF Weill Institute for Neurosciences. “In moderate and severe TBI, it is anecdotally taught that outcome is determined by ‘what the injury brings to the patient,’ while concussion is determined by baseline characteristics like age, sex and years of education. While the study confirms the importance of these characteristics, we show that in some concussion cases, poor outcomes are also attributed to ‘what the injury brings to the patient.'”

Source: University of California, San Francisco

Journal information: Yuh EL et al., Pathological computed tomography features associated with adverse outcomes after mild traumatic brain injury, JAMA Neurology, July 19, 2021.

New Biomarker for Soft Tissue Infections

This illustration depicted a three-dimensional (3D), computer-generated image, of a group of Gram-positive, Streptococcus pneumoniae bacteria. The artistic recreation was based upon scanning electron microscopic (SEM) imagery. Photo by CDC on Unsplash
This illustration depicted a three-dimensional (3D), computer-generated image, of a group of Gram-positive, Streptococcus pneumoniae bacteria. The artistic recreation was based upon scanning electron microscopic (SEM) imagery. Image by CDC on Unsplash

Researchers have identified a new and very promising biomarker for bacterial soft tissue infections, which previously lacked one. 

In bacterial soft tissue infections, rapid diagnosis is crucial in reducing the risk of severe injury or amputation. Vague symptoms and a varied patient presentations increase the risk of misdiagnosis.The study, by  Researchers at Karolinska Institutet in Sweden  and other research institutions, and published in the Journal of Clinical Investigation, may have implications for both diagnosis and treatment.

Last author Anna Norrby-Teglund, Professor, Department of Medicine, Karolinska Institutet, said: “There are currently no tools for safe, rapid diagnosis in life-threatening soft tissue infections. Our findings are consequently very interesting as the biomarkers identified are possible candidates for improved diagnostics. The results are also relevant for individualised treatment in the future.”

Necrotising soft tissue infections (NSTI) are bacterial infections which are characterised by rapid tissue degradation. Such infections, often caused by streptococci, while relatively uncommon, are extremely serious. In most cases they necessitate intensive care and can quickly become life-threatening.

Extensive surgery, intravenous antibiotics are often required to prevent the infection from spreading, and amputation may be required in extreme situations. Many patients also develop sepsis, which further complicates the course of the condition.

Early, correct diagnosis is crucial to save lives and avoid amputation, but this is complicated by factors such as vague symptoms including vomiting, fever and severe pain, as well as the heterogeneous group of patients. Despite recommendations for surgical evaluation in suspected NSTI, there is a considerable risk of misdiagnosis.

Currently, various laboratory tests, including white blood cell counts, are used as diagnostic tools, but suffer from low sensitivity. NSTI-specific biomarkers are therefore needed. The condition is classified into four types depending on the infecting organism.

Researchers at Karolinska Institutet, Haukeland University Hospital, Norway, and Copenhagen University Hospital, Denmark, have now been able to identify biomarkers specific to different patient groups with soft tissue infections.

Using machine learning, the researchers analysed 36 soluble factors in blood plasma from the 311 NSTI patients included in the international INFECT study. Control groups included patients with suspected NSTI and sepsis, respectively.

The analyses showed a new biomarker that accurately identifies patients with tissue necrosis.

“The new biomarker, thrombomodulin, proved to be superior to the laboratory parameters used clinically today. The analyses also identified biomarkers for patients with soft tissue infection caused by different types of bacteria, as well as patients who developed septic shock,” said first author Laura Palma Medina, researcher at the Department of Medicine, Karolinska Institutet (Huddinge).

Source: Karolinska Institutet

Journal information: Palma Medina, L.M., et al. (2021) Discriminatory plasma biomarkers predict specific clinical phenotypes of necrotizing soft-tissue infections. Journal of Clinical Investigation. doi.org/10.1172/JCI149523.

Self-inflicted Firearm Injuries Among Rural Youth Three Times Urban Rates

Photo by Annie Spratt on Unsplash
Photo by Annie Spratt on Unsplash

Emergency Department visits by youth for self-inflicted firearm injuries were three times more common in rural areas compared to urban ones, a national study has found.
The study, published in the Journal of Pediatrics found that Emergency Department (ED) visits by youth for self-harm were nearly 40 percent higher in rural areas compared to urban settings. Youth from rural areas presenting to the ED for suicidal ideation or self-harm also were more likely to need to be transferred to another hospital for care, which underscores the insufficient mental health resources in rural hospitals.

“Our study used pre-pandemic data, and we know that increased attention to youth mental health is even more pressing now everywhere, but especially in rural settings to prevent self-harm in youth,” said lead author Jennifer Hoffmann, MD, pediatric emergency medicine physician at Ann & Robert H. Lurie Children’s Hospital of Chicago and Assistant Professor of Pediatrics at Northwestern University Feinberg School of Medicine. “We need universal screening for suicidal ideation for all children and adolescents age 10 and up who present in the ED to identify youth at risk and intervene before tragedy occurs.”

The study drew on national data on suicidal ideation or self-harm in youth (ages 5-19 years) from a sample of EDs across the country, including those in general hospitals and children’s hospitals. The researchers extrapolated the results to arrive at national estimates.

Dr Hoffmann explained that a number of factors contribute to higher suicide rates and self-harm in rural youth. One of these is access to mental healthcare, which she said is a huge challenge. A lack of paediatric mental health professionals in rural areas is another factor, forcing patients to travel long distances for help. In addition, poor insurance coverage resulting from lower family income and unemployment. Small towns also have anonymity concerns, possibly delaying seeking care until a crisis brings the child to the ED. Firearm ownership is higher in rural firearms, so increased access to firearms may account for the high degree of disparity in self-inflicted firearm injuries.

“We need to improve mental health training for ED providers, allocate more resources and implement policies in rural hospitals on managing young patients who present with suicidal ideation or self-harm,” said Dr Hoffmann. “More widespread use of tele-psychiatry also might help prevent unnecessary transfers to other hospitals. But even more importantly, we need to train primary care providers to help diagnose and treat mental health issues earlier, so we can prevent self-inflicted injuries and death.”

Source: Ann & Robert H. Lurie Children’s Hospital of Chicago

A New Snake Venom ‘Super Glue’ For Wound Closures

Photo by David Clode on Unsplash
Photo by David Clode on Unsplash

A novel snake venom ‘super glue’ has been developed, that can stop life-threatening bleeding in under a minute.

Over the past 20 years, bioengineer Kibret Mequanint, a professor at the University, has developed an array of biomaterials-based medical devices and therapeutic technologies – some of which are either now licensed to medical companies or are in the advanced stage of preclinical testing.

This latest work focuses on a blood clotting enzyme called reptilase or batroxobin, which is found in the venom of lancehead snakes (Bothrops atrox), which are amongst the most venomous snakes in South America.

Prof Mequanint and the international research team designed a body tissue adhesive that takes advantage of the clotting property of this enzyme, incorporating it into a modified gelatin that can be packaged into a small, handy tube for easy application.

“During trauma, injury and emergency bleeding, this ‘super glue’ can be applied by simply squeezing the tube and shining a visible light, such as a laser pointer, over it for a few seconds. Even a smartphone flashlight will do the job,” said Prof Mequanint.

Compared to the industry gold standard for clinical and field surgeons, clinical fibrin glue, the new tissue sealant has 10 times the adhesive strength to resist detachment or washout from bleeding. The blood clotting time is also much shorter, halving the 90 seconds for fibrin glue to 45 seconds for this new adhesive.

This novel biotechnology could reduce blood loss and save more lives. Tests were performed in models of major bleeding, such as deep skin cuts, ruptured aortae, and severely injured livers.

“We envision that this tissue ‘super glue’ will be used in saving lives on the battlefield, or other accidental traumas like car crashes,” said Prof Mequanint. “The applicator easily fits in first aid kits too.”

Besides its trauma application, the new snake venom ‘super glue’ can be used in surgical wound closures.

The study was published in the journal Science Advances..

“The next phase of study which is underway is to translate the tissue ‘super glue’ discovery to the clinic,” said Prof Mequanint.

Source: University of Western Ontario

Journal information: Guo, Y., et al. (2021) Snake extract–laden hemostatic bioadhesive gel cross-linked by visible light. Science Advances.doi.org/10.1126/sciadv.abf9635.

Trauma Patients with COVID at Great Risk

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The COVID pandemic has placed a great strain on healthcare resources, with a number of indirect impacts ranging from increased incidence of heart attacks to decreased cancer screenings, but also increased the risk of complications and death among trauma patients with COVID. 

The study revealed that the risk of death for COVID-positive patients in trauma centres across the US state of Pennsylvania was six times higher than non-COVID-negative patients with similar injuries. Complication risk in COVID-positive patients was doubled for venous thromboembolism, renal failure, need for intubation, and unplanned ICU admission, and was five times greater for pulmonary complications. In patients over age 65, the risks were even higher. The findings were recently published in The Journal of Trauma and Acute Surgery.  

“COVID had the largest impact on patients whose injuries were relatively minor, and who we would have otherwise expected to do well,” said lead author Elinore Kaufman, MD, MSHP, an assistant professor in the Division of Trauma, Surgical Critical Care and Emergency Surgery at Penn Medicine. “Our findings underscore how important it is for hospitals to consistently test admitted patients, so that providers can be aware of this additional risk and treat patients with extra care and vigilance.”

Researchers conducted a retrospective study of 15 550 patients admitted to Pennsylvania trauma centers from March 21, 2020, (when non-essential businesses statewide were ordered close) to July 31, 2020. Of the 15 550 patients, 8170 were tested for the virus, and 219 tested positive. During this period, the researchers evaluated length of stay, complications, and overall outcomes for patients who tested positive for COVID, compared to patients who did not have the virus. They found that rates of testing increased over time, from 34% in April 2020 to 56% in July. Centres had a great variability in testing, a median of 56.2% of the time with a range of 0 to 96.4%.

“First, we need to investigate how to best care for these high-risk patients, and establish standard protocols to minimise risks,” said senior author Niels D Martin, MD, chief of Surgical Critical Care and an associate professor in the division of Trauma, Surgical Critical Care and Emergency Surgery. “Second, we need more data on the risks associated with patients who present symptoms of COVID, versus those who are asymptomatic, so we can administer proven treatments appropriately and increase the likelihood of survival with minimal complications.”

Source: University of Pennsylvania

Treating Brain Injuries with Sex-specific Interventions

New research has identified a sex-specific window of opportunity to treat traumatic brain injuries (TBIs), which scientists are exploiting in a project to create a sex-targeted drug delivery for TBI.

The study, a collaboration of The University of Texas Health Science Center at Houston (UTHealth) and Arizona State University will be used to help design nanoparticle delivery systems targeting both sexes for treatment of TBI.

“Under normal circumstances, most drugs, even when encapsulated within nanoparticles, do not reach the brain at an effective concentration due to the presence of the blood-brain barrier. However, after a TBI this barrier is compromised, allowing us a window of opportunity to deliver those drugs to the brain where they can have a better chance of exerting a therapeutic effect,” said Rachael Sirianni, PhD, associate professor of neurosurgery at McGovern Medical School at UTHealth. Dr Sirianni’s collaborator and co-lead investigator on this grant, Sarah Stabenfeldt, PhD, was the first to demonstrate that the window of opportunity created in the blood-brain barrier differed between men and women, and it was this key finding that led them to apply for funding.

TBI results from blows to the head, and in the most severe form of TBI, the entirety of the brain is affected by a diffuse type of injury and swelling. The body responds with an acute response to the injury, followed by a chronic phase as it tries to heal.

“In this second phase, a variety of abnormal processes create additional injury that go well beyond the original physical damage to the brain,” Dr Sirianni said.

Normally, the blood vessels maintain a very carefully controlled blood-brain barrier to prevent the entry of harmful substances. However, during this second phase of healing following a TBI, those blood vessels are compromised, possibly allowing substances to seep in.

One of the numerous differences between female and male patients is varying levels and cycles of sex hormones such as oestrogen, progesterone, and testosterone. While these levels already differ in healthy people, additional hormone disruption for both sexes can result from a brain injury.

Dr Sirianni explained that this work is extremely important as presently TBIs have no effective treatment options. Current treatments for TBI vary widely based on injury severity and range from daily cognitive therapy sessions to radical surgery such as bilateral decompressive craniectomies. 

“The goal of this research is to develop different nanoparticle delivery systems that can target the unique physiological state of males versus females following a TBI. Through this research, we hope to develop an optimum distribution system for these drugs to be delivered to the brain and can hopefully find an effective treatment plan for TBIs,” Sirianni said.

Drugs that previously perceived as unsafe or ineffective when given systemically can instead be targeted directly to the injury microenvironment through nanoparticle delivery systems.

“With these nanoparticle systems, we’re looking at how we can revisit a drug that showed promise in preclinical studies or clinical trials but then failed,” Stabenfeldt said.

Source: The University of Texas Health Science Center at Houston

White Matter Changes Uncovered in Repeated Brain Injury

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A new study has uncovered insights into white matter changes that occur during chronic traumatic encephalopathy (CTE), a progressive brain disease associated with repetitive head impacts. This discovery may help in identifying new targets for therapies.

CTE been diagnosed after death in the brains of American football players and other contact sport athletes as well as members of the armed services. The disease has been identified as causing impulsivity, explosivity, depression, memory impairment and executive dysfunction.

Though much prior research focused on repetitive head trauma leading to the development of abnormal tau, this study focused on white matter changes, particularly the oligodendrocytes which myelinate nerve sheaths. The results have been published online [PDF] in the journal Acta Neuropathologica.

“Research to date has focused on the deposition of abnormal tau in the gray matter in CTE. This study shows that the white matter undergoes important alterations as well.  There is loss of oligodendrocytes and alteration of oligodendrocyte subtypes in CTE that might provide new targets for prevention and therapies,” explained corresponding author Ann McKee, MD, chief of neuropathology at VA Boston Healthcare, director of the BU CTE Center.

Dr McKee and her team isolated cellular nuclei from the postmortem dorsolateral frontal white matter in eight cases of CTE and eight matched controls. They conducted single-nucleus RNA-seq (snRNA-seq) with these nuclei, revealing transcriptomic, cell-type-specific differences between the CTE and control cases. In doing so, they discovered that the white matter in CTE had fewer oligodendrocytes and the oligodendroglial subtypes were altered compared to control tissue.

Since previous studies have largely focused on the CTE-specific tau lesion located in the cortex in the brain, these findings are particularly informative as they explain a number of features of the disease. “In comparison, the cellular death process occurring in white matter oligodendrocytes in CTE appears to be separate from the accumulation of hyperphosphorylated tau,” she said. “We know that the behavioural and mood changes that occur in CTE are not explained by tau deposition. This study suggests that white matter alterations are also important features of the disease, and future studies will determine whether these white matter changes play a role in the production of behavioral or mood symptoms in CTE, such as explosivity, violence, impulsivity, and depression.”

Source: Boston University School of Medicine

Journal information: Chancellor, K. B., et al. (2021) Altered oligodendroglia and astroglia in chronic traumatic Encephalopathy. Acta Neuropathologica. doi.org/10.1007/s00401-021-02322-2.