Tag: traumatic brain injury

Brain Glue Heals Neural Damage from Brain Injuries

In a new study, researchers at the University of Georgia’s (UGA) Regenerative Biosciences Center have shown that the “brain glue” they developed protects against loss of brain tissue after a severe injury, and may also help in functional neural repair.

Significant traumatic brain injury (TBI) commonly results in extensive tissue loss and long-term disability, with no clinical treatments available to prevent this.

The new finding is the first to provide visual and functional evidence of the repair of brain neural circuits involved in reach-to-grasp movement in brain glue-implanted animals following severe TBI.

“Our work provides a holistic view of what’s going on in the recovery of the damaged region while the animal is accomplishing a specific reach-and-grasp task,” said lead investigator Lohitash Karumbaiah, an associate professor in the University of Georgia’s College of Agricultural and Environmental Sciences.

The brain glue developed by Prof Karumbaiah was designed to mimic the meshwork of sugars supporting brain cells. The hydrogel contains key structures that bind to two protective protein factors that can enhance the survival and regrowth of brain cells after severe TBI: basic fibroblast growth factor and brain-derived neurotrophic factor.

In previous research, Prof Karumbaiah and his team demonstrated that the brain glue conferred significant protection to brain tissue from severe TBI damage. In order to tap the neuroprotective capability of the original, they changed the delivery surface of protective factors to help accelerate the regeneration and functional activity of brain cells.

“Animal subjects that were implanted with the brain glue actually showed repair of severely damaged tissue of the brain,” said Karumbaiah. “The animals also elicited a quicker recovery time compared to subjects without these materials.”

The team used a tissue-cleaning method to make the brain less opaque, allowing them to 3-D image the cells’ response in the reach-to-grasp circuit, which is similar in rats and humans.

“Because of the tissue-clearing method, we were able to obtain a deeper view of the complex circuitry and recovery supported by brain glue,” said Prof Karumbaiah. “Using these methods along with conventional electrophysiological recordings, we were able to validate that brain glue supported the regeneration of functional neurons in the lesion cavity.”

“Doing the behavioral studies, the animal work and the molecular work sometimes takes a village,” said Karumbaiah. “This research involved a whole cross-section of RBC undergraduate and graduate students, as well as faculty members from both UGA and Duke University.”

Source: Medical Xpress

Journal information: Charles-Francois V. Latchoumane et al. Engineered glycomaterial implants orchestrate large-scale functional repair of brain tissue chronically after severe traumatic brain injury, Science Advances (2021). DOI: 10.1126/sciadv.abe0207

New Test Picks up Concussion Biomarkers in Saliva

A new test has been found to effectively pick up concussion biomarkers in the saliva of rugby players.

This paves the way for a non-invasive, easy-to-use pitch-side test to rapidly detect concussions for early treatment. Concussion is a serious problem in contact sports, with players such as college American Football athletes consistently underestimating its risk. Missing a concussion can have a range of consequences, from delayed recovery to more serious (albeit rare) injuries such as traumatic brain swelling.

Detecting concussions requires an assessment by a clinician of the signs and symptoms of the injury. However, recent advances in DNA sequencing technology have made it possible to use small non-coding RNAs (sncRNAs) as biomarkers in rapid tests. sncRNAs regulate the expression of different cellular proteins associated with various diseases, such as cancer and Alzheimer’s disease.

t is thought that since saliva can receive cellular signals directly from the cranial nerves in the mouth and throat, biomarkers from a brain injury would quickly show up.

A panel of 14 sncRNAs differentiated concussed players from those where traumatic brain injury had been suspected but ruled out, and from the comparison group, both straight after the game and 36–48 hours later.

Over two seasons, samples were collected before the rugby season began from 1028 players from the two elite professional tiers, and during standardised ‘gold standard’ head injury assessments at three time points—during the game, afterwards, and 36–48 hours later from 156 of these players .

The researchers also took saliva samples from a comparison group of 102 uninjured players, as well as 66 with muscle or joint injuries, and so had not had head injury assessments.

However, the researchers stressed that the observational study nature and design of this study cannot show that the biomarker test is any better than a gold standard clinical test for concussion.

“In community sport, [sncRNAs] may provide a non-invasive diagnostic test that is comparable in accuracy to the level of assessment available in a professional sport setting,” while the test could be added to current head injury evaluation protocols at the elite level,” they add.

And as the biology of concussion is still not fully understood, sncRNAs might help to shed light on the response to injury as this evolves over time, they suggest.

“The detection of signatures of concussion at early time points in saliva (a non-invasively sampled biofluid) presents both at the pitch side, and in primary care and emergency medicine departments, an opportunity to develop a new and objective diagnostic tool for this common clinical presentation,” they conclude.

As an addendum to their findings, they added: “A patented salivary concussion test is in the process of being commercialized as an over-the-counter test for elite male athletes.

“Meanwhile our research team aims to collect further samples from players in two elite men’s rugby competitions to provide additional data to expand the test and develop its use. This will guide the prognosis and safe return to play after concussion and further establish how the test will work alongside the head injury assessment process.”

The researchers plan to add more participants to the SCRUM study, such as female athletes and community players.
Source: Medical Xpress

Journal information: Valentina Di Pietro et al. Unique diagnostic signatures of concussion in the saliva of male athletes: the Study of Concussion in Rugby Union through MicroRNAs (SCRUM), British Journal of Sports Medicine (2021). DOI: 10.1136/bjsports-2020-103274

Plasma microRNAs as Biomarkers for Mild Brain Injury

Plasma microRNA could serve as biomarkers for the detection and diagnosis of mild traumatic brain injury, a recent study from the University of Eastern Finland (UEF) has found.

Mild traumatic brain injury is extremely difficult to detect as it is almost invisible to most imaging techniques, and visible signs in daily life may be masked by compensation for increased task difficulty.

Blood biomarkers can satisfy the demand for timely, accurate, easily accessible and affordable tests for mild traumatic brain injury. They are minimally invasive and can provide molecular information about the injury on an ongoing basis.

MicroRNAs (miRNAs) are non-coding sections of RNA that play a key role in gene expression. The researchers sequenced DNA in blood plasma taken from animal models subjected to mild and severe traumatic brain injury. They selected the miRNAs which showed the greatest potential for use as biomarkers for further analysis with polymerase chain reaction (PCR). They wanted biomarkers that were both sensitive and specific to traumatic brain injury in an animal model.

Dr Noora Puhakka, A. Virtanen Institute for Molecular Sciences, UEF, said, “We have been developing a suitable analysis and measurement method especially for miRNAs that can be found in small amounts in plasma, and this method is based on digital droplet PCR.

“Humans and animals share many identical miRNAs, and this makes them excellent candidates for translational studies, where results achieved in animal models are sought to be applied in humans. However, it has proven challenging to reproduce results from different studies and different sets of data. This is why assessing the quality of measurement methods, and reproducibility, is an extremely important part of biomarker research.”
The study a pair of possible biomarker candidates to diagnose mild traumatic brain injury both in the animal model and in human patients.  

“We found two interesting biomarkers in the animal model, the plasma miRNAs miR-9a-3p and miR-136-3p, which we then decided to analyse in blood samples taken from patients with traumatic brain injury. Elevated levels of these biomarkers allowed us to identify some of the patients who had experienced a mild traumatic brain injury,” Dr Puhakka explained.

“Both of these miRNAs are more abundant in the brain than in other tissues, and their elevated levels in plasma could possibly be due to brain injury and the level of its seriousness. However, further research in larger patient cohorts is still needed.”

Source: News-Medical.Net

Journal information: Gupta, S. D., et al. (2021) Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury. International Journal of Molecular Sciences. doi.org/10.3390/ijms22041563.

Young Athletes’ Recovery Helped by New Concussion Guidelines

A study has found that the adoption of new concussion guidelines, which emphasises a more active form of rest, reduced the duration of symptoms among athletes aged 11 to 18.

Concussions are the most common form of traumatic brain injury, often occurring either as a direct result of a blow to the head, or from forces experienced by the body that impart an acceleration to the head. Symptoms include mood changes, cognitive changes, sensory phenomena such as headaches or dizziness, and changes in sleep pattern.

The researchers compared medical records from 2016-18, which used the newer guidelines, to a set from 2011-13, which used the older guidelines.

Lead researcher John Neidecker, DO, and Sports Concussion Specialist, explained: “The most significant change in care involved a shift from strict rest or cocoon therapy to a return to low-intensity physical or cognitive activity after 24 to 48 hours. Our results show active rest dramatically improved recovery times among young athletes with first-time concussions.”

Active rest involves light activity that steadily increases under supervision, with minimal head movement.

“If diagnosis of a pre-existing condition has never been given, patients cannot be expected to report one during our concussion assessment,” said Dr. Neidecker. “This is especially true in the adolescent age group, as some may have a condition that they are not aware of yet. This makes screening for preexisting conditions more complex, yet even more essential for this age group.”

For example, intolerance to 3D movies could indicate an unrelated pre-existing condition. Information from parents about preinjury personality and behaviour could uncover anxiety.

“This more individualised, osteopathic approach in screening the athletes’ past medical history helped us identify health issues that may have been overlooked in the past,” said Dr Neidecker. This allows treatment to be more effectively tailored, he explained.

Knowledge about concussions has improved; in the 2011-13 dataset, the counselling given was more cautious and ominous, Dr Neidecker noted. Adequate communication and a positive outlook may have helped reduce reported symptoms, and may be essential for patients with anxiety. 

Source: News-Medical.Net


Journal information:
 Neidecker, J. M., et al. (2021) First-time sports-related concussion recovery revisited: management changes and impact on recovery. Journal of Osteopathic Medicine. doi.org/10.1515/jom-2020-0106.