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Researchers from The Ohio State University have announced they have discovered how blows to the head cause numerous small swellings along the length of neuronal axons. The study, “Polarity of varicosity initiation in central neuron mechanosensation,” which will be published June 12 in The Journal of Cell Biology, observes the swelling process in live cultured neurons and could lead to new ways of limiting the symptoms associated with concussive brain injuries.
Mild traumatic brain injuries, or concussions, cause a variety of temporary symptoms, including headache, nausea, and memory loss. But the effects of concussive impacts on neurons in the brain are poorly understood. One such effect is the development of “axonal varicosities,” small, bead-like swellings that appear along the length of neuronal axons, which are the parts of neurons that transmit electrical and chemical signals to neighboring nerve cells. Similar swellings are seen in the degenerating axons of Alzheimer’s and Parkinson’s patients.
Chen Gu and colleagues at The Ohio State University discovered that they could induce the formation of axonal varicosities in hippocampal neurons grown in the lab by “puffing” them with bursts of liquid from a small pipette. The pressure exerted by these puffs was similar to the forces neurons might experience after a blow to the head.
The axonal varicosities formed rapidly, particularly in younger neurons where they swelled up within 5 seconds of being puffed. A surprise to the researchers was that the varicosities disappeared several minutes after puffing, indicating that they are not a sign of irreversible axon degeneration.
Gu and colleagues could also induce axonal varicosities by repeatedly puffing cultured neurons with shorter bursts of liquid, mimicking the effects of repetitive, subconcussive impacts. Accordingly, the team also saw axonal varicosities in the brains of mice subjected to repeated light blows to the head.
The researchers found that puffing activated a mechanosensitive channel protein called TRPV4, which is enriched in the membrane of neuronal axons and allows calcium ions to enter the cell. Inhibiting this channel blocked the formation of axonal varicosities.
After entering axons through activated TRPV4 channels, calcium ions appear to disrupt the microtubule cytoskeleton by inhibiting a microtubule-stabilizing protein called STOP. This interrupts the transport of cellular materials along axonal microtubules, causing these materials to accumulate at several points along the axon where they may give rise to varicosities.
Older neurons, which are more resistant to the effects of puffing, express lower levels of TRPV4 and higher levels of STOP. “It will be interesting to determine whether these factors make a mature brain more resistant to mild traumatic brain injury than a young brain,” says Gu.
Puffing didn’t induce varicosities along the lengths of dendrites, the parts of neurons that receive chemical signals from neighboring nerve cells. Instead, the researchers found that dendritic, but not axonal, varicosities could be induced by prolonged treatment with glutamate, an excitatory neurotransmitter that is released from damaged axons.
“Taken together, our findings provide novel mechanistic insights into the initial stage of a new type of neuronal plasticity in health and disease,” says Gu, who points out that axonal varicosities have also been observed in healthy brains where neurons may respond to mechanical signals from their environment. “This process may therefore play a key role in neural development and central nervous system function in adults, as well as in chronic brain disorders and various acute brain injuries.”
Sport-related concussion, one of the most complex injuries in sports medicine, is the focus of a new special issue of the Journal of Athletic Training, the scientific publication of the National Athletic Trainers’ Association.
“Over the last 20 years, our understanding of concussion mechanics, injury assessment and management has increased dramatically. We’ve made great strides with regard to education, research and legislation,” says special issue Guest Editor Steven Broglio, PhD, ATC, director, Neurotrauma Research Laboratory, University of Michigan. “Having the right multidisciplinary medical team in place, including the athletic trainer, who plays an important role in injury prevention and treatment, is vital. Our universal goal is to reduce the risk of injury and ensure a gold standard of care should concussion occur.”
Concussions during sport and recreation occur as often as 3.8 million times a year,1 resulting in up to seven injuries per minute every day of the year in the United States. Although each patient requires individual management, 90 percent of concussed athletes recover by day seven after injury.2 Concussive injuries compose 8.9 percent of all high school and 5.8 percent of all college athletic injuries.3
Key points from select studies published in the issue:
- Head-impact sensors have limited applications to concussion diagnosis but may provide sideline staff with estimates of athlete exposure and real-time data to monitor players.
- Given that concussion risk is inﬂuenced by many factors in addition to impact biomechanics, viewing an athlete’s head-impact data may provide context for the clinician working on the sidelines, but impact sensors should not replace clinical judgment.
- Amnesia was the predictor that most inﬂuenced clinical recovery from concussion.
- Loss of consciousness, concussion history and acute symptom group did not substantially affect symptom, cognitive or balance outcomes.
- Most injured athletes recovered within the normal timelines established by the Graded Symptom Checklist, Standardized Assessment of Concussion and Balance Error Scoring System.
- Compared with high school athletes who had access to an athletic trainer, those without such access were less knowledgeable about concussion.
- Access to an athletic trainer was not linked to high school athletes’ concussion-reporting percentages. However, such access was related to 10 reasons for not reporting a concussion.
- The most common reasons for not reporting a concussion were not wanting to lose playing time, not thinking the injury was serious enough to require medical attention and not wanting to let the team down.
- Per 10,000 athlete-exposures, the rates of sport-related concussion were highest in football (9.21), boys’ lacrosse (6.65), and girls’ soccer (6.11).
- Among sex-comparable sports, the rate of sport-related concussion was 56 percent higher in girls than in boys.
- Most athletes with sport-related concussions returned to play after seven days, despite resolution of symptoms in a smaller proportion within one week.
“No sports medicine topic is more polarizing than concussion, and today’s standard of care supersedes where we were just a decade ago,” says Broglio. “With validated measures, more and more of the guesswork is being removed from the process. While many questions persist about more sophisticated diagnostic measures, rehabilitation and long-term effects of injury, we continue to make great progress, remain current on research and new techniques and provide the best possible care for our patients at any level of sport or activity.”
Other suggested articles in the special issue:
- “If You’re Not Measuring, You’re Guessing: The Advent of Objective Concussion Assessments”
- “A Multifactorial Approach to Sport-Related Concussion Prevention and Education: Application of the Socioecological Framework”
- “Rest and Return to Activity After Sport-Related Concussion: A Systematic Review of the Literature”
1Langlois JA, Rutland-Brown W, Wald MM. The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil. 2006;21(5):375–378.
2McCrea M, Guskiewicz KM, Randolph C, et al. Incidence, clinical course, and predictors of prolonged recovery time following sportrelated concussion in high school and college athletes. J Int Neuropsychol Soc. 2013;19(1):22–33.
3Gessel LM, Fields SK, Collins CL, Dick RW, Comstock RD. Concussions among United States high school and collegiate athletes. J Athl Train. 2007;42(4):495–503.
The Brain Injury Association of America (BIAA) has submitted written testimony to the House Appropriations Subcommittee on Labor, Health and Human Services, Education, and Related Agencies calling for increased fiscal year 2018 appropriations for Traumatic Brain Injury (TBI) Act programs, including the state grant program, and for TBI Model Systems research funded by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR).
BIAA is also working with the Congressional Brain Injury Task Force (CBITF) Co-chairs to obtain support from Congressional members for increased funding. Individuals who are attending Brain Injury Awareness Day can download a copy of the CBITF letter to give to their Representatives during their office visits that day. If you are not able to attend, click here to download a sample letter you can send to your representative.