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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.”
By David Stirt
(Editor’s Note: What follows is an excerpt from an article that appears in February issue of Concussion Litigation Reporter)
Data released by the National Football League on Jan. 26, 2017 revealed that while there were fewer players sustaining concussions during the 2016 season (244) versus the 2015 season (271), the 2016 numbers were in line with the five-year average (242) of concussions per season. While the total number of concussions reported in 2016 is lower than the 2015 total, it is higher than the numbers reported in both 2013 (229) and 2014 (206).
“It’s certainly positive that concussions were down this year across categories, but I think putting too much focus on any one year would be mistaken,” said Jeff Miller, the NFL’s executive vice president of health and safety policy. “The goal here is to drive those numbers down through rules changes, culture changes, protocol changes, through greater observation and treatment over a longer term period of time.”
Dr. Robert Heyer, president of the NFL’s Physician’s Society and team internist for the Carolina Panthers pointed out a cultural change within the NFL that may explain, in part, why … (To subscribe, visit https://concussionpolicyandthelaw.com/subscribe/)
U.S. Secretary of Veterans Affairs Robert A. McDonald, Olympic Gold Medalist Nancy Hogshead-Makar, and Super Bowl Champion Phil Villapiano pledge brains to Concussion Legacy Foundation
Secretary of Veterans Affairs (VA) Robert A. McDonald, three-time Olympic gold medalist swimmer Nancy Hogshead-Makar, and former Oakland Raiders linebacker and Super Bowl champion Phil Villapiano pledged earlier this week to donate their brains to the Concussion Legacy Foundation, which collaborates with the VA and Boston University as part of the VA-BU-CLF Brain Bank.
The announcements of Villapiano and Hogshead-Makar were planned as part of the VA-hosted Brain Trust: Pathways to InnoVAtion, a public-private partner event which brought together many of the most influential voices in the field of brain health to identify and advance solutions for mild traumatic brain injury (mTBI) and Post Traumatic Stress Disorder (PTSD). Secretary McDonald’s announcement was not planned for the event.
“As I listened to the very powerful personal stories from Veterans and the challenges the world’s top researchers are working to overcome in TBI, I made a decision: I decided to join the hundreds of Veterans and athletes who have already donated their brain to the VA Brain Bank so that I may, in a small way, contribute to the vital research happening to better understand brain trauma,” said Secretary McDonald. “This is a very, very serious issue, one that affects Veterans and non-Veterans alike. I’m proud to do my part because I know that the researchers at VA are committed to improving lives and they have my full support.”
The pledges were made as part of the Foundation’s My Legacy campaign, which encourages athletes to leave their legacy by helping solve the concussion crisis through brain donation or other means. Villapiano pledged in honor of his former teammate, Hall of Famer Ken Stabler, who died in 2015 and was diagnosed with CTE at the VA-BU-CLF Brain Bank. He joins former Oakland Raiders teammates George Atkinson, Art Thoms, and George Buehler, who pledged last month.
“I’d go back and smash my head into anybody, any time. I loved that kind of stuff. Little did I know what has happening inside our heads,” Villapiano said. “Chronic traumatic encephalopathy is a big problem and all of my friends are scared to death.”