New research examines what happens at the neuronal level during a concussion and reveals how a blow to the head causes swellings along the axon of the neuron. The new insights could help researchers to improve symptoms in patients with concussions.
When a person’s brain is exposed to sudden trauma – such as when it suddenly hits a hard surface or when an object pierces through the skull – they are said to have experienced traumatic brain injury (TBI).
TBI accounted for 2.5 million visits to the emergency department and 56,000 deaths in 2013, according to the Centers for Disease Control and Prevention (CDC).
TBI can be mild, moderate, or severe, depending on the severity of the symptoms. A person who experiences mild TBI, also called a concussion, may or may not lose consciousness for a few seconds.
According to the National Institutes of Health (NIH), additional symptoms of mild TBI are wide ranging, and include “headache, confusion, lightheadedness, dizziness, blurred vision or tired eyes, ringing in the ears, bad taste in the mouth, fatigue, or lethargy.” Symptoms can also include behavioral, mood, and sleep changes. Finally, mild TBI can also affect memory, concentration, and reasoning.
Behind these overt symptoms lie neurological mechanisms that have been explored by the medical research community to varying degrees. New research published in The Journal of Cell Biology examines a neurological aspect of concussions that, so far, had not been fully understood: the swelling of axons, a key part of neurons.
The study was carried out by a team of scientists from the Ohio State University in Columbus, and the first author of the study was Chen Gu.
Gu and colleagues examined how “varicosities” form along neurons’ axons during concussion. An axon is one of the three components of a neuron, along with dendrites and the cell body. The axon sends electrical signals from the cell body to other neurons.
Gu and colleagues found that they could induce these swellings in the neurons of the hippocampus, which is the brain region responsible for creating and storing new memories.
Researchers injected the axons with bursts of liquid from a small pipette, creating a pressure similar to the one that the neurons may experience following a blow to the head.
These swellings – namely, concussion-typical varicosities – formed very quickly, and especially rapidly in young neurons, where they formed within 5 seconds.
What was surprising was that the swellings disappeared after a few minutes. This suggests that axonal varicosities do not indicate irreversible degeneration of the axons.
Gu and team also repeatedly induced axonal varicosities in cultured neurons, imitating the effects of repetitive blows to the head. They compared these swellings with the ones they induced in mice.
The researchers discovered that this method of injecting liquid into the axons, or “puffing” them, activates a protein called TRPV4, which is a channel protein found more abundantly in the membrane of neuronal axons. It enables calcium ions to permeate the cell.
Gu and team managed to inhibit this channel and consequently block the formation of additional swellings along the axons.
Furthermore, the researchers were able to identify more precisely the mechanism responsible for swelling formation.
Specifically, they could see that after calcium ions enter the cell via the activated TRPV4 channels, they inhibit another protein called STOP, which, in turn, disrupts the transport of cellular materials along the axons. These materials then accumulate along the axon, causing varicosities.
The researchers also noticed that older neurons have lower amounts of TRPV4 and higher levels of STOP. Older neurons are more resilient to the effects of induced puffing.
“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.
The first author of the study also comments on the overall significance of the findings, saying, “Taken together, our findings provide novel mechanistic insights into the initial stage of a new type of neuronal plasticity in health and disease.” He concludes:
“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.”