"Science" prevents the long-term effects of traumatic brain injury

Someone suffered a car accident and suffered a head injury

This is a common situation after traumatic brain injury-many people experience bad side effects after months or years

"Science" magazine published a paper entitled Complement factor C1q mediates sleep spindle loss and epileptic spikes after mild brain injury on September 10, 2021

Dr.

In a new study published in the journal Science, Paz and her team helped close this gap

Fragile brain area

Traumatic brain injuries, from minor concussions to severe injuries, can be the result of falls, sports injuries, gunshot wounds, head hits, explosions, or domestic violence

"These injuries are common and can happen to anyone," said Paz, who is also an associate professor of neurology at the University of California, San Francisco (UCSF) and a member of the Kavli Institute for Fundamental Neuroscience

To do this, Paz and her team recorded the activity of different cells and circuits in the brains of mice after brain injury

Paz said: "From the time of injury to the next few months, we collected so much data that our computer crashed

When a head is injured, the area of ​​the brain called the cerebral cortex is usually the main part of the injury because it is located directly under the skull

But at a later point in time, the researchers found that another area-the thalamus-was even more damaged than the cortex

The lead author of the study, Dr.

The Bath Lab spoke with Ai Aronika, MD, Ph.

Paz said: "Our research answers some very big questions in this area, such as what changes have occurred in the brain after trauma, how, and which changes are actually important to cause defects

The correct way to treat chronic effects after traumatic brain injury

The C1q molecule is part of the immune pathway, and it plays a very good role in brain development and normal brain function
.
For example, it protects the central nervous system from infections and helps the brain forget memories-this is the process required to store new memories
.
The accumulation of C1q in the brain has also been studied in various neurological and psychiatric diseases, and it is related to diseases such as Alzheimer's disease and schizophrenia
.

"C1q may be good or bad," Paz said
.
"We wanted to find a way to prevent the harmful effects of this molecule without affecting its beneficial effects
.
This is an example of why neuroscience is now a very difficult field, but it also makes it a very difficult field.
Exciting
.
"

She and her team decided to use the "incubation period" after traumatic brain injury, during which changes in the brain occur, but before long-term symptoms appear
.

Paz said: "For example, my cousin was hit in the head when he was 10 years old, and the impact shattered his skull and damaged his brain
.
But he didn't develop epilepsy until he was 20 years old
.
This incubation period It provides us with an opportunity to intervene, hoping to change this disease and prevent any complications
.
"

Paz contacted her collaborators at Annexon Biosciences and they produced a clinical antibody that can block the activity of the C1q molecule
.
Then, her team used the antibody to treat mice with brain damage to see if it might have a beneficial effect
.

When the researchers studied mice that were genetically engineered to lack C1q during trauma, the brain damage appeared to be more severe
.
However, when they selectively blocked C1q with antibodies during the incubation period, they prevented chronic inflammation and loss of thalamic neurons
.

Holden said: "This shows that the C1q molecule should not be blocked when injured, because at this stage, it may be very important to protect the brain and help prevent cell death
.
But at a later point in time, blocking C1q can actually reduce the harmful effects.
Inflammation
.
This is a way to tell the brain, “It’s okay, you have completed the protective part, and now you can eliminate inflammation
.
”

"For patients suffering from acute brain injury, there is currently a lack of treatment," said Dr.
Ted Yednock, Executive Vice President and Chief Scientific Officer of Annexon Biosciences, who is also one of the authors of the study
.
"This result is exciting because it shows that we can treat patients within hours to days after acute trauma such as traumatic brain injury to prevent secondary neuronal damage and provide significant functions.
Benefits
.
"

Potential treatment pathway

In addition to chronic inflammation, Paz and her team also found abnormal brain activity in mice with traumatic brain injury
.

First, the researchers noticed the interruption of the sleep spindle, which is the normal brain rhythm that occurs during sleep
.
These are very important to consolidate memory
.
Scientists also found the peak of epilepsy, that is, abnormal fluctuations in brain activity
.
These peaks may disrupt cognition and normal behavior, and also indicate that seizures are more likely to occur
.

Scientists have observed that anti-C1q antibody treatment not only helps restore sleep spindles, but also prevents the development of epileptic activity
.

Holden said: "In general, our research shows that targeting C1q molecules after injury can avoid some of the most destructive, long-term consequences of traumatic brain injury
.
We hope this will ultimately promote the development of traumatic brain injury treatments.

.
"

Annexon’s anti-C1q inhibitors are designed to treat a variety of autoimmune and neurological diseases, and have been tested in clinical trials, including for an autoimmune disease called Guillain-Barré syndrome.
The drug has been proven Human beings are safe
.

Yednock said: "In fact, this drug is already in clinical trials, which may speed up the speed at which patients can finally get treatment
.
We have learned about safe and effective drug dosages that can block C1q in patients' brains and can directly enter the study.
To improve the chronic effects of traumatic brain injury
.
"

Holden has previously worked with people who have experienced brain injuries and heard many of their personal stories.
For him, the impact of this research is particularly meaningful
.

"For many people I meet, brain injury is a hidden disability," she said
.
"The side effects they experience are difficult to diagnose, and their doctors usually cannot provide any medical treatment
.
It is very encouraging to be able to help find ways to treat the harmful consequences of an injury
.
"

Paz and her laboratory are continuing to expand their understanding of what happens to the brain after the injury
.
Next, they will focus on studying whether they can help prevent seizures, a symptom frequently reported by patients with severe brain injury
.

She added: “Our goal is to find a treatment that can provide treatment to patients who have suffered trauma and prevent chronic inflammation in the brain, sleep disruption, and seizures
.
If our research can help achieve this, it’s not very Okay?"

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Science

DOI 10.
1126/science.
abj2685