Researchers investigate novel approach to regenerating the brain after a stroke

Four-and-a-half hours; this is the critical window of time for stroke victims to be eligible for treatment at the hospital after a stroke begins to affect the brain.

Within this tight window, a patient must have an official stroke diagnosis at the hospital and be ready to receive the only FDA-approved treatment of its kind to re-establish flow to blood vessels affected by stroke.

"When a stroke occurs, it's essential to reach the hospital as quickly as possible, as the closer the treatment is to the time of the event, the better the chances of a positive outcome," said Lina Nih, assistant professor in UNLV's Department of Brain Health, housed within the School of Integrated Health Sciences. "The timing is crucial, as it helps determine whether the person is a candidate for treatment."

According to Nih, who recently joined UNLV's School of Integrated Health Sciences from UCLA's David Geffen School of Medicine, 96% of patients arrive at the hospital too late to receive the treatment.

Nih has spent more than a decade developing treatments that could potentially be injected directly into the stroke lesion to regenerate the dead brain tissue lost after a stroke. Her promising findings using rodent models have been shown to regenerate nearly 70% of the vascular and neuronal tissue lost from the initial stroke.

While receiving or missing medical care within this ephemeral therapeutic window can make or break a stroke patient's ability to regain mobility, Nih is hopeful that her novel treatments can make it so time doesn't necessarily have to be of the essence.

How the brain reacts after a stroke

"It's important to remember that blood vessels bring oxygen and glucose to all organs in the body. If that blood flow is interrupted, then the flow of glucose and oxygen is also interrupted," Nih said.

"The vast majority of organs have a storage system of oxygen and glucose that can last a few minutes, hours, or sometimes days. The brain, however, is a different story."

According to Nih, brain cells begin to suffer within a minute after the initial interruption of blood flow. And after about 90 seconds, the affected cells begin to die, after which they implode and release their internal content in the brain tissue. This can be extremely toxic to the neighboring cells and can perpetuate cell death in the healthy adjacent tissue.

Despite this potentially cataclysmic sequence of events, Nih is confident that the brain is capable of regenerating cells previously lost during stroke.

"The answer is complex, but the simple answer is that the brain has a dormant capacity for regenerating its lost and damaged cells," she said.

According to Nih, this capacity comes from when our brain and spinal cords were developed as an embryo. "There are ways now with innovative technologies to awaken these repair mechanisms to regenerate the tissue that was lost after injury," she said.

The secret to regenerating blood vessels

The conversation on how brains can regenerate lost and/or damaged cells dates back decades, but Nih's approach lies within the blood vessels, as opposed to the neurons—which is the favored approach currently for a majority of the medical and scientific community.

"I am convinced that it is the brain's own blood vessels that awaken and control these repair mechanisms that then regenerate the lost cells," she added.

And her work over the past decade has been focused on proving these theories right.

"Blood vessels change size and shape over time," she said. "It's fascinating to watch blood vessels around the lesion site grow and remodel weeks after a stroke. I've spent the last decade observing vessels following a brain injury day after day, week after week, to watch this dance from afar and understand what they're trying to say."

Developing life-saving stroke treatments

To complement her unique approach to studying brain vessels after a stroke, Nih has also been diligently working on a possible treatment. Injected directly into the brain following a stroke, the treatment would, ideally, awaken brain vessels and kick-start the mechanisms needed to regenerate the lost tissue.

"We are capable of creating artificial brain tissue that is fully liquid at room temperature, which can then be loaded into a syringe and injected directly into the area of lesion in the brain. Once in the brain, it can solidify into a jello-like material," she said.

After the gel is injected, it communicates with the brain's vessels to grow specific sections of the brain and activate their mechanisms of repair to regrow the previously dead tissue.

Nih likened this experiment to a grand orchestra, each instrument representing a part of the brain's intricate systems. Together, they strive to master the art of improvisation, harmonizing unpredictable interactions to uncover a melody—the elusive key to regeneration—that has yet to be composed.

For those who prefer nature over music, the process is akin to the growth of new trees in the forest.

"You will never see a branch growing outside of a tree. If you want a new branch, you look for a tree that is already there. It's the same with vessels. You can only grow them out of pre-existing vessels. They grow and divide," she said.

"When you look at them over time, you can see them change shape, density, etc. They start growing around the lesion site, and then eventually inside the lesion site. Once inside, they start reconnecting brain circuits. This can then recreate the functions that were lost. Without blood vessels, the neurons would never grow."

Nih's next steps are to continue developing more efficient translational treatments for stroke, with the ultimate goal of establishing a biotech startup and initiating clinical trials within the next few years. If those results are encouraging, she hopes that the four-and-a-half-hour window might not be the fait accompli for the outcome of stroke patients.

"Patients who recover well have way more blood vessels around their brain lesions than those who don't. What or who made these vessels grow?" she asked. "That's what I hope to find out."

Provided by University of Nevada, Las Vegas