People with traumatic brain injuries (TBIs) can develop long-lasting secondary disorders after the initial blow. A research team at the New Jersey Institute of Technology (NJIT) is hoping to stop the process with a self-assembling peptide hydrogel.
When injected directly to the brains of rats with TBIs, the hydrogel helped blood vessels regrow and improved neuronal survival, NJIT scientists Biplab Sarkar and Vivek Kumar announced at the recent American Chemical Society meeting in San Diego.
After TBIs, the brain can accumulate glutamate, which kills some neurons in what’s called glutamate-dependent neurotoxicity, the researchers explained at a press briefing. This situation can be marked by overreactive oxygen-containing molecules (known as oxidative stress), inflammation and disruption of the blood-brain barrier. Moreover, TBI survivors can experience impaired motor control and depression.
“We wanted to be able to regrow new blood vessels in the area to restore oxygen exchange, which is reduced in patients with a TBI,” Sarkar said in a statement. “Also, we wanted to create an environment where neurons can be supported and even thrive.”
Sarkar and Kumar had previously developed peptides that can self-assemble into hydrogels when injected into rats. The platform allows for the regeneration of a variety of brain functions by carrying different snippets of amino acid sequences. Previously, they used the technology to grow new blood vessels in mice.
In this case, they used sequences that closely resemble what's found in brain tissue. They also attached a sequence from a neuroprotective protein called ependymin.
A week after injecting the gel in rats, the team examined their brains and noticed that the treated rodents had about twice as many neurons at the injury site than the control animals did. “These nanofibers form these gel-like structure,” Sarkar explained at the conference. “They can help cortical neurons from rats to hold onto these nanofibers and survive longer term.” Signs of new blood vessel formation were also observed.
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In 2014, TBIs resulted in about 2.53 million emergency department visits in the U.S., according to the Centers for Disease Control and Prevention.
Scientists are developing new ways to contain the damage. A team at the University of California, San Francisco and the University of Washington recently designed an artificial protein called LOCKR that could modulate the immune response in TBIs and keep inflammation in check. Researchers at UT Southwestern previously found that tamping down the LZK gene might help the brain and spinal cord recover from injury.
The NJIT researchers noted that they needed to inject the hydrogel directly in a rat’s brain just seconds after a TBI, which is not ideal, because it would be impossible to give a patient the treatment within that short period of time.
“Ideally, you’d like a pop-up pill or at least do an IV,” Sarkar said. “We’re trying to solve that problem: How do we inject this material in the bloodstream and pass the blood-brain barrier … to actually supply the material in the injury site?”
Though the researchers also found signs that the treated rats exhibited more improved movement abilities than those in the control group did, they want to study the animals further so they can confirm behavioral progress, Sarkar said.
Next up, the team wants to explore combining their previous blood vessel-growing peptide and the new version to see whether it could enhance recovery. And the researchers plan to examine whether the hydrogels work for more diffuse brain injuries such as concussions.