March 19, 2020
Investigators used a novel approach to prevent the swelling that can occur after traumatic brain injury (TBI) in a mouse model: they injected nanoparticles that trick white blood cells into going after them instead of rushing to the injured brain and causing an inflammatory and immune response.
Mice with TBI that were given three injections of the immunomodulatory nanoparticles beginning two to three hours after injury showed less brain swelling and damage on MRI as compared with mice with TBI that did not get the nanoparticles; the treated mice also performed better on functional tests.
The immunomodulatory nanoparticle treatment, if further proven in preclinical trials and human trials, would not undo damage from the initial injury to the brain. But it could help prevent the body from setting off a cascade of immune and inflammatory cells in reaction to the injury, which in turn can cause brain swelling and even more damage to brain tissue.
“We certainly haven’t gone and magically prevented that initial damage,” said Jack Kessler, MD, professor of neurology at Northwestern University Feinberg School of Medicine and the senior author of the paper. “What we can do is prevent the secondary damage, which is substantial.”
Predicting which TBI patients will develop edema of the brain isn’t easy, so having a preventive treatment like the nanoparticles that could be administered upfront could be life-altering, Dr. Kessler said.
He said some patients with head injuries “come into the hospital walking and talking, but then their brain swells, and they die.”
According to background in the study, published January 10 online in Annals of Neurology, each year more than 2.5 million people in the US have a traumatic brain TBI and more than five million Americans live with at least one sequela of TBI.
“After the primary injury, there is substantial secondary injury attributable to infiltrating immune cells, cytokine release, reactive oxygen species, excitotoxicity, and other mechanisms,” the study authors wrote. “Despite many preclinical and clinical trials to limit such secondary damage, no successful therapies have emerged.”
More About the Nanoparticles
The nanoparticles tested in the mouse experiments are made of material used in biodegradable sutures. The paper specifically described the particles as “highly negatively charged, 500 nm-diameter particles composed of the Food and Drug Administration (FDA)-approved biodegradable biopolymer carboxylated poly (lactic-co glycolic) acid.”
The nanoparticles (IMPs), which seem like foreign invaders to the body’s immune system, attract the attention of large white blood cells known as monocytes, which have been implicated in the secondary damage that occurs with TBI.
“IMPs bind to the macrophage receptor with collagenous structure (MARCO) on monocytes and monocytes bound to IMPs no longer home to sites of inflammation but rather are sequestered in the spleen,” where the cells die, the study authors wrote.
The mouse study involved two types of head injury. In some of the mice, the researchers performed a craniotomy to create a controlled cortical impact. Other mice received a closed head injury involving a direct blow to the head. Both types of injuries were meant to mimic what occurs in humans with TBI.