Drug shown to aid injured adult brains may exacerbate cognitive problems in children

January 10, 2017 by Lauren Ingeno
Credit: Drexel University

Traumatic brain injury (TBI) is one of the leading causes of disability and death in infants and children in the United States, with more than half a million affected annually, according to the Centers for Disease Control and Prevention. Those under age 4 who experience brain trauma can suffer lifelong problems with memory, attention and other executive functions.

While there are no drugs available to treat these injuries, scientists have shown that certain antibiotics—which inhibit the 's inflammatory response—can improve outcomes for adult animal models that have suffered a blow to the head.

However, this treatment seems to negatively affect brains that have not yet developed, according to a new study from Drexel University College of Medicine. When administered to newborn rats immediately after head injury, the FDA-approved antibiotic minocycline exacerbated cognitive deficits, says the study, which was published in the journal Experimental Neurology.

"The developing brain is not the same as the fully mature brain," said Ramesh Raghupathi, PhD, a professor of neurobiology and anatomy in the College of Medicine. "This study suggests that acute interventions targeting the inflammatory cascade may not be a viable strategy for treating in infants and young children."

The drug minocycline works by decreasing the activation of microglia—the primary immune cells in the brain and spinal cord that protect against foreign pathogens. Inhibiting microglia appears to be an effective strategy to prevent long-term brain damage, since studies have shown an association between increased activity of these cells and neuron degeneration. And repurposing FDA-approved drugs to fit a new medical need is a desirable approach.

"In the pediatric animal model, we saw a microglia response that resembled what you would see in an adult brain. There was a lot of cell death, damage and inflammation," Raghupathi said. "You would hypothesize that if you block the microglia activity, you would see an improvement in function."

But when Raghupathi and his team treated the newborn rats with minocycline—one dose every day for three days—they saw that their brain activity did not improve. When the researchers increased the dosage to nine days instead of three, the animal models showed significant memory problems and other behavioral deficits.

Raghupathi believes the antibiotic had an adverse effect on the neonate rats, because microglia plays an important role during : These cells clear out dead neurons and debris to make a path for surviving neurons to function normally. By targeting the microglia in the pediatric animal model, the antibiotics seemed to prevent the brain from undergoing its natural maturation process.

"You can think of microglia in a developing brain like a garden rake that clears debris out of the lawn to make sure the grass grows properly," Raghupathi said. "By removing the dead cells, it paves the way for the to rewire itself."

While treating acute inflammation in the pediatric brain may not be effective, the researchers hypothesize that extending the window of intervention could have more positive outcomes.

In upcoming studies, they plan to wait two or three weeks after injury to administer the minocycline, giving the pediatric brain more time to develop before receiving treatment.

"We think that long-term inflammation may be the target," Raghupathi said.

Explore further: 'Housekeepers' of the brain renew themselves more quickly than first thought

More information: L.A. Hanlon et al, Differential effects of minocycline on microglial activation and neurodegeneration following closed head injury in the neonate rat, Experimental Neurology (2017). DOI: 10.1016/j.expneurol.2016.12.010

Related Stories

'Housekeepers' of the brain renew themselves more quickly than first thought

January 10, 2017
A study, led by the University of Southampton and published in Cell Reports, shows that the turnover of the cells, called Microglia, is 10 times faster, allowing the whole population of Microglia cells to be renewed several ...

Rejuvenating the brain's disposal system

December 21, 2016
A characteristic feature of Alzheimer's disease is the presence of so called amyloid plaques in the patient's brain - aggregates of misfolded proteins that clump together and damage nerve cells. Although the body has mechanisms ...

Experimental drug shows promise in treating Alzheimer's disease

October 25, 2016
An experimental drug shows promise in treating Alzheimer's disease by preventing inflammation and removing abnormal protein clumps in the brain that are associated with the disease, suggests a study in mice presented at the ...

The brain needs cleaning to stay healthy

May 26, 2016
Research led by the Achucarro Basque Center for Neuroscience, the University of the Basque Country (UPV/EHU), and the Ikerbasque Foundation has revealed the mechanisms that keep the brain clean during neurodegenerative diseases.

The brain may show signs of aging earlier than old age

March 18, 2016
A new study published in Physiological Genomics suggests that the brain shows signs of aging earlier than old age. The study found that the microglia cells—the immune cells of the brain—in middle-aged mice already showed ...

Study explains mechanisms behind glioblastoma influence on the immune system

September 12, 2016
Glioblastomas exert an influence on the microglia, immune cells of the brain, which causes them to stimulate cancer growth rather than attacking it. In a study published in the journal Nature Immunology, an international ...

Recommended for you

Discovery deepens understanding of brain's sensory circuitry

December 12, 2017
Because they provide an exemplary physiological model of how the mammalian brain receives sensory information, neural structures called "mouse whisker barrels" have been the subject of study by neuroscientists around the ...

Stuttering: Stop signals in the brain disturb speech flow

December 12, 2017
One per cent of adults and five per cent of children are unable to achieve what most of us take for granted—speaking fluently. Instead, they struggle with words, often repeating the beginning of a word, for example "G-g-g-g-g-ood ...

Intermittent fasting found to increase cognitive functions in mice

December 12, 2017
(Medical Xpress)—The Daily Mail spoke with the leader of a team of researchers with the National Institute on Aging in the U.S. and reports that they have found that putting mice on a diet consisting of eating nothing every ...

Neuroscientists show deep brain waves occur more often during navigation and memory formation

December 12, 2017
UCLA neuroscientists are the first to show that rhythmic waves in the brain called theta oscillations happen more often when someone is navigating an unfamiliar environment, and that the more quickly a person moves, the more ...

How Zika virus induces congenital microcephaly

December 12, 2017
Epidemiological studies show that in utero fetal infection with the Zika virus (ZIKV) may lead to microcephaly, an irreversible congenital malformation of the brain characterized by an incomplete development of the cerebral ...

Presurgical imaging may predict whether epilepsy surgery will work

December 11, 2017
Surgery to remove a part of the brain to give relief to patients with epilepsy doesn't always result in complete seizure relief, but statisticians at Rice University have developed a method for integrating neuroimaging scans ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.