Research Update


Researchers have found measurable brain changes in children after a single season of playing youth football, even without a concussion diagnosis, according to a study published online in the journal Radiology.

WhitlowAccording to USA Football, there are approximately 3 million young athletes participating in organized tackle football across the country. Numerous reports have emerged in recent years about the possible risks of brain injury while playing youth sports and the effects it may have on developing brains. However, most of the research has looked at changes in the brain as a result of concussion.

“Most investigators believe that concussions are bad for the brain, but what about the hundreds of head impacts during a season of football that don’t lead to a clinically diagnosed concussion? We wanted to see if cumulative sub-concussive head impacts have any effects on the developing brain,” said the study’s lead author, Christopher T. Whitlow, MD/PhD ’04, MHA, associate professor and chief of neuroradiology at Wake Forest Baptist.

The brain’s white matter is composed of millions of nerve fibers called axons that act like communication cables connecting various regions of the brain. Diffusion tensor imaging produces a measurement, called fractional anisotropy (FA), of the movement of water molecules in the brain and along axons. In healthy white matter, the direction of water movement is fairly uniform and measures high in FA. When water movement is more random, FA values decrease, which has been associated with brain abnormalities in some studies.

The results showed a significant relationship between head impacts and decreased FA in specific white matter tracts and tract terminals, where white and gray matters meet.

“We found that these young players who experienced more cumulative head impact exposure had more changes in brain white matter, specifically decreased FA, in specific parts of the brain,” Whitlow said. “These decreases in FA caught our attention, because similar changes in FA have been reported in the setting of mild TBI.”

The research was supported in part by the Childress Institute for Pediatric Trauma at Wake Forest Baptist.

Pilot Study Finds Promise for Alleviating Symptoms in Athletes

A small pilot study of male and female high school- and college-age athletes found improvement in persisting post-concussion symptoms after undergoing High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM®).

TegelerHIRREM is a technology developed by and licensed to Brain State Technologies, of Scottsdale, Ariz. It uses software algorithms to translate the brain’s electrical frequencies into audible tones of variable pitch and timing. These “brain sounds” are mirrored to the user in real time via ear buds, permitting the brain to continuously update itself with respect to its own activity patterns, resulting in auto-calibration or self-optimization, typically with shifts toward improved balance and reduced hyperarousal.

“Until now there has been little to provide relief for the 10 to 15 percent of athletes with concussion symptoms that last three weeks or more,” said Charles H. Tegeler, MD, professor of neurology and principal investigator of the study. “These symptoms can include headache, dizziness, insomnia, depression, anxiety, irritability, exercise intolerance, and lack of focus and concentration to the point where normal function is affected.”

Wake Forest Baptist’s research, published in the journal Sports Medicine Open, followed 15 male and female students who had a concussion while participating in baseball, basketball, cheerleading, cycling, football, gymnastics, lacrosse, snowboarding and soccer, and afterward developed symptoms that did not resolve after three to four weeks—a normal recovery period.  Symptoms had persisted on average for 4.6 months after their most recent concussion.

Tegeler described the study, although limited in size, as “significant because the participants not only had reduced symptoms and other objective improvements, but most were able to get back to play.”

This study was supported by a research grant from the Susanne Marcus Collins Foundation Inc.

Routine Test for Kidney Function Proves Valuable for Stroke Patients

A routine blood test that measures kidney function can be a valuable predictor of short-term outcomes for stroke patients, according to a study led by a neurologist at Wake Forest Baptist.

El Husseini“Kidney disease is frequently a comorbidity in patients with acute ischemic stroke,” said Nada El Husseini, MD, assistant professor of neurology and the principal investigator of the study, which was published in February in the journal Stroke.

“This one test done on admission to measure kidney function can be used to better inform patients with ischemic stroke and their families about what to expect.”

The study team analyzed data on more than 232,000 ischemic stroke patients age 65 and older who were admitted to 1,581 U.S. hospitals over three years. The researchers found that those patients with renal dysfunction upon admission, as indicated by the estimated glomerular filtration rate (eGFR) calculated from a blood creatinine test and basic demographic information such as age, race and sex, were significantly more likely to die while hospitalized and far less likely to be discharged home.

The researchers found that in-hospital mortality was most common (29.2 percent) among the stroke patients with eGFR scores 15 and under without dialysis and least common (9.1 percent) among those with scores 60 and above.

Brain Volume Predicts Successful Weight Loss in the Elderly

Wake Forest Baptist scientists believe they may have found a way to predict who will be successful in their weight-loss efforts by using a quick, noninvasive brain scan.

BurdetteIn findings from a small study published online in the journal Obesity, the researchers were able to predict weight loss success with 78 percent accuracy based on the brain volume of the study participants.

“A simple test that can predict intentional weight loss success using structural brain characteristics could ultimately be used to tailor treatment for patients,” said Jonathan Burdette, MD, professor of radiology and co-author of the study.

“For example, people identified at high risk for failure might benefit from intensive treatment and close guidance. People identified as having a high probability for success might best respond to less-intensive treatment.”

The study’s small sample size was a limitation, Burdette said, but the researchers hope to include more people in follow-up studies and broaden the types of interventions to help improve the predictive nature of the test.

Scientists Report on Safe, Nonaddictive Pain-killing Compound in Animal Model

Since the isolation of morphine from opium in the 19th century, scientists have hoped to find a potent opioid analgesic that isn’t addictive and doesn’t cause respiratory arrest with increased doses.

Now scientists at Wake Forest Baptist report that in an animal model a novel pain-killing compound, BU08028, is not addictive and does not have adverse respiratory side effects like other opioids. The research findings were published online in August in the Proceedings of the National Academy of Sciences.

“Based on our research, this compound has almost zero abuse potential and provides safe and effective pain relief,” said Mei-Chuan Ko, PhD, professor of physiology and pharmacology at Wake Forest Baptist and lead author of the study. “This is a breakthrough for opioid medicinal chemistry that we hope in the future will translate into new and safer, nonaddictive pain medications.”

Protein Identified that Restores Effectiveness of Common Breast Cancer Treatment

Estrogen-receptor-positive (ER+) is the most common type of breast cancer, and drugs used to treat this cancer, such as tamoxifen and Faslodex, block the hormone estrogen receptor that ER+ cancer cells need to grow.

CookOne problem with these treatments is that many tumors initially responsive to the drugs develop resistance, making the medicines less effective. Scientists at Wake Forest Baptist have succeeded in enhancing and restoring sensitivity to an estrogen-blocking drug in ER+ tumors in an animal model. The research findings were published in Cancer Research.

Previous research showed that glucose-regulated protein 78 (GRP78) is elevated in breast cancer tumors and that targeting it could enhance and restore sensitivity in estrogen targeted therapy-resistant cells in vitro. In this study, the researchers sought to determine if they could target GRP78 in breast cancer tumors in an animal model.

They first tested a GRP78-targeting molecule called a morpholino, which can modify gene expression. The morpholino successfully inhibited GRP78 and restored sensitivity to tamoxifen in the resistant tumors.

“Morpholinos are candidate drugs already being used to target other proteins in clinical trials to treat prostate cancer, but this is the first time inhibiting the gene expression of GRP78 with these agents may have potential to overcome resistance to chemotherapy,” said Katherine Cook, PhD ’10, assistant professor and the study’s lead author.

Acupuncture Reduces Hot Flashes for Half of Women in Study

Hot flashes—the bane of existence for many women during menopause—can be reduced in frequency by almost half for about 50 percent of women over eight weeks of acupuncture treatment, according to scientists at Wake Forest Baptist.

AvisIn a study published in September in the journal Menopause, scientists reported that about half the women in the study reduced the frequency of hot flashes, while half did not.

“Women bothered by hot flashes and night sweats may want to give acupuncture a try as a relatively low-cost, low-risk treatment,” said Nancy Avis, PhD, lead author of the study and professor of Public Health Sciences at Wake Forest School of Medicine. “Women will know pretty quickly if acupuncture will work for them. Women who had a reduction in their hot flashes saw a benefit beginning after about three to four weeks of weekly treatments.”