Weill Cornell Science Briefs: October-November 2008

Nov 17, 2008


Traumatic Brain Injury, A New Point of View

Alternative Brain Scanning Technology May Aid Diagnosis

Researchers have found new evidence linking losses in memory and attention to subtle forms of brain damage following mild traumatic brain injury (TBI), which may eventually help in diagnosing when a routine concussion might lead to lasting cognitive problems. TBI affects more than 500,000 Americans each year and over 70 percent of these injuries are considered "mild," usually due to a concussion. Fifteen to 30 percent of these patients will suffer long-term impairments of memory and attention. The findings are published online and in the December issue of the journal BRAIN.

Following a head injury, patients who experience a concussion often show no signs of damage in a traditional CT or MRI scan, pass a basic neurological exam, and are then sent home with no additional treatment or follow-up. However, many such patients continue to report symptoms weeks and even months later, such as loss of concentration or memory loss — termed post-concussive syndrome.

The researchers studied diffusion tensor imaging (DTI), an advanced type of MRI scan that allows experts to view the microscopic motion of water molecules within the brain's white matter, the tissue that connects and allows communication between different brain centers. The group found that injury was visible in the subjects' memory and attention networks of the brain, but not visible via conventional MRI scans. The team, including researchers from Weill Cornell Medical College and University of California at San Francisco, identified two particular white-matter tracts, one strongly associated with attention and the other memory, in the brains of normal adults and adults with mild TBI.

For the first time, new research demonstrates that curbing harmful antioxidant processes in the brain's vasculature can reverse some of the cognitive decline associated with Alzheimer's disease. A natural enzyme of the immune system — NADPH oxidase — has been found to have toxic side effects, producing free radicals in the brains of mice. Identification of the enzyme's role in dementia might translate into a new drug target for Alzheimer's disease in humans, according to new findings published in a recent issue of the Proceedings of the National Academy of Sciences. After the offending enzyme was genetically "switched off," mice with a type of dementia mimicking Alzheimer's regained important cognitive abilities, even though the amount of Alzheimer's-linked amyloid plaques in their brains remained unchanged. These results suggest that the enzyme independently influences the progression of dementia.

Dr. Bruce McCandliss, corresponding author and associate professor of psychology in psychiatry at Weill Cornell Medical College, and co-first authors Sumit Niogi of Weill Cornell and Dr. Pratik Mukherjee of UCSF believe that these findings might be the first step toward clinical trials that will determine whether DTI may one day be used for early and accurate diagnosis in patients following TBI.

Since DTI is conducted with an MRI scanner, no additional equipment or cost is needed to collect such data. However, the researchers say that analyzing and interpreting the data is more complex, and tools for clinical diagnosis are still under development.

Contributing authors include Dr. Jamshid Ghajar, Dr. Minah Suh and Rachel Kolster, from Weill Cornell Medical College; and Dr. Geoffrey T. Manley and Hana Lee, from the University of California, San Francisco. The work was funded by a grant from the J.S. McDonnell Foundation.

Herb Studied for Enlarged Prostate

Saw Palmetto Therapeutic for Urinary Symptoms?

Physician-scientists are studying an herbal supplement that might aid in reducing the symptoms of an enlarged prostate in men. Recent figures show that benign prostatic hyperplasia (BPH) occurs in an estimated 50 percent of men over the age of 50 and in 75 percent of men 80 and older.

The research team, led by Dr. Steven A. Kaplan, professor of urology at Weill Cornell Medical College and attending urologist at NewYork-Presbyterian Hospital/Weill Cornell, will study the affects of using saw palmetto extract compared to a placebo, with the hope of reducing the symptoms of BPH. Symptoms include difficulty starting a urine stream (hesitancy and straining), decreased strength of the urine stream (weak flow), feeling that the bladder is not completely empty, an urge to urinate again soon after urinating and pain during urination (dysuria).

It is theorized that compounds called phytosterols, found in saw palmetto, might prevent prostate enlargement. Experts believe that prostate swelling may be caused by a rise in dihydrotestosterone (DHT) — a testosterone derivative involved in prostate growth — over a male's lifespan, especially during middle age. Scientists are unclear as to what causes the hormone to rise with time. However, escalating estrogen within the body has been correlated with, but has not been proven to be, directly promoting BPH. Like a basketball player blocking a shot from going into a basket, phytosterols in saw palmetto might block natural estrogen from binding to receptors in the body.

New Malaria Target

Researchers Discover Weakness in Malaria-Causing Parasite

Scientists may have found a promising new drug target on the parasite that causes malaria — P. falciparum. To survive, the parasite creates a tiny pore called an anion channel, through which it takes in nutrients from outside the host cell's membrane and excretes its waste. In a recent paper published in PLoS Pathogens, the authors describe for the first time how this channel functions and how to possibly impair that function — thereby sickening and killing the parasite. The researchers discovered an important regulatory subunit enzyme, called PfPKA-R, which is encoded in the parasite's genome, and appears to be key to the proper function of the anion channel. Medications to treat malaria exist but the parasite gradually develops resistance, making the ongoing search for new and better treatments imperative. The study was an international collaboration — led by Dr. Kirk Deitsch of Weill Cornell Medical College in New York City and Stéphane Egée of Université Pierre et Marie Curie, in Roscoff, France.

Newly Discovered Protein May Help Explain Tuberculosis' Resiliency

Experts Find Another Reason Why the Bacterium Is So Nasty

Weill Cornell scientists have located a protein produced by the tuberculosis bacterium that may tell researchers more about how the invader lives so resiliently inside of the body. Dr. Benjamin Gold, working with Dr. Carl Nathan, chairman of microbiology and immunology at Weill Cornell Medical College and their colleagues, located a protein called mycobacterial metallothionein (MymT), which acts like a shield to protect the tuberculosis bacterium from the body's natural defenses.

The tuberculosis bacterium lurks within cells called macrophages — immune system cells that bombard harmful microbes with a soup of chemicals, including nitric oxide. The researchers believe that the newly discovered protein helps the bacterium resist a newly discovered action of nitric oxide, thus allowing the infection to stay strong within the body. The Weill Cornell scientists discovered nitric oxide can liberate copper from proteins within the bacterium, and may also reduce it from a relatively harmless form to lethal form. The new protein, MymT, binds the copper to protect the bacterium from being poisoned by the metal.

All the genetic information in the tuberculosis organism was sequenced in 1998. Yet the gene encoding MymT was overlooked until now because of its very small size and the novel way it encodes the protein. Thus, this study suggests that there may be other genes in bacterial pathogens that contribute to their potential to cause disease, but which have otherwise been overlooked, including relatives of MymT.

The study is published in a recent issue of the journal Nature Chemical Biology.

NewYork-Presbyterian Hospital/Weill Cornell Medical Center

NewYork-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian and Weill Cornell Medical College, the medical school of Cornell University. NewYork-Presbyterian/Weill Cornell provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, education, research and community service. Weill Cornell physician-scientists have been responsible for many medical advances — from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial for gene therapy for Parkinson's disease, the first indication of bone marrow's critical role in tumor growth, and, most recently, the world's first successful use of deep brain stimulation to treat a minimally-conscious brain-injured patient. NewYork-Presbyterian, which is ranked sixth on the U.S.News & World Report list of top hospitals, also comprises NewYork-Presbyterian Hospital/Columbia University Medical Center, Morgan Stanley Children's Hospital of NewYork-Presbyterian, NewYork-Presbyterian Hospital/Westchester Division and NewYork-Presbyterian Hospital/The Allen Pavilion. Weill Cornell Medical College is the first U.S. medical college to offer a medical degree overseas and maintains a strong global presence in Austria, Brazil, Haiti, Tanzania, Turkey and Qatar. For more information, visit www.nyp.org and www.med.cornell.edu.

Media Contact:

Andrew Klein