Fall 2005

Questions Lead Neurointensivist Back to Lab

For many neurologists specializing in stroke, the past decade has been liberating. Emergency stroke treatment has become a reality since the Food and Drug Administration (FDA) approval of anti-ischemic agents and devices. Although neurointensivist Vineeta Singh, M.D., has felt that excitement, she also has been frustrated.

"I've had the best training available for treating stroke, but every time I turn around there are unanswerable questions about the best way to deal with something," Singh says. "In the ICU, things are happening in real time and you have to make decisions. The problem is that so often we don't have the information we need to make those decisions."

One example faced by many neurologists in the ER — once it has been established that the patient is suffering from ischemic stroke, how does one really know whether or not it would be beneficial to administer tissue plasminogen activator (tPA)? The guidelines say that tPA has to be administered within three hours of the onset of stroke, but often there is no objective way to tell how much time has passed. "Many times you are relying on the patient's family, which may not have noticed when symptoms first started, or may simply have found the patient on the floor," Singh says.

Furthermore, the three-hour limit is not absolute in actual practice. "The three-hour time limit is based on animal data, but on the clinical side it's quite clear that there are cases where tPA might help after even eight hours," Singh says. "Patients might come in with just numbness in their hands and then hours later have a much larger stroke."

"We have cutting-edge therapy, but when so much is at stake, we are relying on secondhand, nonscientific information," Singh says. Why and when the brain recovers from stroke also are fraught with uncertainty. "When families ask after a stroke if the patient will improve, I sometimes feel uncomfortable answering, because often we don't really know," Singh says.

An attending neurologist on the neurovascular service at UCSF, Singh realized that the answers to her questions were not going to come from the clinic. Her frustration led her back to the laboratory, where she hopes to get hard information about what happens to brain cells during and after stroke.

Previous research on the cellular response to stroke has been done mostly in the hippocampus, where the cells are neatly lined up and easy to study. Singh chose to study dopamine neurons in the midbrain after making a key observation. "For days after stroke, people look and act stunned," Singh says. "You would think that if they had only stroke-induced aphasia, they would still want to get up and move around, but they don't." Singh hypothesizes that the stunned affect, and the much written-about poststroke depression, may be connected to effects on dopamine neurons.

Singh's experiments involved bathing portions of rat midbrain slices in a medium that could be either saturated with oxygen or made anoxic. A microprobe allowed her to measure the activity of individual cells.

When deprived of oxygen and glucose for only a brief, five-minute period, the excitatory synapses decrease their activity dramatically for an extended period. "This is telling you that the excitatory synapses in this brain region are less active in the immediate aftermath of ischemia," Singh says. It is not proven whether these changes are responsible for the "stunned look" in stroke patients and whether it has any effect on stroke recovery. Singh hypothesizes that this phenomenon is likely to be neuroprotective due to its similarity to a very well-described phenomenon known as ischemic preconditioning.

The other major goal of her research is to find biological markers that can reliably give physicians an objective picture of how long ago the ischemic attack began, how severe it is and what the likely outcomes are. Ultimately, the answers may lead to improved care for stroke patients.

To contact Dr. Singh, call (415) 353-1489.

Related Information

News Releases

UCSF Probes Stem Cells, Links With Disease
Scientists are studying the earliest stages of embryonic and adult stem cell growth to identify genetic missteps that cause neurological diseases such as as amyotrophic lateral sclerosis (ALS), cancer, birth defects and infertility.

Standardized Guidelines Improve Stroke Care
Patients suffering from a stroke are more likely to have improved outcomes and fewer complications when hospitals use standardized guidelines for care during a patient's admission and discharge, according to a study led by UCSF Medical Center researchers.