Weill Cornell team discovers how brain's own tPA helps regulate blood flow ...( NEW YORK (Jan. 17 2008) -- The human...)

NEW YORK (Jan. 17, 2008) -- The human brain contains its own store of a powerful enzyme (and stroke drug) called tissue plasminogen activator (tPA), which appears to be a key regulator of blood flow to brain cells, a team at the Weill Cornell Medical College in New York City reports.

"We found that this natural tPA boosts blood flow to brain cells via its influence on nitric oxide synthase, which is essential to the production of nitric oxide (NO). NO is a well-known vasodilator -- a drug or chemical that widens blood vessels -- so, more NO means better blood flow to neurons as they become more active," explains study senior author Dr. Costantino Iadecola, the George C. Cotzias Distinguished Professor of Neurology and Neuroscience at Weill Cornell Medical College, and chief of the Division of Neurobiology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

The findings have just been published in this week's online issue of Proceedings of the National Academies of Science.

Besides elucidating the role of naturally produced tPA in neuronal blood flow, the new findings could have implications for the study of stroke and Alzheimer's disease. Both conditions are associated with marked declines in natural brain levels of tPA.

TPA has become a star of sorts in cardiovascular research over the past two decades, ever since scientists discovered its remarkable ability to break up clots.

"Essentially, tPA, a powerful protease enzyme, cleaves a protein called plasminogen into plasmin, an enzyme that quickly 'eats up' clots," notes study lead author Dr. Laibaik Park, instructor in neuroscience at Weill Cornell. For that reason, doctors often administer a shot of tPA to stroke patients within minutes or hours of an attack.

But other research had also detected tPA occurring naturally in the human brain, with levels of the enzyme rising as brain cell activity increased.

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