Experimental treatment halts hypoxic-ischemic brain injury i...( CINCINNATI Inhibiting an enzyme in ...)

CINCINNATI Inhibiting an enzyme in the brains of newborns suffering from oxygen and blood flow deprivation stops a type of brain damage that is a leading cause of cerebral palsy, mental retardation and death, according to researchers at Cincinnati Children's Hospital Medical Center.

Reporting their results in the Journal of Neuroscience, the scientists show blocking the brain enzyme, tissue-type plasminogen activator (tPA), prevents progressive brain damage triggered by the lack of oxygen and blood supply. The experimental pre-clinical treatment involved putting a naturally occurring substance called plasminogen activator inhibitor-1 (PAI-1) into the brains of newborn rats, said Chia-Yi Kuan, M.D. PhD, senior investigator on the study and a researcher in the divisions of Developmental Biology and Neurology at Cincinnati Children's.

Besides demonstrating the brain's plasminogen activator system plays a pivotal role in neonatal cerebral hypoxic-ischemic brain injury, Dr. Kuan said the study also shows this system may be a promising therapeutic target in infants suffering hypoxic-ischemic encephalopathy (HIE). Identification of a treatment target is a vital step to finding better ways to treat newborns with HIE.

"Not only is hypoxic-ischemic encephalopathy an important cause of perinatal mortality and permanent neurological morbidities, but there are no specific medications against HIE in current medical practice," explained Ton J. DeGrauw, M.D., Ph.D., director of Neurology at Cincinnati Children's. "This is why the findings of this study may have important clinical implications because, in a rodent model of HIE, they that show inhibiting plasminogen activators in functional areas of the brain is powerful strategy for brain protection."

Earlier studies have pointed to the role certain brain proteases, or enzymes, play in adult brain injury following stroke, but very little has been known about what these enzymes do in
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