Scientists from Emory University School of Medicine says that clot-busting stroke drug tPA can act as a neuroprotectant and may form the keystone of an adaptive response to a reduction in blood flow.
In a new study, the boffins have shown that certain parts of the brains of mice lacking the gene for tPA are more vulnerable to stroke. In addition, tPA can protect neurons in the same part of the brain from the stress of hypoxia (low oxygen).
The results are published online in the Journal of Clinical Investigation.
"tPA is not only a drug, it is a natural protein produced in response to hypoxia," says senior author Manuel Yepes, MD, associate professor of neurology at Emory University School of Medicine. "If you look at the parts of brain where the gene for tPA is turned on the most, one of these is the hippocampus. It is well known that the hippocampus is especially vulnerable to hypoxia compared with other regions of the brain. We believe there is a reason for this overlap."
The hippocampus is a structure in the middle of the brain thought to be responsible for memory formation. In mice lacking the gene for tPA, neurons in the hippocampus are more vulnerable to dying after a short simulated stroke lasting 20 minutes, Yepes and his colleagues found. In the laboratory, pre-treatment with tPA protects hippocampal neurons in culture from hypoxia. In contrast, tPA has the opposite effect on neurons from the cortex.
tPA's protective properties suggest that it may be playing a role in a process called "ischemic preconditioning," where a less-than-lethal stroke can protect the brain against a later repeat, Yepes says. tPA's effects on the blood-brain barrier can be seen as a way to get more blood to a deprived part of the brain.