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From the article:

In the face of low brain oxygen that can occur with stroke or other brain injury, these astrocytes, star-shaped brain cells that help give the brain its shape and regularly provide fuel and other support to neurons, should become “highly reactive,” increasing cell signaling, releasing neuroprotective factors and clearing neurotoxins, scientists report in The Journal of Neuroscience.


To try to understand how astrocytes take on this enhanced role, they knocked out the enzyme aromatase, which is critical to estrogen production, in neurons in the forebrain, the largest region of the human brain, in their animal model.

They found that one way estrogen made by neurons is protective in ischemia is by suppressing signaling of the fibroblast growth factor, FGF2, which is also made by neurons and known to suppress astrocyte activation, Brann and his colleagues write. Normally neurons use this FGF2 brake to help keep astrocyte response from getting out of control.


In this scenario, when they used a neutralizing antibody to block FGF2, astrocytes became more active and neuron damage was decreased. “The astrocyte activation came back and we saw the protective growth factors that they make,” Brann says. Giving more estrogen produced similar benefits, including improving cognition after ischemia.


They also saw less of known neuroprotective growth factors, like brain derived neurotrophic factor and insulin-like growth factor 1, which astrocytes normally release at an increased rate in response to a stressor like ischemia, and more suppressive substances like the brake FGF2 [when the estrogen producing enzyme aromatase was knocked out].


Activated astrocytes also help clear glutamate, the brain’s most abundant excitatory neurotransmitter that normally helps neurons communicate. But without estrogen from the neurons, the glutamate transporter, GLT-1, which removes about 90% of the glutamate, is significantly decreased and the chemical can accumulate at toxic levels in the brain and become a major cause of neuron destruction. “Glutamate is essential for brain function, but if it’s overproduced, it’s brain toxic,” Brann says.

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