A stroke is a condition in which the brain cells suddenly die because of a lack of oxygen. This can be caused by an obstruction in the blood flow, or the rupture of an artery that feeds the brain. The patient may suddenly lose the ability to speak, there may be memory problems, or one side of the body can become paralyzed.
The treatments for stroke are currently limited, patients are treated with emergency treatments (thrombolytic drugs), which leaves survivors with severe disabilities including loss of mobility, pain, numbness, memory loss, difficulty talking and impaired cognitive ability. Many of the regenerative medicine technologies in development are targeting the post-stroke rehabilitation period for which there are currently no therapies available.
The large, collaborative study of researchers found that astrocytes -- neural cells that transport key nutrients and form the blood-brain barrier -- can protect brain tissue and reduce disability due to stroke and other ischemic brain disorders.
Astrocytes are known as housekeeping cells because of their supportive roles to neurons.They are critical to several brain functions and protect neurons from injury and death. They are not excitable cells like neurons and are easier to harness.
Researchers started their study by using a transcription factor known as Olig2 to differentiate human embryonic stem cells into astrocytes. By this approach they generated a type of astrocyte called Olig2PC-Astros and the astrocytes produced are 100 percent pure.
They then compared the effects of Olig2PC-Astros with another type of astrocyte called NPC-Astros. They conduct their research on rat in three groups. One group was transplanted with Olig2PC-Astros, other with NPC-Astros and third group with no transplantation.
The rats transplanted with Olig2PC-Astros experienced superior neuroprotection together with higher levels of brain-derived neurotrophic factor (BDNF), a protein associated with nerve growth and survival. The rats transplanted with NPC-Astros or that received no treatment showed much higher levels of neuronal loss.
To determine whether the astrocytes impacted behavior, the researchers used a water maze to measure the rats' learning and memory. In the maze, the rats were required to use memory rather than vision to reach a destination. When tested 14 days after transplantation, the rats receiving Olig2PC-Astros navigated the maze in significantly less time than the rats that received NPC-Astros or no treatment.
The investigators used cell culture experiments to determine whether the astrocytes could protect neurons from oxidative stress, which plays a significant role in brain injury following stroke. They exposed neurons co-cultured with both types of astrocytes to hydrogen peroxide to replicate oxidative stress. They found that, while both types of astrocytes provided protection, the Olig2PC-Astros had greater antioxidant effects. Further investigation showed that the Olig2PC-Astros had higher levels of the protein Nrf2, which increased antioxidant activity in the mouse neurons.
The investigators also investigated the genetic qualities of the newly identified astrocytes and they were genetically similar to the standard NPC-Astros.
In addition to being therapeutically helpful, the Olig2PC-Astros showed no tumor formation, remained in brain areas where they were transplanted and did not differentiate into other cell types, such as neurons.
The results could lead to stem cell treatments for many neurodegenerative diseases.
The result is published in journal Nature Communications.
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