Researchers have developed a method which they say could turn non-neuronal cells in the brain into neurons, limiting the impact of stroke.
Currently, stroke patients are treated by restoring proper blood flow to their neurons. However, these neurons are often dead by the time treatment is given.
Replacing dead neurons is therefore an ideal but very difficult strategy to regain loss of brain function.
Now, researchers at Okayama University have now developed a method of converting non-neuronal cells in the brain into neurons for this purpose.
Ascl1, Sox2, and NeuroD1 are proteins found within neurons. When they are introduced tactically into ordinary cells, the cells start showing neuron-like properties.
The research team led by Professor ABE Koji and Senior Lecturer Yamashita Toru designed their studies based on this principle.
Small silicon filaments were first inserted into specific blood vessels within the brains of mice. These filaments clogged the vessels and restricted blood flow thereby giving the mice a stroke.
Three days after a stroke was induced, a delivery system comprising a weakened virus was used to inject Ascl1, Sox2, or NeuroD1 into the damaged brain areas.
Viral systems usually attack rapidly-diving, younger cells, and not mature cells like neurons. This gave the team tight control over the type of cells the virus would enter and deposit the proteins into.
Indeed, it was observed that protective, non-neuronal cells called as glial cells were the ones targeted successfully.
Three weeks after the viral injection, these glial cells started presenting markers typically found in young neurons. Forty-nine days after the injection these cells had characteristics of mature neurons, including the branching pattern typical to neurons.
The injection of Ascl1, Sox2, or NeuroD1 successfully led to the generation of “new” neurons.
The researchers also analysed behavioural patterns of these mice to assess their mobility post stroke. However, in spite of brain cell regeneration their movement was not completely restored.
“Taken together, the present study successfully achieved, for the first time, in vivo direct reprogramming by enforced transcriptional factors (Ascl1, Sox2 and NeuroD1) in the post-stroke mouse brain”, conclude the authors.
