Establishing a non-human primate model for glial scar reversing and brain repair

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  Reactive gliosis is a common pathological hallmark widely associated with brain injury,stroke,glioma,and neurodegenerative disorders such as Alzheimers disease.Reactive astrocytes initially exert neuroprotective effects but later form glial scars to inhibit neuronal growth.Currently,there is no effective way to reverse glial scars back to normal neural tissue.We have recently developed an innovative in vivo reprogramming technology to directly convert reactive astrocytes into functional neurons inside the mouse brain(Guo et al.,Cell Stem Cell,2014).This is achieved through in vivo expression of a single neural transcription factor NeuroD1 in the reactive astrocytes in injured mouse brain or model animals for Alzheimers disease.Our in vivo direct cell conversion technology will not only reduce the number of reactive astrocytes,but also generate new neurons simultaneously at the injury site,making it possible for the first time to reverse glial scar back to neural tissue.In order totranslate our new technology into a potential therapy for human patients,we have decided to further test this new technology for brain repair in nonhuman primate models.We have developed several brain injury models in rhesus monkeys,including brain stab injury,ischemic stroke,and hemorrhagic stroke models.We found that all these injury models resulted in significant glial scars in the monkey cortex.However,different from rodent models,the time course of glial scar formation is very slow,suggesting the necessity of using non-human primates to mimic human brain injury.Our glial scar reversing technology will have the potential to be developed into an unprecedented therapy to treat brain injury including stroke,and neurodegenerative disorders such as Alzheimers disease and Parkinsons disease.
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