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Engineering advanced neural tissue constructs to mitigate acute cerebral inflammation after brain transplantation in rats

Liaudanskaya, Volha, Jgamadze, Dennis, Berk, Alexander N., Bischoff, David J., Gu, Ben J., Hawks-Mayer, Hannah, Whalen, Michael J., Chen, H. Isaac, Kaplan, David L.
Biomaterials 2019 v.192 pp. 510-522
adrenal cortex hormones, animal tissues, brain damage, cell death, engineering, immune system, inflammation, methylprednisolone, motor cortex, neural stem cells, neurons, rats, silk, stroke
Stroke, traumatic brain injuries, and other similar conditions often lead to significant loss of functional brain tissue and associated disruption of neuronal signaling. A common strategy for replacing lost neurons is the injection of dissociated neural stem cells or differentiated neurons. However, this method is unlikely to be suitable for replacing large brain cavities, and the resulting distribution of neurons may lack the necessary architecture to support appropriate brain function. Engineered neural tissues may be a viable alternative. Cell death is a prominent concern in neuronal grafting studies, a problem that could be magnified with the transplantation of engineered neural tissues. Here, we examined the effect of one contributor to cell death, acute cerebral inflammation, on neuronal survival after the transplantation of bioengineered constructs based on silk scaffolds. We found evidence of a high degree of inflammation and poor neuronal survival after introducing engineered constructs into the motor cortex of rats. Integrating a corticosteroid (methylprednisolone) into the constructs resulted in significantly improved neuron survival during the acute phase of inflammation. The improved construct survival was associated with decreased markers of inflammation and an anti-inflammatory state of the immune system due to the steroid treatment.