Aditya Dutta Gupta

Introduction. The treatment of traumatic brain injury through neural stem cell treatment has been heavily limited by the hostility of the transplantation microenvironment. The growth of NSCs is mediated by the three Wnt pathways, of which one is canonical and two are non-canonical.¹ The canonical pathway focuses on the stabilization of the β-catenin protein, which is otherwise destabilized by a destruction complex formed by APC, AXIN, GSK3β, and CK1. Stabilization of the β-catenin gene allows downstream upregulation of Wnt signaling gene products that involve axis patterning, cell fate specification, cell proliferation, and cell migration.²There are methods to enhance this canonical pathway, including upregulating glucocerebrosidase, inhibiting miRNA-148b, and hypoxia induction. Methods. For these experiments, NSCs were transplanted into mice that were given a traumatic brain injury, with motor coordination tested using a Rotarod.³ Immunohistochemistry with confocal laser scanning microscopy was used for analysis, as well as transplantation of NSCs. The assessment of Wnt/β-Catenin antagonism was conducted in vivo through protein markers Dkk1 and Wnt1-Ab.³ Results. NSC treatment with glucocerebrosidase reduced cerebral infarct volume in a statistically significant manner. Bcl-2 expression was suppressed in NSC and glucocerebrosidase treated mice and this reduced apoptotic death of cells.⁴ Mice treated with NSC and glucocerebrosidase also preserved mitochondrial ultrastructure amidst injury. Similar results were obtained upon miRNA-148b inhibition and hypoxia induction.⁵ Conclusion. It is necessary to properly regulate the hostile microenvironment in ischemic brain injury for efficacious NSC transplantation as a therapy. In order to alleviate the conditions, glucocerebrosidase, miRNA-148b inhibition, and the advantageous pre-existing condition of hypoxia are factors we can utilize to minimize the hostility of the microenvironment.

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5. Ge, H., Zhang, C., Yang, Y. et al. Ambroxol Upregulates Glucocerebrosidase Expression to Promote Neural Stem Cells Differentiation Into Neurons Through Wnt/β-Catenin Pathway After Ischemic Stroke, Frontiers in Molecular Neuroscience, VOLUME 13, 2021, pg. 263 https://www.frontiersin.org/article/10.3389/fnmol.2020.596039