@misc{10498/30595,
year = {2018},
month = {9},
url = {http://hdl.handle.net/10498/30595},
abstract = {Brain injuries in the adult mammalian brain are accompanied by a fast neurogenic response inside neurogenic niches. However, this response does not contribute to the generation of new neurons within damaged tissues like the cerebral cortex, which are essentially non-neurogenic. This occurs because injuries create a hostile environment that favors gliogenesis. Overexpression and sequential activation of the ADAM17/TGFα/EGFR signaling cascade are crucial for the generation of this gliogenic/non-neurogenic environment. Here, we demonstrate that chronic local infusion of a general metalloprotease inhibitor in areas of traumatic cortical injury in adult mice moderately increased the number of neuroblasts around the lesion, by facilitating the survival of neuroblasts and undifferentiated progenitors, which had migrated to the perilesional area from the subventricular zone. Next, we generated a dominant-negative version of ADAM17 metalloprotease, consisting of a truncated protein containing only the pro-domain (ADAM17-Pro). Specific inhibition of ADAM17 activity by ADAM17-Pro overexpression increased the generation of new neurons in vitro. Local overexpression of ADAM17-Pro in injured cortex in vivo, mediated by lentiviral vectors, dramatically increased the number of neuroblasts observed at the lesion 14 days after injury. Those neuroblasts were able to differentiate into cholinergic and GABAergic neurons 28 days after injury. We conclude that ADAM17 is a putative target to develop new therapeutic tools for the treatment of traumatic brain injury.},
publisher = {Nature Publishing Group},
keywords = {neurogenesis},
keywords = {traumatic brain injury},
keywords = {neuroblast migration},
keywords = {ADAM17},
title = {Specific inhibition of ADAM17/TACE promotes neurogenesis in the injured motor cortex},
doi = {10.1038/s41419-018-0913-2},
author = {Geribaldi Doldán, Noelia and Carrasco Viñuela, Manuel and Murillo Carretero, Maribel and Domínguez García, Samuel and García Cózar, Francisco José and Muñoz Miranda, Juan Pedro and del Río García, Valme and Verástegui Escolano, Cristina and Castro González, Carmen},
}