Journal of neurotrauma
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Journal of neurotrauma · Mar 2018
Intranasally Delivered Wnt3a Improves Functional Recovery after Traumatic Brain Injury by Modulating Autophagic, Apoptotic and Regenerative Pathways in the Mouse Brain.
Traumatic brain injury (TBI) is a prevalent disorder, but no effective therapies currently exist. An underlying pathophysiology of TBI includes the pathological elevation of autophagy. β-Catenin, a downstream mediator of the canonical Wnt pathway, is a repressor of autophagy. The Wnt/β-catenin pathway plays a crucial role in cell proliferation and neuronal plasticity/repair in the adult brain. ⋯ This chronic Wnt3a therapy augmented neurogenesis (0.52 ± 0.09 and 1.25 ± 0.13 BrdU+/NeuN+ co-labeled cells in TBI+Saline mice and TBI+Wnt3a mice, respectively; p < 0.01, n = 6/group) and angiogenesis (0.26 ± 0.07 and 0.74 ± 0.13 BrdU+/GLUT1+ co-labeled cells in TBI+Saline and TBI+Wnt3a mice, respectively; p = 0.014, n = 6/group). The treatment improved performance in the rotarod test and adhesive removal test. Targeting the Wnt pathway implements a unique combination of protective and regenerative approaches after TBI.