J Kent Werner1, Robert D Stevens. 1. aDepartments of Neurology bAnesthesiology Critical Care Medicine cNeurological Surgery, Johns Hopkins University School of Medicine.
Abstract
PURPOSE OF REVIEW: There is an urgent need for effective therapies to restore neurologic function and decrease disability following traumatic brain injury (TBI). Here, emerging findings on the mechanisms of post-TBI neural repair and regeneration, as well as therapeutic implications, are selectively reviewed. RECENT FINDINGS: Recent discoveries include the characterization of the inhibitory signaling systems within the injury site, postinjury stem cell niche activation, the role of serotonin signaling in repair, and environment enrichment. A potentially transformative finding has been the identification of exosomes, nano-sized extracellular vesicles which have key roles in cell signaling, and might serve as novel biomarkers and as vehicles for targeted delivery of repair-inducing molecules. SUMMARY: In the experimental setting, post-TBI repair can be promoted by modulation of inhibitory signaling, neurotrophic factor administration, and amplified serotonin signaling; additional strategies include mobilization of endogenous stem cell populations, exogenous cell-based therapies, and environmental enhancement. Feasibility, safety, and efficacy of these approaches need further investigation in humans. Studies are also needed to evaluate biomarkers based on molecular traces of neural repair and regeneration, which could transform prognostic and predictive modeling of post-TBI recovery trajectories.
PURPOSE OF REVIEW: There is an urgent need for effective therapies to restore neurologic function and decrease disability following traumatic brain injury (TBI). Here, emerging findings on the mechanisms of post-TBI neural repair and regeneration, as well as therapeutic implications, are selectively reviewed. RECENT FINDINGS: Recent discoveries include the characterization of the inhibitory signaling systems within the injury site, postinjury stem cell niche activation, the role of serotonin signaling in repair, and environment enrichment. A potentially transformative finding has been the identification of exosomes, nano-sized extracellular vesicles which have key roles in cell signaling, and might serve as novel biomarkers and as vehicles for targeted delivery of repair-inducing molecules. SUMMARY: In the experimental setting, post-TBI repair can be promoted by modulation of inhibitory signaling, neurotrophic factor administration, and amplified serotonin signaling; additional strategies include mobilization of endogenous stem cell populations, exogenous cell-based therapies, and environmental enhancement. Feasibility, safety, and efficacy of these approaches need further investigation in humans. Studies are also needed to evaluate biomarkers based on molecular traces of neural repair and regeneration, which could transform prognostic and predictive modeling of post-TBI recovery trajectories.
Authors: Przemyslaw Swiatkowski; Emily Sewell; Eric S Sweet; Samantha Dickson; Rachel A Swanson; Sara A McEwan; Nicholas Cuccolo; Mark E McDonnell; Mihir V Patel; Nevin Varghese; Barclay Morrison; Allen B Reitz; David F Meaney; Bonnie L Firestein Journal: Neurobiol Dis Date: 2018-07-19 Impact factor: 5.996
Authors: Elizabeth B Hutchinson; Susan C Schwerin; Alexandru V Avram; Sharon L Juliano; Carlo Pierpaoli Journal: J Neurosci Res Date: 2017-06-13 Impact factor: 4.164
Authors: Yu Liu; Samuel S McAfee; Natalie M Guley; Nobel Del Mar; Wei Bu; Scott A Heldt; Marcia G Honig; Bob M Moore; Anton Reiner; Detlef H Heck Journal: eNeuro Date: 2017-08-18