Journal article

Acute treatment with TrkB agonist LM22A-4 confers neuroprotection and preserves myelin integrity in a mouse model of pediatric traumatic brain injury

Jessica L Fletcher, Larissa K Dill, Rhiannon J Wood, Sharon Wang, Kate Robertson, Simon S Murray, Akram Zamani, Bridgette D Semple



Young children have a high risk of sustaining a traumatic brain injury (TBI), which can have debilitating life-long consequences. Importantly, the young brain shows particular vulnerability to injury, likely attributed to ongoing maturation of the myelinating nervous system at the time of insult. Here, we examined the effect of acute treatment with the partial tropomyosin receptor kinase B (TrkB) agonist, LM22A-4, on pathological and neurobehavioral outcomes after pediatric TBI, with the hypothesis that targeting TrkB would minimize tissue damage and support functional recovery. We focused on myelinated tracts-the corpus callosum and external capsules-based on recent evidence that TrkB activ..

View full abstract


Funding Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia (NHMRC) via a Career Development Fellowship and Project Grant to BDS, as well as project funding from the Department of Anatomy and Neuroscience, The University of Melbourne, to JF and BDS. JF was supported by a 2018 Melbourne Neuroscience Institute Fellowship. The authors also thank Dr. David Gonsalvez (School of Biomedical Sciences, Monash University) for assistance with SCoRe imaging, as well as the Monash Histology Platform and Monash Micro Imaging Platform at the Alfred Research Alliance and the Biological Optical Microscopy Platform (BOMP) at the University of Melbourne for their facilities and technical support.