TrkB-enhancer Facilitates Functional Recovery After Traumatic Brain Injury

Authors

John Marshall, Brown University
Joanna Szmydynger-Chodobska, Brown University
Mengia S. Rioult-Pedotti, Brown University
Kara Lau, Brown University
Andrea T. Chin, Brown University
Siva K. Reddy Kotla, Chapman University
Rakesh Tiwari, Chapman UniversityFollow
Keykavous Parang, Chapman UniversityFollow
Steven W. Threlkeld, Regis College
Adam Chodobski, Brown University

Document Type

Article

Publication Date

9-8-2017

Abstract

Brain-derived neurotrophic factor (BDNF), a key player in regulating synaptic strength and learning, is dysregulated following traumatic brain injury (TBI), suggesting that stimulation of BDNF signaling pathways may facilitate functional recovery. This study investigates whether CN2097, a peptidomimetic ligand which targets the synaptic scaffold protein, postsynaptic density protein 95, to enhance downstream signaling of tropomyosin-related kinase B, a receptor for BDNF, can improve neurological function after TBI. Moderate to severe TBI elicits neuroinflammation and c-Jun-N-terminal kinase (JNK) activation, which is associated with memory deficits. Here we demonstrate that CN2097 significantly reduces the post-traumatic synthesis of proinflammatory mediators and inhibits the posttraumatic activation of JNK in a rodent model of TBI. The recordings of field excitatory post-synaptic potentials in the hippocampal CA1 subfield demonstrate that TBI inhibits the expression of long-term potentiation (LTP) evoked by high-frequency stimulation of Schaffer collaterals, and that CN2097 attenuates this LTP impairment. Lastly, we demonstrate that CN2097 significantly improves the complex auditory processing deficits, which are impaired after injury. The multifunctionality of CN2097 strongly suggests that CN2097 could be highly efficacious in targeting complex secondary injury processes resulting from neurotrauma.

Comments

This article was originally published in Scientific Reports, volume 7, in 2017. DOI: 10.1038/s41598-017-11316-8

Recommended Citation

Marshall J, Szmydynger-Chodobska J, Rioult-Pedotti MS, et al. TrkB-enhancer facilitates functional recovery after traumatic brain injury. Sci Rep. 2017;7:10995. doi:10.1038/s41598-017-11316-8.

Copyright

The authors

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.