TrkB Partial Activation Reduces Epileptogenesis After Traumatic Brain Injury
Abstract number :
3.014
Submission category :
1. Translational Research: 1A. Mechanisms / 1A1. Epileptogenesis of acquired epilepsies
Year :
2016
Submission ID :
196966
Source :
www.aesnet.org
Presentation date :
12/5/2016 12:00:00 AM
Published date :
Nov 21, 2016, 18:00 PM
Authors :
Feng Gu, Stanford University, Stanford, California; Tao Yang, Stanford University; Frank Longo, Stanford University; and David Prince, Stanford University
Rationale: Post-traumatic epilepsy is one of the most common forms of acquired epilepsy worldwide. Currently, there is no effective way to prevent the epileptogenesis following traumatic brain injury (TBI). It is known that decreased GABAergic inhibition due to abnormalities of interneurons plays a critical role in epileptogenesis following TBI. To prevent post-traumatic epileptogenesis (PTE), it is important to develop a way to improve the function of interneurons in the injured brain. Our previous results showed that chronic TrkB activation can rescue the interneuronal deficits and increase GABAergic inhibition after cortical injury. This study focused on whether this improvement in interneuronal function can translate into reduced PTE. Methods: To test our hypothesis, we used the partial neocortical isolation (undercut or UC) model of PTE in SD rats that were treated intraperitoneally for 1-2 weeks beginning the day of injury with LM22A-4 or PTX BD4-3, small molecule partial agonists at the BDNF TrkB receptor. In vitro extracellular field potential recording from cortical slices and in vivo video-EEG recording of pentylenetetrazol (PTZ)-induced seizures were performed to examine the effect of chronic trkB activation on PTE. Results: Our results reveal that 1) UC animals are more likely to develop seizures either in in vitro slices or in vivo; 2) trkB activation significantly decreases the incidence of spontaneous epileptiform bursts, as well as those evoked by electrical stimulation or by perfusion of slices from UC cortex with ACSF containing a low concentration of bicuculline; 3) the incidence of PTZ-induced seizures is decreased from 73% in UC animals treated with saline (n=26) to 40% in UC animals treated with BD4-3 (n=25). Conclusions: These results indicate that chronic TrkB activation by a partial agonist after cortical injury can reduce PTE by improving GABAergic interneuronal function and may potentially serve as an effective therapeutic option for prophylactic treatment of post-traumatic epilepsy. Funding: Supported by grant NS082644 from the NINDS (DP).
Translational Research