Photolysis of RuBi-GABA with Visible Light for Control of Focal Neocortical Epilepsy in Rats
Abstract number :
3.047
Submission category :
1. Translational Research: 1A. Mechanisms / 1A4. Mechanisms of Therapeutic Interventions
Year :
2016
Submission ID :
198049
Source :
www.aesnet.org
Presentation date :
12/5/2016 12:00:00 AM
Published date :
Nov 21, 2016, 18:00 PM
Authors :
Xiaofeng Yang, Xuanwu Hospital, Capital Medical University, Beijing, China. Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing, China., Minneapolis, Minnesota; Dan Wang, Xuanwu Hospital, Capital Medical University, Beijing, China. Center o
Rationale: Our previous experimental results have demonstrated that the use of blue light generated by a small, light-emitting diode (LED) to uncage RuBi-GABA can rapidly terminate paroxysmal seizure activity in vitro and in vivo. In this study, we used a laser and implantable optical fiber to cause photolysis of RuBi-GABA, to explore the optimal RuBi-GABA concentration for the termination of seizures. Methods: Focal neocortical seizures of anesthetized rats were induced by microinjection of 4-aminopyridine (4-AP) into the motor cortex. Blue light was generated by a laser generator and illumination was delivered via an implantable optical fiber. We examined the effect of RuBi-GABA photolysis (15mV, 30 Sceonds) on the frequency and duration of ictal activity in the presence and absence of RuBi-GABA. At the same time, we also observed the effects of different concentrations of RuBi-GABA on seizure activity. Results: The average duration of seizures and interictal time in the presence of 0.2 mM RuBi-GABA without illumination and absence of RuBi-GABA with blue light illumination only were unchanged compared with the control group (seizure duration: 8038s, 8246s, vs 8047s, p>0.05, and interictal time: 229210s, 274319s, vs 367322s, P>0.05). With the concentration of 0.1mM RuBi-GABA, seizure duration was not significantly reduced by blue light illumination (7444s vs 8047s, P>0.05), but it was significantly increased in the interictal period (924713s vs 367322s, P < 0.05). When the concentration of RuBi-GABA was increased to 0.2mM, the duration of seizures was significantly reduced (128s vs 8047s, p < 0.05) and interictal period was obviously extended (695420s vs 367322s, P < 0.05) by blue light illumination. Conclusions: These results demonstrate that laser photolysis of RuBi-GABA by an implantable optical fiber not only can terminate the seizures but also have a role in the prevention of seizures on rat focal neocortical seizures model. The effect of RuBi-GABA photolysis on controlling seizures activity is concentration dependent. Funding: National Science Foundation (81471391), Beijing Institute for Brain Disorders Foundation (BIBDPXM2014_014226_000016) .
Translational Research