Acute seizure suppression by transcranial direct current stimulation in rats.
OBJECTIVE
Cathodal transcranial direct current stimulation (tDCS) is a focal neuromodulation technique that suppresses cortical excitability by low-amplitude constant electrical current, and may have an antiepileptic effect. Yet, tDCS has not been tested in status epilepticus (SE). Furthermore, a combined tDCS and pharmacotherapy antiseizure approach is unexplored. We therefore examined in the rat pentylenetetrazol (PTZ) SE model whether cathodal tDCS (1) suppresses seizures, (2) augments lorazepam (LZP) efficacy, and (3) enhances GABAergic cortical inhibition.


METHODS
Experiment 1 aimed to identify an effective cathodal tDCS intensity. Rats received intraperitoneal PTZ followed by tDCS (sham, cathodal 1 mA, or cathodal 0.1 mA; for 20 min), and then a second PTZ challenge. In Experiment 2, two additional animal groups received a subtherapeutic LZP dose after PTZ, and then verum or sham tDCS. Clinical and electroencephalography (EEG) epileptic activity were compared between all groups. In Experiment 3, we measured GABA-mediated paired-pulse inhibition of the motor evoked potential by paired-pulse transcranial magnetic stimulation (ppTMS) in rats that received PTZ or saline, and either verum or sham tDCS.


RESULTS
Cathodal 1 mA tDCS (1) reduced EEG spike bursts, and suppressed clinical seizures after the second PTZ challenge, (2) in combination with LZP was more effective in seizure suppression and improved the clinical seizure outcomes compared to either tDCS or LZP alone, and (3) prevented the loss of ppTMS motor cortex inhibition that accompanied PTZ injection.


CONCLUSIONS
These results suggest that cathodal 1 mA tDCS alone and in combination with LZP can suppress seizures by augmenting GABAergic cortical inhibition.
Neuromodulation Program, Division of Epilepsy and Clinical Neurophysiology, and the F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School Boston, Massachusetts, USA.
Sameer C
SC
Dhamne
Department of Neurology, The Agnes Ginges Center of Human Neurogenetics, Hadassah-Hebrew University Medical Center Jerusalem, Israel.
Dana
D
Ekstein
Neuromodulation Program, Division of Epilepsy and Clinical Neurophysiology, and the F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School Boston, Massachusetts, USA ; Department of Pediatric Neurology, The First Affiliated Hospital of Zhengzhou University Zhengzhou, China.
Zhihong
Z
Zhuo
Neuromodulation Program, Division of Epilepsy and Clinical Neurophysiology, and the F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School Boston, Massachusetts, USA.
Roman
R
Gersner
Department of Anesthesia, Boston Children's Hospital, Harvard Medical School Boston, Massachusetts, USA.
David
D
Zurakowski
Neuromodulation Program, Division of Epilepsy and Clinical Neurophysiology, and the F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School Boston, Massachusetts, USA.
Tobias
T
Loddenkemper
Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School Boston, Massachusetts, USA.
Alvaro
A
Pascual-Leone
Department of Neurology, Perelman School of Medicine, University of Pennsylvania Health System Philadelphia, Pennsylvania, USA.
Frances E
FE
Jensen
Neuromodulation Program, Division of Epilepsy and Clinical Neurophysiology, and the F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School Boston, Massachusetts, USA ; Department of Pediatric Neurology, The First Affiliated Hospital of Zhengzhou University Zhengzhou, China ; Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School Boston, Massachusetts, USA.
Alexander
A
Rotenberg