Open AccessAcute seizure suppression by transcranial direct current stimulation in rats
Author(s) -
Dhamne Sameer C.,
Ekstein Dana,
Zhuo Zhihong,
Gersner Roman,
Zurakowski David,
Loddenkemper Tobias,
PascualLeone Alvaro,
Jensen Frances E.,
Rotenberg Alexander
Publication year - 2015
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.226
Subject(s) - transcranial direct current stimulation , medicine , neuromodulation , pentylenetetrazol , epilepsy , transcranial magnetic stimulation , gabaergic , stimulation , lorazepam , anesthesia , electroencephalography , diazepam , motor cortex , neuroscience , status epilepticus , benzodiazepine , psychology , anticonvulsant , psychiatry , inhibitory postsynaptic potential , receptor
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 GABA ergic 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 (pp TMS ) 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 pp TMS motor cortex inhibition that accompanied PTZ injection. Interpretation These results suggest that cathodal 1 mA tDCS alone and in combination with LZP can suppress seizures by augmenting GABA ergic cortical inhibition.