Transcranial direct current stimulation (tDCS) affects neuroinflammation parameters and behavioral seizure activity in pentylenetetrazole-induced kindling in rats

Abstract

Despite the introduction of new antiepileptic drugs, about 30 % of patients with epilepsy are refractory to drug therapy. Thus, the search for non-pharmacological interventions such as transcranial direct current stimulation (tDCS) may be an alternative, either alone or in combination with low doses of anticonvulsants. This study evaluated the effect of anodal (a-tDCS) and cathodal tDCS (c-tDCS) on seizure behavior and neuroinflammation parameters. Rats were submitted to the kindling model induced by pentylenetetrazole (PTZ) using diazepam (DZP) as anticonvulsant standard. tDCS groups were submitted to 10 sessions of a-tDCS or c-tDCS or SHAM-tDCS. Every 3 days they received saline (SAL), low dose of DZP (alone or in combination with tDCS) or effective dose of DZP 30 min before administration of PTZ, totaling 16 days of protocol. Neither a-tDCS nor c-tDCS reduced the occurrence of clonic forelimb seizures (convulsive motor seizures – stage 3 by the adapted Racine scale we based on). Associated with DZP, c-tDCS (c-tDCS/DZP0.15) increased the latency to first clonic forelimb seizure on the 10th and 16th days. Hippocampal IL-1β levels were reduced by c-tDCS and c-tDCS/DZP0.15. In contrast, these treatments induced an increase in cortical IL-1β levels. Hippocampal TNF-α levels were not altered by c-tDCS or a-tDCS, but c-tDCS and c-tDCS/DZP0.15 increased those levels in cerebral cortex. Cortical NGF levels were increased by c-tDCS and c-tDCS/DZP0.15. a-tDCS/DZP0.15 reduced hippocampal BDNF levels and c-tDCS/DZP0.15 increased these levels in cerebral cortex. In conclusion, c-tDCS alone or in combination with a low dose of DZP showed to affect neuroinflammation, improving central neurotrophin levels and decreasing hippocampal IL-1β levels after PTZ-induced kindling without statistically significant effect on seizure behavior.