Behavioural Brain Research 217 (2011) 99–103 Contents lists available at ScienceDirect Behavioural Brain Research journal homepage: www.elsevier.com/locate/bbr Research report Transcranial direct current stimulation decreases convulsions and spatial memory deficits following pilocarpine-induced status epilepticus in immature rats Tohru Kamida a,∗ , Shiqi Kong b , Nobuoki Eshima c , Tatsuya Abe a , Minoru Fujiki a , Hidenori Kobayashi a a Department of Neurosurgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593, Japan b Department of Neurosurgery, XingTai People Hospital, HeiBei Province, China c Department of Biostatistics, Oita University Faculty of Medicine, Oita, Japan article info Article history: Received 26 March 2010 Received in revised form 28 August 2010 Accepted 30 August 2010 Available online 6 September 2010 Keywords: Transcranial direct current stimulation (tDCS) Status epilepticus Immature rat Neuroprotective effect Cognitive performance abstract Purpose: Transcranial direct current stimulation (tDCS) is a recently available, noninvasive brain stimu- lation technique. The effects of cathodal tDCS on convulsions and spatial memory after status epilepticus (SE) in immature animals were investigated. Methods: Rats underwent lithium–pilocarpine-induced SE at postnatal day (P) 20–21 and received daily 30-min cathodal tDCS for 2 weeks at P23-36 through a unilateral epicranial electrode at 200 A. After tDCS, convulsions over 2 weeks were estimated by 20-h/day video monitoring. The rats were tested in a water maze for spatial learning at P50-53 and the brains were examined for cell loss and mossy fiber sprouting. Results: Long-term treatment with weak cathodal tDCS reduced SE-induced hippocampal cell loss, supra- granular and CA3 mossy fiber sprouting, and convulsions (reduction of 21%) in immature rats. The tDCS treatment also rescued cognitive impairment following SE. Conclusions: These findings suggested that cathodal tDCS has neuroprotective effects on the immature rat hippocampus after pilocarpine-induced SE, including reduced sprouting and subsequent improvements in cognitive performance. Such treatment might also have an antiepileptic effect. Crown Copyright © 2010 Published by Elsevier B.V. All rights reserved. 1. Introduction Status epilepticus (SE) is a common condition in emer- gency pediatric patients, characterized by repetitive or prolonged seizures. Previous studies suggested that SE in the immature brain is less detrimental than SE in adults [29]. However, some reports indicate that SE in the immature brain induces neuronal loss and aberrant growth of granule cell axons or mossy fibers within the hippocampus, and also results in cognitive impairment and devel- opment of epilepsy [7,8,16,19,28,31]. It is essential to identify a treatment for these patients that relieves the immature brain from such insults. Since a report by Bindman et al. [3], several authors have studied transcranial direct current stimulation (tDCS) as a nonin- vasive stimulation technique in human [4,10,11,15,23–25]. Weak direct currents delivered through the scalp induce alterations in cortical excitability, which last even after stimulation has ceased [2,4,10,11,15,22,23,25]. Anodal tDCS enhances [4,10,15,22–25] and ∗ Corresponding author. Tel.: +81 97 586 5862; fax: +81 97 586 5869. E-mail address: kamida@med.oita-u.ac.jp (T. Kamida). cathodal tDCS reduces [2,4,10,11,18,23,25] cortical excitability. Previous studies also suggested that cathodal tDCS decreases cortical excitability in the epileptogenic focus on the surface of the brain, although little is known about the mechanisms underlying the antiepileptic effects [12,18,23]. However, the effects of cathodal tDCS on seizure-induced structural and behav- ioral alterations and on cognitive impairment remain unknown. Lithium–pilocarpine (Li–PC) induces SE and seizure-related brain injury in animals following systemic administration, leading to spontaneous recurrent seizures (SRS) and long-term cognitive impairment [5,7–9,16,20,26,30]. The present study investigated the effects of cathodal tDCS on neuronal loss and mossy fiber sprouting within the hippocampus of immature rats after Li–PC-induced SE, as well as on convulsions and spatial memory. 2. Materials and methods Fig. 1 provides an overview and timeline for the procedures used in this study. 2.1. Animals Eighteen male Wistar rats (Kyudo Co, Kumamoto, Japan) were used during this study, in accordance with the guidelines of the Oita University Animal Care Com- 0166-4328/$ – see front matter. Crown Copyright © 2010 Published by Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2010.08.050