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Behavior

Repetitive Transcranial Magnetic Stimulation to the Unilateral Hemisphere of Rat Brain

Published: October 22nd, 2016

DOI:

10.3791/54217

1Department of Rehabilitation Medicine, Chungnam National University Hospital, Daejeon, 2Department of Biomedical Engineering, Seoul National University College of Medicine, 3Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University, 4Department of Biomedical Engineering, Seoul National University Hospital, 5Department of Nuclear Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 6Department of Rehabilitation Medicine, Gangwon Do Rehabilitation Hospital, 7Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul National University College of Medicine

We applied repetitive transcranial magnetic stimulation (rTMS) to the unilateral hemisphere of rat brain, by placing a 25-mm figure-8 coil 1 cm lateral to the vertex on the biauricular line and angulating the coil by 45°. An in-house water cooling system was used for rTMS for more than 20 min.

Previous rodent models of repetitive transcranial magnetic stimulation (rTMS) adopted whole-brain stimulation instead of unilateral hemispheric rTMS, which is unlike the protocols used for human subjects. We report a successful application of rTMS to the unilateral hemisphere of rat brain. The rTMS was delivered with a low-frequency (1 Hz), high-frequency (20 Hz), or sham stimulation protocol to one side of the brain by using a small 25-mm figure-8 coil. We placed the center of the coil 1 cm lateral to the vertex on the biauricular line and angulated the coil 45° to the ground to minimize a potential direct effect of rTMS on the contralateral cortex. We also used an in-house water cooling system to enable repetitive magnetic stimulation for more than 20 min, even at a 20-Hz stimulation frequency. Increases in the transcriptions of immediate early genes (Arc, Junb, and Egr2) were greater after rTMS than after sham stimulation. After 5 consecutive days of 20-min 1-Hz rTMS, bdnf mRNA expression was significantly higher in stimulated cortex than in contralateral side. The model presented herein will elucidate the molecular mechanisms of rTMS by allowing analysis of the inter-hemispheric difference in its effect.

Repetitive transcranial magnetic stimulation (rTMS), a tool for non-invasive brain stimulation and neuromodulation, has been applied in the treatment of various conditions such as central pain1,2, depression3, migraine4, and even stroke5-7. Rapidly changing electrical current through coils on the head induces an electrical field on the cerebral cortex and a resultant neuronal activation. The excitability of the cerebral cortex can be modulated by rTMS, which can last for more than 30 min after the stimulation is terminated.

Suggested mechanisms of the rTMS after-effect include long-term potentiati....

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All of the procedures using animals were reviewed and approved by the Institutional Animal Care and Use Committee of Seoul National University Hospital.

1. Experimental Setup

  1. Animal preparation
    1. Allow male Sprague-Dawley rats 1 week to adapt to their new environment before starting the experiment.
      NOTE: Although 8-week old rats were used in the present study, a developing or adult brain can be chosen according to the research hypotheses.
  2. Inhalation anesthesia .......

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Fifteen 8-week old male Sprague-Dawley rats were used for a separate inter-rater reliability analysis of MT determination. Using palpation of muscle twitching, the MTs were obtainable in all rats and measured as 33.00 ± 4.21% maximal stimulator output (% MSO) and 33.93 ± 0.88% MSO, respectively, by two independent researchers. Bland-Altman bias was -0.93, and the 95% limits of agreement were -9.13 to 7.26%.

In the micr.......

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The primary purpose of this study was to introduce an animal model of unilateral rTMS. Although unilateral stimulation is one of the most fundamental characteristics of human rTMS research, many studies have not adopted it in small animals. However, Rotenberg et al.15 recorded contralateral MEPs with stimulation of 100% MT using a figure-8 coil with an outside lobe diameter of 20 mm, whereas stimulation with 112.5% and 133.3% MT produced ipsilateral as well as contralateral MEPs. This might be because.......

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This work was supported by the Korea Research Foundation Grant funded by the Korean Government (KRF-2008-313-E00458). The authors thank Jin-Joo Lee for the technical assistance.

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Name Company Catalog Number Comments
Homeothermic blanket with a rectal probe Harvard apparatus 507222F
Isoflurane (Forane sol.) Choongwae
Propofol (Provive Inj. 1% 20ml) Claris Lifesciences
Repetitive magnetic stimulator (Magstim Rapid2) Magstim Company Ltd
25 mm figure-of-8 coil Magstim Company Ltd 1165-00
PET-CT GE Healthcare
QIAzol Lysis Reagent Qiagen (US Patent No. 5,346,994)
RNeasy Lipid Tissue Mini Kit Qiagen 74804
RNeasy Mini Spin Columns Qiagen (Mat No. 1011708)
Agilent 2100 Bioanalyzer Agilent Technologies
Ambion Illumina RNA amplification kit Ambion
Nanodrop Spectrophotometer NanoDrop ND-1000
Illumina RatRef-12 Expression BeadChip Illumina, Inc.
Amersham fluorolink streptavidin-Cy3 GE Healthcare Bio-Sciences

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