title: Safety aspects of chronic low-frequency transcranial magnetic stimulation based on localized proton magnetic resonance spectroscopy and histology of the rat brain.
abstract: Because repetitive transcranial magnetic stimulation (rTMS) is capable of inducing lasting alterations of cortical excitability, it represents a promising therapeutic tool in several neuropsychiatric disorders. However, rTMS, especially when applied chronically, may cause harmful effects in the stimulated tissue. To study the safety of chronic rTMS we used a novel small stimulation coil, which was specially designed to treat rats, and investigated brain tissue using in vivo localized proton magnetic resonance spectroscopy (MRS) and post mortem histological analysis. Histology was based on a modified stereology method in combination with immunohistochemistry applying antibodies against OX-6, OX-42, ED, and GFAP to detect any microglial and/or astrocytic activation 48 h after the last TMS session. Conscious rats were treated with a daily suprathreshold rTMS regimen of 1000 stimuli applied on 5 consecutive days at a frequency of 1 Hz. In comparison with control animals receiving magnetic stimulation over the lumbar spine, quantitative evaluations of cerebral metabolite concentrations by proton MRS revealed no significant alterations of N-acetyl-aspartate, creatine and phosphocreatine, choline-containing compounds, myo-inositol, glucose and lactate after chronic rTMS. Similarly to the in vivo results, post mortem histology revealed no changes in microglial and astrocytic activation after rTMS. In conclusion, these data provide support for the safety of chronic rTMS. However, they do not exclude acute changes on neurotransmitters systems or other physiologic responses during or directly after the rTMS treatment.
authors.affiliation: Georg-August-Universität Göttingen, Abteilung Klinische Neurophysiologie, 37075, Göttingen, Germany. dliebet@gwdg.de
authors.forename: David
authors.initials: D
authors.lastname: Liebetanz
authors.forename: Susanne
authors.initials: S
authors.lastname: Fauser
authors.forename: Thomas
authors.initials: T
authors.lastname: Michaelis
authors.forename: Boldizsár
authors.initials: B
authors.lastname: Czéh
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Walter
authors.initials: W
authors.lastname: Paulus
authors.forename: Jens
authors.initials: J
authors.lastname: Frahm
authors.forename: Eberhard
authors.initials: E
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D001253:Astrocytes / Q000378:metabolism*; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002452:Cell Count; D053331:Ectodysplasins; D004558:Electric Stimulation / Q000009:adverse effects; D004574:Electromagnetic Fields / Q000009:adverse effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D008161:Lumbosacral Region; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C079432:Bsg protein, rat; D053331:Ectodysplasins; D005904:Glial Fibrillary Acidic Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D051926:Basigin