title: Safety and efficacy of transcranial direct current stimulation in acute experimental ischemic stroke.
abstract: OBJECTIVE
  Transcranial direct current stimulation is emerging as a promising tool for the treatment of several neurological conditions, including cerebral ischemia. The therapeutic role of this noninvasive treatment is, however, limited to chronic phases of stroke. We thus ought to investigate whether different stimulation protocols could also be beneficial in the acute phase of experimental brain ischemia.
  
  
  METHODS
  The influence of both cathodal and anodal transcranial direct current stimulation in modifying brain metabolism of healthy mice was first tested by nuclear magnetic resonance spectroscopy. Then, mice undergoing transient proximal middle cerebral artery occlusion were randomized and treated acutely with anodal, cathodal, or sham transcranial direct current stimulation. Brain metabolism, functional outcomes, and ischemic lesion volume, as well as the inflammatory reaction and blood brain barrier functionality, were analyzed.
  
  
  RESULTS
  Cathodal stimulation was able, if applied in the acute phase of stroke, to preserve cortical neurons from the ischemic damage, to reduce inflammation, and to promote a better clinical recovery compared with sham and anodal treatments. This finding was attributable to the significant decrease of cortical glutamate, as indicated by nuclear magnetic resonance spectroscopy. Conversely, anodal stimulation induced an increase in the postischemic lesion volume and augmented blood brain barrier derangement.
  
  
  CONCLUSIONS
  Our data indicate that transcranial direct current stimulation exerts a measurable neuroprotective effect in the acute phase of stroke. However, its timing and polarity should be carefully identified on the base of the pathophysiological context to avoid potential harmful side effects.
authors: From the Neuroimmunology Unit (L.P.-J., M.B., M.G., S.S., G.C., G.M.) and Experimental Neurophysiology Unit, Division of Neuroscience, Institute of Experimental Neurology (INSPE), DIBIT-II, San Raffaele Scientific Institute (M.C., M.C., L.T., G.C., L.L.), Vita-Salute San Raffaele University, Milan, Italy; and Dulbecco Telethon Institute, Biomolecular NMR Laboratory c/o Center for Translational Genomics and Bioinformatics, Ospedale San Raffaele, Milan, Italy (E.G., S.M., G.M.).
authors: Luca
authors: L
authors: Peruzzotti-Jametti
authors: Marco
authors: M
authors: Cambiaghi
authors: Marco
authors: M
authors: Bacigaluppi
authors: Mattia
authors: M
authors: Gallizioli
authors: Edoardo
authors: E
authors: Gaude
authors: Silvia
authors: S
authors: Mari
authors: Stefano
authors: S
authors: Sandrone
authors: Marco
authors: M
authors: Cursi
authors: Luis
authors: L
authors: Teneud
authors: Giancarlo
authors: G
authors: Comi
authors: Giovanna
authors: G
authors: Musco
authors: Gianvito
authors: G
authors: Martino
authors: Letizia
authors: L
authors: Leocani
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000503:physiopathology* / Q000628:therapy*; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods*; D004599:Electric Stimulation Therapy / Q000379:methods*; D004566:Electrodes; D018698:Glutamic Acid / Q000378:metabolism; D007249:Inflammation; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020521:Stroke / Q000503:physiopathology* / Q000628:therapy*
chemical_list: D018698:Glutamic Acid
keywords: electric stimulation; mice; neuroprotective agents; stroke