Bilateral transcranial direct‐current stimulation promotes migration of subventricular zone‐derived neuroblasts toward ischemic brain

Ischemic insult stimulates proliferation of neural stem cells (NSCs) in the subventricular zone (SVZ) after stroke. However, only a fraction of NSC‐derived neuroblasts from SVZ migrate toward poststroke brain region. We have previously reported that direct‐current stimulation guides NSC migration toward the cathode in vitro. Accordingly, we set up a new method of transcranial direct‐current stimulation (tDCS), in which the cathodal electrode is placed on the ischemic hemisphere and anodal electrode on the contralateral hemisphere of rats subjected to ischemia–reperfusion injury. We show that the application of this bilateral tDCS (BtDCS) promotes the migration of NSC‐derived neuroblasts from SVZ toward the cathode direction into poststroke striatum. Reversing the position of the electrodes blocks the effect of BtDCS on the migration of neuroblasts from SVZ. BtDCS protects against neuronal death and improves the functional recovery of stroke animals. Thus, the migration of NSC‐derived neuroblasts from SVZ toward poststroke brain region contributes to the effect of BtDCS against ischemia‐induced neuronal death, supporting a potential development of noninvasive BtDCS as an endogenous neurogenesis‐based stroke therapy.

[1]  Young-Jin Jung,et al.  Contralesional Application of Transcranial Direct Current Stimulation on Functional Improvement in Ischemic Stroke Mice , 2020, Stroke.

[2]  G. Fink,et al.  Transcranial Current Stimulation Alters the Expression of Immune-Mediating Genes , 2019, Front. Cell. Neurosci..

[3]  Mai Lu,et al.  A safety study of 500 μA cathodal transcranial direct current stimulation in rat , 2019, BMC Neuroscience.

[4]  Shapour Jaberzadeh,et al.  The Effect of Unihemispheric Concurrent Dual-Site Transcranial Direct Current Stimulation of Primary Motor and Dorsolateral Prefrontal Cortices on Motor Function in Patients With Sub-Acute Stroke , 2018, Front. Hum. Neurosci..

[5]  R. Dijkhuizen,et al.  Noninvasive Brain Stimulation to Enhance Functional Recovery After Stroke: Studies in Animal Models , 2018, Neurorehabilitation and neural repair.

[6]  S. Kautz,et al.  Transcranial Direct Current Stimulation for Poststroke Motor Recovery: Challenges and Opportunities , 2018, PM & R : the journal of injury, function, and rehabilitation.

[7]  Heidi M. Schambra,et al.  Transcranial Direct Current Stimulation Enhances Motor Skill Learning but Not Generalization in Chronic Stroke , 2018, Neurorehabilitation and neural repair.

[8]  F. Nicoletti,et al.  Genetic deletion of mGlu2 metabotropic glutamate receptors improves the short-term outcome of cerebral transient focal ischemia , 2017, Molecular Brain.

[9]  Min Zhao,et al.  Electrical Guidance of Human Stem Cells in the Rat Brain , 2017, Stem cell reports.

[10]  Rong Hu,et al.  A non-ionotropic activity of NMDA receptors contributes to glycine-induced neuroprotection in cerebral ischemia-reperfusion injury , 2017, Scientific Reports.

[11]  S. Kautz,et al.  Safety and tolerability of transcranial direct current stimulation to stroke patients – A phase I current escalation study , 2017, Brain Stimulation.

[12]  Ling Wei,et al.  Neuroprotective and regenerative roles of intranasal Wnt-3a administration after focal ischemic stroke in mice , 2017, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[13]  F. Liu,et al.  Bisperoxovandium (pyridin‐2‐squaramide) targets both PTEN and ERK1/2 to confer neuroprotection , 2017, British journal of pharmacology.

[14]  N. Bolognini,et al.  Safety Review of Transcranial Direct Current Stimulation in Stroke , 2017, Neuromodulation : journal of the International Neuromodulation Society.

[15]  S. Lefebvre,et al.  Anatomical Parameters of tDCS to Modulate the Motor System after Stroke: A Review , 2017, Front. Neurol..

[16]  Rudolf Graf,et al.  Transcranial Direct Current Stimulation Modulates Neurogenesis and Microglia Activation in the Mouse Brain , 2016, Clinical Neurophysiology.

[17]  G. Fink,et al.  Transcranial direct current stimulation accelerates recovery of function, induces neurogenesis and recruits oligodendrocyte precursors in a rat model of stroke , 2016, Experimental Neurology.

[18]  H. Hirase,et al.  Calcium imaging reveals glial involvement in transcranial direct current stimulation-induced plasticity in mouse brain , 2016, Nature Communications.

[19]  Marco Cursi,et al.  Safety and Efficacy of Transcranial Direct Current Stimulation in Acute Experimental Ischemic Stroke , 2013, Stroke.

[20]  Rudolf Graf,et al.  Multi-Session Transcranial Direct Current Stimulation (tDCS) Elicits Inflammatory and Regenerative Processes in the Rat Brain , 2012, PloS one.

[21]  Mitsunori Matsumae,et al.  Electrical Stimulation of the Cerebral Cortex Exerts Antiapoptotic, Angiogenic, and Anti-Inflammatory Effects in Ischemic Stroke Rats Through Phosphoinositide 3-Kinase/Akt Signaling Pathway , 2009, Stroke.

[22]  P. Brundin,et al.  Absence of striatal newborn neurons with mature phenotype following defined striatal and cortical excitotoxic brain injuries , 2009, Experimental Neurology.

[23]  M. Nitsche,et al.  Safety limits of cathodal transcranial direct current stimulation in rats , 2009, Clinical Neurophysiology.

[24]  M. Chopp,et al.  Ischemic stroke and neurogenesis in the subventricular zone , 2008, Neuropharmacology.

[25]  Q. Wan,et al.  Direct‐Current Electrical Field Guides Neuronal Stem/Progenitor Cell Migration , 2008, Stem cells.

[26]  L. Cohen,et al.  Non-invasive brain stimulation: a new strategy to improve neurorehabilitation after stroke? , 2006, The Lancet Neurology.

[27]  M. Nitsche,et al.  Anticonvulsant Effects of Transcranial Direct‐current Stimulation (tDCS) in the Rat Cortical Ramp Model of Focal Epilepsy , 2006, Epilepsia.

[28]  H. Okano,et al.  Subventricular Zone-Derived Neuroblasts Migrate and Differentiate into Mature Neurons in the Post-Stroke Adult Striatum , 2006, The Journal of Neuroscience.

[29]  M. Nitsche,et al.  After-effects of transcranial direct current stimulation (tDCS) on cortical spreading depression , 2006, Neuroscience Letters.

[30]  J. Mocco,et al.  An improved test of neurological dysfunction following transient focal cerebral ischemia in rats , 2006, Journal of Neuroscience Methods.

[31]  A. Walker,et al.  Subventricular Zone Neuroblasts Emigrate Toward Cortical Lesions , 2005, Journal of neuropathology and experimental neurology.

[32]  Sergio P. Rigonatti,et al.  Transcranial direct current stimulation of the unaffected hemisphere in stroke patients , 2005, Neuroreport.

[33]  C. Lundberg,et al.  In vivo labeling of neuroblasts in the subventricular zone of rats , 2005, Journal of Neuroscience Methods.

[34]  F. Gage,et al.  Robust in vivo gene transfer into adult mammalian neural stem cells by lentiviral vectors. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Q. Wan,et al.  Circadian regulation of GABAA receptor function by CKIε-CKIδ in the rat suprachiasmatic nuclei , 2004, Nature Neuroscience.

[36]  Hongjun Song,et al.  Neurogenesis in the adult brain: new strategies for central nervous system diseases. , 2004, Annual review of pharmacology and toxicology.

[37]  M. Nitsche,et al.  Pharmacological Modulation of Cortical Excitability Shifts Induced by Transcranial Direct Current Stimulation in Humans , 2003, The Journal of physiology.

[38]  R. Felling,et al.  Enhanced neurogenesis following stroke , 2003, Journal of neuroscience research.

[39]  Jack M Parent,et al.  Rat forebrain neurogenesis and striatal neuron replacement after focal stroke , 2002, Annals of neurology.

[40]  O. Lindvall,et al.  Neuronal replacement from endogenous precursors in the adult brain after stroke , 2002, Nature Medicine.

[41]  S. Morrison,et al.  Brain Repair by Endogenous Progenitors , 2002, Cell.

[42]  M Chopp,et al.  Proliferation and differentiation of progenitor cells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia , 2001, Neuroscience.

[43]  David A. Greenberg,et al.  Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[44]  M. Chopp,et al.  Therapeutic Benefit of Intravenous Administration of Bone Marrow Stromal Cells After Cerebral Ischemia in Rats , 2001, Stroke.

[45]  D. Petullo,et al.  Model development and behavioral assessment of focal cerebral ischemia in rats. , 1999, Life sciences.

[46]  J. Grotta,et al.  An Alternative Method for the Quantitation of Neuronal Damage after Experimental Middle Cerebral Artery Occlusion in Rats: Analysis of Behavioral Deficit , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[47]  I. Módy,et al.  Regulation of NMDA channel function by endogenous Ca2+-dependent phosphatase , 1994, Nature.