title: Optogenetic neuronal stimulation promotes functional recovery after stroke.
abstract: Clinical and research efforts have focused on promoting functional recovery after stroke. Brain stimulation strategies are particularly promising because they allow direct manipulation of the target area's excitability. However, elucidating the cell type and mechanisms mediating recovery has been difficult because existing stimulation techniques nonspecifically target all cell types near the stimulated site. To circumvent these barriers, we used optogenetics to selectively activate neurons that express channelrhodopsin 2 and demonstrated that selective neuronal stimulations in the ipsilesional primary motor cortex (iM1) can promote functional recovery. Stroke mice that received repeated neuronal stimulations exhibited significant improvement in cerebral blood flow and the neurovascular coupling response, as well as increased expression of activity-dependent neurotrophins in the contralesional cortex, including brain-derived neurotrophic factor, nerve growth factor, and neurotrophin 3. Western analysis also indicated that stimulated mice exhibited a significant increase in the expression of a plasticity marker growth-associated protein 43. Moreover, iM1 neuronal stimulations promoted functional recovery, as stimulated stroke mice showed faster weight gain and performed significantly better in sensory-motor behavior tests. Interestingly, stimulations in normal nonstroke mice did not alter motor behavior or neurotrophin expression, suggesting that the prorecovery effect of selective neuronal stimulations is dependent on the poststroke environment. These results demonstrate that stimulation of neurons in the stroke hemisphere is sufficient to promote recovery.
authors.affiliation: Departments of Neurosurgery, Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA 94305 gsteinberg@stanford.edu mycheng@stanford.edu.
authors.forename: Michelle Y
authors.initials: MY
authors.lastname: Cheng
authors.affiliation: Departments of Neurosurgery, Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Eric H
authors.initials: EH
authors.lastname: Wang
authors.affiliation: Departments of Neurosurgery, Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA 94305 Bioengineering, and.
authors.forename: Wyatt J
authors.initials: WJ
authors.lastname: Woodson
authors.affiliation: Departments of Neurosurgery, Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wang
authors.affiliation: Departments of Neurosurgery, Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Guohua
authors.initials: G
authors.lastname: Sun
authors.affiliation: Psychiatry and Behavioral Sciences.
authors.forename: Alex G
authors.initials: AG
authors.lastname: Lee
authors.affiliation: Departments of Neurosurgery, Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Arac
authors.affiliation: Bioengineering, and Neuroscience PhD Program.
authors.forename: Lief E
authors.initials: LE
authors.lastname: Fenno
authors.affiliation: Bioengineering, and Psychiatry and Behavioral Sciences, Cracking the Neural Code (CNC) Program, Howard Hughes Medical Institute, and.
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
authors.affiliation: Departments of Neurosurgery, Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA 94305 gsteinberg@stanford.edu mycheng@stanford.edu.
authors.forename: Gary K
authors.initials: GK
authors.lastname: Steinberg
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001522:Behavior, Animal / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology / Q000528:radiation effects; D000075402:Channelrhodopsins; D003342:Corpus Striatum / Q000502:physiology / Q000528:radiation effects; D004195:Disease Models, Animal; D019922:GAP-43 Protein / Q000235:genetics; D025602:Halorhodopsins / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology* / Q000628:therapy*; D053685:Laser Therapy / Q000379:methods*; D008027:Light; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009044:Motor Cortex / Q000503:physiopathology / Q000528:radiation effects; D020932:Nerve Growth Factor / Q000235:genetics; D009473:Neuronal Plasticity / Q000502:physiology / Q000528:radiation effects; D055100:Optical Fibers; D010775:Photic Stimulation / Q000379:methods*; D020127:Recovery of Function / Q000502:physiology* / Q000528:radiation effects; D013003:Somatosensory Cortex / Q000502:physiology / Q000528:radiation effects
chemical_list: D001426:Bacterial Proteins; D000075402:Channelrhodopsins; D019922:GAP-43 Protein; D025602:Halorhodopsins; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria; D020932:Nerve Growth Factor
keywords: channelrhodopsin; stroke recovery