| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Cheng, Michelle Y. Fenno, Lief E. Wang, Eric H. Woodson, Wyatt J. Arac, Ahmet Sun, Guohua Deisseroth, Karl Lee, Alex G. Steinberg, Gary K. Wang, Stephanie |
| Description |
Author Affiliation: Cheng MY ( Departments of Neurosurgery, Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA 94305 gsteinberg@stanford.edu mycheng@stanford.edu.); Wang EH ( Departments of Neurosurgery, Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA 94305.); Woodson WJ ( Departments of Neurosurgery, Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA 94305 Bioengineering, and.); Wang S ( Departments of Neurosurgery, Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA 94305.); Sun G ( Departments of Neurosurgery, Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA 94305.); Lee AG ( Psychiatry and Behavioral Sciences.); Arac A ( Departments of Neurosurgery, Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA 94305.); Fenno LE ( Bioengineering, and Neuroscience PhD Program.); Deisseroth K ( Bioengineering, and Psychiatry and Behavioral Sciences, Cracking the Neural Code (CNC) Program, Howard Hughes Medical Institute, and.); Steinberg GK ( Departments of Neurosurgery, Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA 94305 gsteinberg@stanford.edu mycheng@stanford.edu.); |
| 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. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
35 |
| Volume Number |
111 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2014-09-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Infarction, Middle Cerebral Artery Physiopathology Therapy Laser Therapy Photic Stimulation Recovery Of Function Physiology Animals Bacterial Proteins Genetics Behavior, Animal Cerebrovascular Circulation Radiation Effects Corpus Striatum Disease Models, Animal GAP-43 Protein Halorhodopsins Luminescent Proteins Mice Mice, Transgenic Motor Cortex Nerve Growth Factor Neuronal Plasticity Optical Fibers Rhodopsin Somatosensory Cortex Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
