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Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):12913-8. doi: 10.1073/pnas.1404109111. Epub 2014 Aug 18.

Optogenetic neuronal stimulation promotes functional recovery after stroke.

Author information

  • 1Departments of Neurosurgery, Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA 94305 gsteinberg@stanford.edu mycheng@stanford.edu.
  • 2Departments of Neurosurgery, Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA 94305.
  • 3Departments of Neurosurgery, Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA 94305 Bioengineering, and.
  • 4Psychiatry and Behavioral Sciences.
  • 5Bioengineering, and Neuroscience PhD Program.
  • 6Bioengineering, and Psychiatry and Behavioral Sciences, Cracking the Neural Code (CNC) Program, Howard Hughes Medical Institute, and.

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.

KEYWORDS:

channelrhodopsin; stroke recovery

PMID:
25136109
[PubMed - indexed for MEDLINE]
PMCID:
PMC4156770
Free PMC Article
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