Optogenetic neuronal stimulation promotes functional recovery after stroke

被引：188

作者：

Cheng, Michelle Y. ^{[1
,7
]}

Wang, Eric H. ^{[1
,7
]}

Woodson, Wyatt J. ^{[1
,2
,7
]}

Wang, Stephanie ^{[1
,7
]}

Sun, Guohua ^{[1
,7
]}

Lee, Alex G. ^{[3
]}

Arac, Ahmet ^{[1
,7
]}

Fenno, Lief E. ^{[2
,4
]}

Deisseroth, Karl ^{[2
,3
,5
,6
]}

Steinberg, Gary K. ^{[1
,7
]}

机构：

[1] Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Dept Bioengn, Stanford, CA 94305 USA

[3] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA

[4] Stanford Univ, Sch Med, Neurosci PhD Program, Stanford, CA 94305 USA

[5] Stanford Univ, Sch Med, Cracking Neural Code CNC Program, Stanford, CA 94305 USA

[6] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA

[7] Stanford Univ, Sch Med, Stanford Stroke Ctr, Stanford, CA 94305 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2014年 / 111卷 / 35期

基金：

美国国家卫生研究院;

关键词：

stroke recovery; channelrhodopsin; MOTOR FUNCTION; SOMATOSENSORY CORTEX; NEUROTROPHIC FACTORS; CORTICAL PLASTICITY; BRAIN-STIMULATION; GENE-THERAPY; MICE; ACTIVATION; HEMISPHERE; ISCHEMIA;

D O I：

10.1073/pnas.1404109111

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：12913 / 12918

页数：6

共 51 条

[1]

Ministrokes in Channelrhodopsin-2 Transgenic Mice Reveal Widespread Deficits in Motor Output Despite Maintenance of Cortical Neuronal Excitability [J].