Role of neuronal stem cell migration in brain repair following ischemic stroke Our long-term goal is to provide evidence for the ultimate development of direct-current electrical field (EF) as a novel brain repair and neuroprotection therapy for stroke patients. Brain ischemia induces proliferation of neural stem/progenitor cells (NSPCs) in the subventricular zone (SVZ). Although the newly generated NSPCs can differenfiate into new neurons that migrate to the damaged regions, only a fraction of the new neurons is found to migrate to the damaged area, which is a critical barrier to prevent endogenous neuroregenerafion. Yet, little effort has been made towards identifying guidance cues that promote NSPC migration to overcome the barrier. Our study suggests that the EF may be one such guidance cue. As EF is potenfially safe in human CNS, EF sfimulafion may be developed as brain repair and neuroprotecfion therapy. We have shown that EF stimulation guides and accelerates NSPC migrafion towards the cathode in vitro, and this migrafion requires interaction of N-methyl-D-aspartate receptors (NMDARs) with Rho GTPase Racl/acfin signaling. Funcfional NMDARs are redistributed to the cathode side of EF-exposed NSPCs, suggesfing a role of polarized NMDARs in mediafing EF-directed NSPC migrafion. Importantly, our preliminary study has shown that a non-invasive EF sfimulafion promotes migration of SVZ NSPC-derived new neurons, towards the cathode direction, to the ischemic boundary zone in an in vivo rat stroke model. In this project, we will continue to use the rat stroke model to test the hypothesis that EF stimulation guides and accelerates the migration of funcfional, SVZ NPSC-derived new neurons to the damaged brain region and promotes functional recovery through NMDAR-dependent Racl/actin signal pathway. We will first determine whether EF sfimulafion directs migrafion of funcfional new neurons to the damaged brain region and improves neurobehavioral outcome of stroke animals. We will then determine the role of NMDAR/Racl/acfin signaling in mediafing EF-induced NSPC migrafion in the ischemic brain. The outcome of this study will lead us to understand how EF directs NSPC migrafion in stroke model in vivo, which is essential for the ultimate development of EF sfimulation as a novel brain repair and/or neuroprotection strategy.

Public Health Relevance

Stroke is a disease that affects the arteries leading to and within the brain. It is the No. 3 cause of death in the United States. The aim of our study is to provide scientific evidence to support the development of novel brain repair therapy for stroke pafients.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
1P20GM103650-01
Application #
8479256
Study Section
Special Emphasis Panel (ZRR1-RI-4 (01))
Project Start
Project End
Budget Start
2012-09-05
Budget End
2013-05-31
Support Year
1
Fiscal Year
2012
Total Cost
$268,279
Indirect Cost
$68,945
Name
University of Nevada Reno
Department
Type
DUNS #
146515460
City
Reno
State
NV
Country
United States
Zip Code
89557
Vercillo, Tiziana; Jiang, Fang (2017) Spatial modulation of motor-sensory recalibration in early deaf individuals. Neuropsychologia 102:39-44
Yang, Wen-Yan; Tang, Xiao-Tian; Ju, Rui-Ting et al. (2017) The population genetic structure of Corythucha ciliata (Say) (Hemiptera: Tingidae) provides insights into its distribution and invasiveness. Sci Rep 7:635
Downing, Laura E; Ferguson, Bradley S; Rodriguez, Kelvin et al. (2017) A grape seed procyanidin extract inhibits HDAC activity leading to increased Ppar? phosphorylation and target-gene expression. Mol Nutr Food Res 61:
Vercillo, Tiziana; Carrasco, Carlos; Jiang, Fang (2017) Age-Related Changes in Sensorimotor Temporal Binding. Front Hum Neurosci 11:500
Stephens, Jaclyn A; Jones, Kevin T; Berryhill, Marian E (2017) Task demands, tDCS intensity, and the COMT val158met polymorphism impact tDCS-linked working memory training gains. Sci Rep 7:13463
Chen, Siqi; Zaeimian, Masoumeh Saber; Monteiro, Jorge H S K et al. (2017) Mn Doped AIZS/ZnS Nanocrystals: Synthesis and Optical Properties. J Alloys Compd 725:1077-1083
Strother, Lars; Zhou, Zhiheng; Coros, Alexandra K et al. (2017) An fMRI study of visual hemifield integration and cerebral lateralization. Neuropsychologia 100:35-43
Zhou, Zhiheng; Strother, Lars (2017) Distinct effects of contour smoothness and observer bias on visual persistence. J Vis 17:8
Kim, Minkyung; Fontelonga, Tatiana M; Lee, Clare H et al. (2017) Motor axons are guided to exit points in the spinal cord by Slit and Netrin signals. Dev Biol 432:178-191
Gomez, Michael A; Snow, Jacqueline C (2017) Action properties of object images facilitate visual search. J Exp Psychol Hum Percept Perform 43:1115-1124

Showing the most recent 10 out of 78 publications