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 patients.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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University of Nevada Reno
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Leonard, Anne S; Masek, Pavel (2014) Multisensory integration of colors and scents: insights from bees and flowers. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 200:463-74
Kim, Minkyung; Farmer, W Todd; Bjorke, Brielle et al. (2014) Pioneer midbrain longitudinal axons navigate using a balance of Netrin attraction and Slit repulsion. Neural Dev 9:17
Gruner, Matthew; Nelson, Dru; Winbush, Ari et al. (2014) Feeding state, insulin and NPR-1 modulate chemoreceptor gene expression via integration of sensory and circuit inputs. PLoS Genet 10:e1004707
McCarthy, J Daniel; Caplovitz, Gideon Paul (2014) Color synesthesia improves color but impairs motion perception. Trends Cogn Sci 18:224-6
Masek, Pavel; Reynolds, Lauren A; Bollinger, Wesley L et al. (2014) Altered regulation of sleep and feeding contributes to starvation resistance in Drosophila melanogaster. J Exp Biol 217:3122-32
Peterson, Dwight J; Gurariy, Gennadiy; Dimotsantos, Gabriella G et al. (2014) The steady-state visual evoked potential reveals neural correlates of the items encoded into visual working memory. Neuropsychologia 63:145-53
Wu, Jingwen; Bao, Jianqiang; Kim, Minkyung et al. (2014) Two miRNA clusters, miR-34b/c and miR-449, are essential for normal brain development, motile ciliogenesis, and spermatogenesis. Proc Natl Acad Sci U S A 111:E2851-7
Gözenman, Filiz; Tanoue, Ryan T; Metoyer, Terina et al. (2014) Invalid retro-cues can eliminate the retro-cue benefit: Evidence for a hybridized account. J Exp Psychol Hum Percept Perform 40:1748-54
Janczyk, Markus; Berryhill, Marian E (2014) Orienting attention in visual working memory requires central capacity: decreased retro-cue effects under dual-task conditions. Atten Percept Psychophys 76:715-24
Jones, Kevin T; Gözenman, Filiz; Berryhill, Marian E (2014) Enhanced long-term memory encoding after parietal neurostimulation. Exp Brain Res 232:4043-54

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