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.
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.
|Skiba, Rafal M; Snow, Jacqueline C (2016) Attentional capture for tool images is driven by the head end of the tool, not the handle. Atten Percept Psychophys 78:2500-2514|
|Erlikhman, Gennady; Caplovitz, Gideon P (2016) Decoding information about dynamically occluded objects in visual cortex. Neuroimage :|
|Moreno-Bravo, Juan A; Martinez-Lopez, Jesus E; Madrigal, M Pilar et al. (2016) Developmental guidance of the retroflex tract at its bending point involves Robo1-Slit2-mediated floor plate repulsion. Brain Struct Funct 221:665-78|
|Gruner, Hannah; CortÃ©s-LÃ³pez, Mariela; Cooper, Daphne A et al. (2016) CircRNA accumulation in the aging mouse brain. Sci Rep 6:38907|
|Stephens, Jaclyn A; Berryhill, Marian E (2016) Older Adults Improve on Everyday Tasks after Working Memory Training and Neurostimulation. Brain Stimul 9:553-9|
|Zhang, Yong; Lamba, Pallavi; Guo, Peiyi et al. (2016) miR-124 Regulates the Phase of Drosophila Circadian Locomotor Behavior. J Neurosci 36:2007-13|
|Erlikhman, Gennady; Gurariy, Gennadiy; Mruczek, Ryan E B et al. (2016) The neural representation of objects formed through the spatiotemporal integration of visual transients. Neuroimage 142:67-78|
|Downing, Laura E; Ferguson, Bradley S; Rodriguez, Kelvin et al. (2016) A grape seed procyanidin extract inhibits HDAC activity leading to increased PparÎ± phosphorylation and target-gene expression. Mol Nutr Food Res :|
|Kim, Kyung-Tai; Kim, Namhee; Kim, Hwan-Ki et al. (2016) ISL1-based LIM complexes control Slit2 transcription in developing cranial motor neurons. Sci Rep 6:36491|
|Bjorke, Brielle; Shoja-Taheri, Farnaz; Kim, Minkyung et al. (2016) Contralateral migration of oculomotor neurons is regulated by Slit/Robo signaling. Neural Dev 11:18|
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