Browsing by Author "Seekaew, Pich"

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    mTOR SIGNALING MEDIATES TBI-ENHANCED NEURAL STEM CELL PROLIFERAION
    (Office of the Vice Chancellor for Research, 2012-04-13) Seekaew, Pich; Chen, Liang; Gao, Xiang; Chen, Jinhui
    Traumatic Brain Injury (TBI) induced neuron death was once thought to be irreversible. However, the identification of neural stem cells (NSCs) in the adult brain holds the hope of repairing injured brain following TBI. Our pre-vious study showed that TBI promotes NSC proliferation in an attempt to ini-tial an innate repair and/or plasticity mechanisms. However, this induced proliferation is transient without significantly increasing neurogenesis. It suggests that additional intervention is required to further increase NSC pro-liferation to enhance neurogenesis for successfully repairing the damaged brain following TBI. In order to determine the molecular mechanism that mediates TBI-enhanced NSC proliferation, we assessed the activity of mam-malian target of rapamycin (mTOR) signaling by detecting the level of Phospho-S6 Ribosomal protein (pS6), an indicator of the activity of mTOR signaling. We found that the level of pS6 was transient but dramatically in-creased prior to TBI-enhanced NSC proliferation. In contrast inhibiting the activity of mTOR signaling with rapamycin attenuated this effect, indicating that mTOR signaling mediates TBI-enhanced NSC proliferation. Further stimulating mTOR signaling strengthened the effect of TBI-enhanced NSC proliferation. These results suggest that mTOR signaling mediates TBI-enhanced neural stem cell proliferation and stimulating mTOR signaling may be a potential therapeutic approach to enhance neurogenesis for post-traumatic functional recovery.
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    Traumatic Brain Injury Stimulates Neural Stem Cell Proliferation via Mammalian Target of Rapamycin Signaling Pathway Activation
    (Society for Neuroscience, 2016-09) Wang, Xiaoting; Seekaew, Pich; Gao, Xiang; Chen, Jinhui; Department of Neurological Surgery, School of Medicine
    Neural stem cells in the adult brain possess the ability to remain quiescent until needed in tissue homeostasis or repair. It was previously shown that traumatic brain injury (TBI) stimulated neural stem cell (NSC) proliferation in the adult hippocampus, indicating an innate repair mechanism, but it is unknown how TBI promotes NSC proliferation. In the present study, we observed dramatic activation of mammalian target of rapamycin complex 1 (mTORC1) in the hippocampus of mice with TBI from controlled cortical impact (CCI). The peak of mTORC1 activation in the hippocampal subgranular zone, where NSCs reside, is 24-48 h after trauma, correlating with the peak of TBI-enhanced NSC proliferation. By use of a Nestin-GFP transgenic mouse, in which GFP is ectopically expressed in the NSCs, we found that TBI activated mTORC1 in NSCs. With 5-bromo-2'-deoxyuridine labeling, we observed that TBI increased mTORC1 activation in proliferating NSCs. Furthermore, administration of rapamycin abolished TBI-promoted NSC proliferation. Taken together, these data indicate that mTORC1 activation is required for NSC proliferation postinjury, and thus might serve as a therapeutic target for interventions to augment neurogenesis for brain repair after TBI.