Transplantation of primed human fetal neural stem cells improves cognitive function in rats after traumatic brain injury

Gao, Junling; Prough, Donald S.; McAdoo, David J.; Grady, James J.; Parsley, Margaret A.; Ma, Lina; Tarensenko, Yevgeniya I.; Wu, Ping

doi:10.1016/j.expneurol.2006.04.039

Cited by 146 publications

(117 citation statements)

References 68 publications

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“…4,16,18 Rectal and temporalis muscle temperatures were monitored throughout the surgery. Sham-injured rats were connected to the fluid percussion trauma device without injury.…”

Section: Animals and Fluid Percussion Traumatic Brain Injurymentioning

confidence: 99%

“…18 All procedures were approved by the Institutional Animal Care and Use Committee of the University of Texas Medical Branch, and were performed under aseptic conditions in compliance with the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals. Ten male Sprague-Dawley (SD) rats (300 g; Charles River Laboratories International, Inc., Wilmington, MA) were randomly divided into two groups: sham and TBI, five rats per group.…”

Section: Animals and Fluid Percussion Traumatic Brain Injurymentioning

confidence: 99%

“…To make a comparison of the current proteomics analysis with our previous transplantation studies, all animals received 1 lL vehicle injection into the hippocampal region on the injury side 1 day after TBI, and received cyclosporine in the drinking water as previously described. 18 Tissue processing, protein extraction, tryptic digestion and 18 O-labeling Four days after TBI the hippocampus ipsilateral to the injury was removed and the CA3 dissected from the remainder of the hippocampus under magnification with a dissecting microscope and processed as previously described. 57,62,67,70,81 The 4-day time point was chosen because: (1) it is between the peaks of injuryinduced inflammation 60 and of reactive astrogliosis, 55 (2) there are metabolic changes during this time, 31,34 and (3) it allows settlement of grafted and host cells after surgery for future studies aimed to compare TBI-injured animals with and without cell transplantation.…”

Section: Animals and Fluid Percussion Traumatic Brain Injurymentioning

confidence: 99%

“…33,38 Previously, we reported that grafting human neural stem cells (hNSCs) into the injured hippocampus acutely improved cognitive function of TBI rats. 18 However, the underling mechanisms remain elusive, and require a basic knowledge of how TBI changes the overall systems biology of protein expression in the host hippocampus. Because of the varied signaling pathways, unique cellular architecture, and electrophysiological properties within each of the subregions of the hippocampus, in this study we focused particularly on the CA3 region, which is the gateway for information flow into and processing within the hippocampus.…”

Section: Introductionmentioning

confidence: 99%

“…20,51,65 A variety of metabolic, chemical, and enzymatic methods have been developed for stable isotope labeling. 21,50 Here, we used stable isotope 18 O-water differential labeling, 27,78 2D liquid chromatographymass spectrometry/mass spectrometry (2D-LC-MS/MS), and bioinformatics tools to identify proteins that are unaffected, upregulated, and downregulated in the CA3 region of the hippocampus by TBI in a rat fluid percussion model. This systems biology approach provides a higher-level knowledge base of the integrative molecular mechanisms of TBI, insights into key regulatory networks and their regulatory nodes, and lays the groundwork for the discovery of novel therapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

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Detection of Structural and Metabolic Changes in Traumatically Injured Hippocampus by Quantitative Differential Proteomics

Zhao

Haidacher

et al. 2013

Journal of Neurotrauma

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Traumatic brain injury (TBI) is a complex and common problem resulting in the loss of cognitive function. In order to build a comprehensive knowledge base of the proteins that underlie these cognitive deficits, we employed unbiased quantitative mass spectrometry, proteomics, and bioinformatics to identify and quantify dysregulated proteins in the CA3 subregion of the hippocampus in the fluid percussion model of TBI in rats. Using stable isotope 18 O-water differential labeling and multidimensional tandem liquid chromatography (LC)-MS/MS with high stringency statistical analyses and filtering, we identified and quantified 1002 common proteins, with 124 increased and 76 decreased. The Ingenuity Pathway Analysis (IPA) bioinformatics tool identified that TBI had profound effects on downregulating global energy metabolism, including glycolysis, the Krebs cycle, and oxidative phosphorylation, as well as cellular structure and function. Widespread upregulation of actin-related cytoskeletal dynamics was also found. IPA indicated a common integrative signaling node, calcineurin B1 (CANB1, CaNBa, or PPP3R1), which was downregulated by TBI. Western blotting confirmed that the calcineurin regulatory subunit, CANB1, and its catalytic binding partner PP2BA, were decreased without changes in other calcineurin subunits. CANB1 plays a critical role in downregulated networks of calcium signaling and homeostasis through calmodulin and calmodulin-dependent kinase II to highly interconnected structural networks dominated by tubulins. This large-scale knowledge base lays the foundation for the identification of novel therapeutic targets for cognitive rescue in TBI.

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“…4,16,18 Rectal and temporalis muscle temperatures were monitored throughout the surgery. Sham-injured rats were connected to the fluid percussion trauma device without injury.…”

Section: Animals and Fluid Percussion Traumatic Brain Injurymentioning

confidence: 99%

Section: Animals and Fluid Percussion Traumatic Brain Injurymentioning

confidence: 99%