Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neuroprotective potential of intranasally delivered L-myc immortalized human neural stem cells in female rats after a controlled cortical impact injury

ABSTRACT: Efficacious stem cell-based therapies for traumatic brain injury (TBI) depend on successful delivery, migration, and engraftment of stem cells to induce neuroprotection. L-myc expressing human neural stem cells (LMNSC008) demonstrate an inherent tropism to injury sites after intranasal (IN) administration. We hypothesize that IN delivered LMNSC008 cells migrate to primary and secondary injury sites and modulate biomarkers associated with neuroprotection and tissue regeneration. To test this, immunocompetent adult female rats received a controlled cortical impact injury (CCI) or sham surgery. LMNSC008 cells or a vehicle (VEH) were administered IN on postoperative days 7, 9, 11, 13, 15, and 17. The distribution and migration of eGFP-expressing LMNSC008 cells were quantified over 1 mm-thick optically cleared (CLARITY) coronal brain sections from TBI and SHAM controls. NSC migration was observed along white matter tracts projecting toward the hippocampus and regions of TBI. ELISA and Nanostring assays revealed a shift in tissue gene expression in LMNSC008 treated rats relative to controls. LMNSC008 treatment reduced expression of genes and pathways involved in inflammatory response, microglial function, and various cytokines and receptors. The data demonstrate a robust proof-of-concept for LMNSC008 therapy for TBI and provides a strong rationale for IN delivery for translation in TBI patients. NanoString RNAseq sample preparation and data acquisition

ORGANISM(S): Mus musculus Rattus norvegicus

PROVIDER: GSE242031 | GEO | 2024/02/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Proteomics characterization of the neuroprotective effects of low-dose methamphetamine on rats with traumatic brain injury (TBI)

Project description:Traumatic brain injury (TBI) causes hospitalizations and mortality worldwide with no approved neuroprotective treatments available, partly due to a poor understanding of the molecular mechanisms underlying TBI neuropathology and neuroprotection. We previously reported that the administration of low-dose methamphetamine (MA) induced significant functional/cognitive improvements following severe TBI in rats. We further demonstrated that MA mediates neuroprotection in part, via dopamine-dependent activation of the PI3K-AKT pathway. Here, we further investigated the proteomic changes within the rat cortex and hippocampus following mild TBI (TM), severe TBI (TS), or severe TBI plus MA treatment (TSm) compared to sham operated controls (n=78 in total). We quantified >7,000 unique proteins in total and identified 402 and 801 altered proteins (APs) with high confidence in cortical and hippocampal tissues, respectively. The overall profile of APs observed in TSm rats more closely resembled those seen in TM rather than TS rats. Pathway analysis suggested beneficial roles for acute signaling through IL-6, TGFβ, and IL-1β. Moreover, changes in fibrinogen levels observed in TSm rats suggested a potential role for these proteins in reducing/preventing TBI-induced coagulopathies. These data facilitate further investigations to identify specific pathways and proteins that may serve as key targets for the development of neuroprotective therapies.

2021-03-02 | PXD024317 | Pride

Gene expression of whole hippocampus 24hr post-injury in rat

Project description:Traumatic brain injury (TBI) alters and dysregulates the expression of thousands of genes in the brain. Since some of the most common problems in TBI patients are learning and memory deficits, we are studying the effects of TBI on the hippocampus, a region of the brain which is essential for learning and memory and which is known to be particularly vulnerable to TBI. We are interested in understanding how potential neuroprotective drugs alter the TBI-induced gene expression profile. The objective of this study is to elucidate and compare the differential gene expression profiles in the hippocampus of naive, sham-control, TBI and TBI plus drug treated rats. JM6, PMI-006 and E33 are three compounds with neuroprotective, anti-inflammatory and anti-oxidative effects. Our goal is to determine if different neuroprotective compounds have similar effects on common gene targets. These genes and the cell signaling pathways linked to them would then be the target of new therapeutic strategies for TBI. Rats were prepared for fluid percussion traumatic brain injury or sham injury (naÃ¯ve rats had no anesthesia and were not handled in any way and gene expression in their brains serve as baseline data) and 24 hr post-injury, hippocampi were obtained, and stored in RNA later. Total RNA was isolated, quantitified and used for Agilent microarray analysis at GenUs Biosystems. Each group of naive, sham control, TBI and TBI plus JM6, TBI plus PMI-006 and TBI plus E33 (estrogen) has three biological replicates.

2015-01-08 | E-GEOD-59645 | biostudies-arrayexpress

Transcription profiling of rat brain time series samples treated with lateral fluid percussion injury or sham surgery without injury to investigate the physiological effects of taumatic brain injury

Project description:Traumatic brain injury (TBI) induces a complex cascade of molecular and physiological effects. This study proposes to investigate the gene expression profile in cortex and hippocampus over early time points, following two different injury severities. These results will complement prior knowledge of both metabolic and neuroplastic changes after TBI, as well as serve as a starting point to investigate additional gene families whose expression is altered after TBI.,To characterize the profile of gene expression following a diffuse traumatic brain injury of varying severity in adult rats. ,Distinct patterns of gene expression following traumatic brain injury will occur in a time- and injury-dependent fashion. In particular, changes in expression of enzymes involved in energy metabolism and neuroplasticity will be detected.,Adult rats will be subjected to mild and severe lateral fluid percussion injury OR sham surgery without injury. At various post-injury timepoints (0.5, 4 and 24 hours), animals will be sacrificed, brain regions (parietal cortex and hippocampus, ipsilateral and contralateral to injury) will be dissected and RNA isolated. RNA will be used to synthesize cRNA probes for microarray hybridization. RNA from 2 matched animals will be pooled onto a single chip (U34A rat, Affymetrix). Comparisons will be made between sham and injured animals, with brain region, injury severity, and post-injury time point as the experimental variables.

2007-07-31 | E-GEOD-2871 | biostudies-arrayexpress

miRNA expression of whole hippocampus 24hr post-injury in rat

Project description:Traumatic brain injury dysregulates microRNA expression in the brain. We hypothesized that injury-induced epigenetic changes contribute to neurodegeneration and learning and memory deficits after TBI. These changes may provide a mechanistic explanation for neuropsychiatric comorbidities in TBI patients. Our objective is to compare and contrast the effects of several neuroprotective drugs (JM6, PMI-006 and E33-estrogen) on the TBI-induced changes in microRNA expression in the hippocampus, a region of the brain that is critical for learning and memory. We will also study if different neuroprotective drugs have similar effects on common microRNAs which may cooperatively regulate a common set of gene targets. 3 biological samples each of NaÃ¯ve, Sham control, TBI and TBI plus JM6, TI plus PMI-006, and TBI plus E33 rat hippocampi were obtained 24 hr post-sham injury or TBI, stored in RNA later and sent to GenUs Biosystems for microRNA microarray analysis.

2015-01-08 | E-GEOD-59646 | biostudies-arrayexpress

giza-affy-rat-84719

Project description:Traumatic brain injury (TBI) induces a complex cascade of molecular and physiological effects. This study proposes to investigate the gene expression profile in cortex and hippocampus over early time points, following two different injury severities. These results will complement prior knowledge of both metabolic and neuroplastic changes after TBI, as well as serve as a starting point to investigate additional gene families whose expression is altered after TBI. To characterize the profile of gene expression following a diffuse traumatic brain injury of varying severity in adult rats. Distinct patterns of gene expression following traumatic brain injury will occur in a time- and injury-dependent fashion. In particular, changes in expression of enzymes involved in energy metabolism and neuroplasticity will be detected. Adult rats will be subjected to mild and severe lateral fluid percussion injury OR sham surgery without injury. At various post-injury timepoints (0.5, 4 and 24 hours), animals will be sacrificed, brain regions (parietal cortex and hippocampus, ipsilateral and contralateral to injury) will be dissected and RNA isolated. RNA will be used to synthesize cRNA probes for microarray hybridization. RNA from 2 matched animals will be pooled onto a single chip (U34A rat, Affymetrix). Comparisons will be made between sham and injured animals, with brain region, injury severity, and post-injury time point as the experimental variables. Keywords: time-course

2005-07-06 | GSE2871 | GEO

Timecourse RNAseq for Drosophila TBI

Project description:Comparison of post-injury (sham versus severe TBI) gene expression changes using a Drosophila head-specific TBI model.

2021-07-20 | GSE171185 | GEO

Common molecular signature of two neuroprotective agents

Project description:The current lack of proven pharmacological treatment options for traumatic brain injury (TBI) patients reflects the poor translation of successful preclinical studies in clinical trials. This may be due to poor choice of therapeutic agents based on incomplete knowledge of critical elements of neuroprotection. Our goal is to expedite discovery and translation of therapeutic agents that can improve functional outcome by identifying the common molecular profile of neuroprotective drugs. Since damage to the hippocampus is associated with TBI-induced deficits in learning and memory, we analyzed of the hippocampal transcriptional profiles of TBI rats treated with two clinically used drugs metyrapone and carbenoxolone, which have been shown to improve cognitive deficits in previous studies. Despite their different structures, we found that MT and CB have similar effects on several known biological pathways. The neuroprotective effects of these drugs are associated with a distinctive molecular signature which is characterized not by changes in expression of any individual gene but by a common global effect on multiple cell signaling pathways. These data suggest that drug treatments that induce a coordinated attenuation of multiple injury-induced cell signaling networks, both deleterious and protective, have high translational potential. There were 16 samples for array analysis, two biological replicates each for control (4 and 24 hour), TBI (4 and 24 hour), TBI plus MT (4 and 24 hour) and TBI plus CB (4 and 24 hour). Each biological sample, which is a pooled RNA sample (laser captured CA3 pyramidal neurons) from the hippocampus of 3-6 rats, was hybridized to duplicate arrays so that there were 32 gene arrays in this study.

2012-12-23 | E-GEOD-31357 | biostudies-arrayexpress

Local Delivery of Dual Stem Cell-derived Exosomes using an Electrospun Nanofibrous Platform for the Treatment of Traumatic Brain Injury

Project description:In this study, we developed an electrospun nanofibrous scaffold to provide sustained delivery of dual exosomes derived from mesenchymal stem cells and neural stem cells for TBI treatment.These findings collectively suggest that our novel Duo-Exo@NF system could function as an effective treatment modality for TBI using sustained local delivery of dual exosomes from stem cells.

2023-11-07 | PXD046716 |

Partial Tendon Injury at the Tendon-to-Bone Enthesis Activates Skeletal Stem Cells

Project description:Partial tendon-to-bone interface (TBI) injuries heal in a mechanically inferior manner and redevelop healthy uninjured tissue morphology. The origin of the cells involved in tendon-to-bone healing remains unknown. We employed a rigorous approach to evaluate if mouse skeletal stem cells (mSSC) play a role in tendon-to-bone healing after partial-injury. Using fluorescence-activated cell sorting we identified that found that they are present within the TBI. Using a TBI-injury rainbow lineage tracing mouse model, we demonstrated that injury-responsive cells within the TBI and calcaneus proliferate polyclonally following partial-tendon injury at the TBI. These injury-responsive clonal cells express skeletal marker SP7. We quantified the differences in mSCC frequency after TBI-injury and found that mSSC respond to injury with a higher frequency and have associated changes in gene expression, with the specific down-regulation of the TGFβ signaling pathway. Exogenous delivery of TGFβ after injury was found to reduce the mSSC response after injury. These findings suggest that mSSC may facilitate tendon-to-bone healing by downregulating TGFβ signaling within the mSSC niche.

2022-02-14 | GSE167080 | GEO

microRNA expression in rat hippocampus up to 1 year after fluid percussion brain injury

Project description:Purpose: The goal of this study is to investigate the expression of microRNAs up to 1 year after fluid percussion TBI Methods: miRNA-Seq analysis of microRNA expression in the hippocampus of TBI and sham surgery rats

2020-03-09 | GSE131704 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data