Single-nucleus RNA-seq of mouse cortex following CCI-induced traumatic brain injury across multiple time points
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE277487 | GEO | 2026/04/24
REPOSITORIES: GEO
Similar Datasets
Project description:This study investigates the effects of controlled cortical impact (CCI), a form of traumatic brain injury (TBI), using a 3D silk scaffold cell culture model. Human induced neural stem cells (iNSCs), human induced astrocytes, and HMC3 microglial cells were seeded onto the silk scaffolds and allowed to grow under controlled conditions. A subset of these cell cultures was then subjected to CCI to simulate injury. The primary aim of the study was to assess the cellular and molecular response to CCI, particularly focusing on miRNA expression profiles. miRNA Nanostring technology was employed to quantify differential expression patterns associated with CCI exposure, providing insights into neuroinflammatory, regenerative, and apoptotic pathways impacted by the injury. These data contribute to a better understanding of miRNA's role as a biomarker for TBI and its potential involvement in cellular recovery and neuroprotection processes following traumatic injury.
2024-12-11 | GSE280043 | GEO
Project description:This study analyzed the effect of RBM5 gene deletion in cortical brain tissue on differential gene expression/splicing changes 48h after a traumatic brain injury (TBI). TBI was induced in WT vs. KO mice by controlled cortical impact (CCI) injury. The four grouops included: (1) Sham-WT, (2) CCI-WT, (3) Sham-KO, and (4) CCI-KO. The objective of this study was to test if RBM5 KO decreased the expression of cell death mediators in the contused brain 48h post-injury.
2021-05-12 | GSE128543 | GEO
Project description:In contrast to the considerable in vitro and in vivo data demonstrating a decrease in cytochrome P450 (CYP) activity in inflammation and infection, clinically, traumatic brain injury (TBI) results in an increase in CYP and UDP glucuronosyltransferases (UGT) activity. The objective of this study was to determine the effects of TBI alone and along with treatment with either erythropoietin (EPO) or anakinra on gene expression of hepatic inflammatory proteins and drug metabolizing enzymes and transporters in a cortical contusion impact (CCI) injury animal model. Microarray-based transcriptional profiling was used to determine the effect on gene expression at 24 h, 72 h and 7 days post-CCI.
2015-06-01 | GSE64886 | GEO
Project description:Traumatic brain injury (TBI) is a major cause of long-term neurological impairment, with aging amplifying vulnerability and worsening recovery. Older individuals face greater cognitive and motor deficits post-TBI and respond less effectively to treatments, as both aging and TBI independently elevate neuroinflammation and cognitive decline. This study evaluated the therapeutic effects of human adipose-derived stem cell small extra-cellular vesicles (hASC-sEVs) on neurological recovery and neuroinflammation in a mouse model of TBI. Male C57BL/6 mice (3, 15, and 20 months old) underwent controlled cortical impact (CCI) and received intranasal hASC-sEVs 48 h post-injury; control groups received PBS. A dose–response study at 7 days post injury (dpi) identified 20 µg as the optimal therapeutic dose, improving motor function, reducing neuroinflammation, and enhancing neurogenesis. This was followed by a 30-dpi study assessing cognitive function, neuroinflammation, neurogenesis, and proteomic changes in microglia and astrocytes via mass spectrometry. hASC-sEV treatment significantly improved behavioral out-comes and reduced neuroinflammatory markers (GFAP, IBA-1, and MHC-II), with re-duced efficacy observed in older mice. Proteomics revealed that hASC-sEVs reduce in-flammatory proteins (TNF-α, IL-1β, IFNG, CCL2) and modulated mitochondrial dysfunction and reactive oxygen species. These results highlight hASC-sEVs as a promising cell-free therapy for improving TBI outcomes, especially in aging populations.
2025-09-11 | PXD067584 | Pride
Project description:Traumatic brain injury (TBI) initiates not only complex neurovascular and glial changes within the brain but also pathophysiological responses that extend beyond the central nervous system. The peripheral response to TBI has become an intensive area of research, as these systemic perturbations can induce dysfunction in multiple organ systems. As there are no approved therapeutics for TBI, it is imperative that we investigate the peripheral response to TBI to identify targets for future intervention. Of particular interest is the gastrointestinal (GI) system. Even in the absence of polytrauma, brain-injured individuals are at increased risk of suffering from GI-related morbidity and mortality. Symptoms such as intestinal dysmotility, inflammation, ulceration, and fecal incontinence can drastically diminish quality of life. The GI tract is inhabited by trillions of microbes that have been implicated as modulators of many neurological disorders. Clinical and preclinical studies implicate gut dysbiosis, a pathological imbalance in the normally symbiotic microbiota, as both a consequence of TBI as well as a contributing factor to brain damage. However, our understanding of this interplay is still limited. While relatively little is known about the effects of TBI on the structure and function of the GI tract, prior studies report that experimental TBI induces intestinal barrier dysfunction and morphological changes. To confirm these findings in the current model of TBI, male C57BL/6J mice underwent a sham control or a controlled cortical impact (CCI) procedure to induce a contusive brain injury, and intestinal permeability was assessed at 4 h, 8 h, 1 d, and 3 d post-injury. An acute, transient increase in permeability was observed at 4 h after CCI. Histological analyses of the ileum and colon at multiple time points from 4 h to 4 wks revealed no overt morphological changes, suggesting that CCI induced a short-lived physiologic dysfunction without major structural alterations to the GI tract. As the microbiome is a modulator of GI physiology, we performed 16s gene sequencing on fecal samples collected prior to and over the first month after CCI or sham injury. Microbial community diversity was assessed using common metrics of alpha and beta diversity. Alpha diversity was lower in the CCI injury group and beta diversity differed among groups, although these effects were not observed in all metrics. Subsequent differential abundance analysis revealed that the phylum Verrucamicrobiota was increased in CCI mice at 1, 2, and 3 d post-injury when compared to sham mice. Subsequent qPCR identified the Verrucamicrobiota species as Akkermansia Muciniphila, an obligate anaerobe that resides in and helps regulate the intestinal mucus layer and barrier. To determine whether TBI promotes changes to the GI tract favorable for the proliferation of A. muciniphila, mucus-producing goblet cells and the level of GI hypoxia were evaluated. Goblet cell density in the medial colon was significantly increased at 1 d, while colon hypoxia was significantly increased at 3 d. Taken together, these studies show that CCI induces transient intestinal barrier dysfunction followed by increased goblet cell density and hypoxia in the colon with a concomitant increase in A. muciniphila that may suggest a compensatory response to systemic stress after TBI.
2024-01-31 | GSE239472 | GEO
Project description:Astrocytes, the most abundant glial cells in the central nervous system (CNS), play a critical role in brain injury responses. While NeuroD1 overexpression in astrocytes has been shown to reverse glial scar formation and promote tissue repair in mouse models of traumatic brain injury (TBI), the underlying molecular mechanisms remain incompletely understood. To address this, we performed single-cell transcriptomic analysis on a controlled cortical impact (CCI) mouse model using recombinant adeno-associated virus (rAAV)-mediated astrocyte-specific NeuroD1 overexpression.Our findings demonstrate that NeuroD1 overexpression suppresses microglial activation and mitigates brain damage post-TBI. Single-cell RNA sequencing revealed significant shifts in astrocyte subtypes, with upregulated neuroinflammatory pathways and downregulated oxygen metabolism in TBI mice. Conversely, NeuroD1 overexpression reshaped astrocyte subpopulation dynamics, enhanced oxygen metabolism-related gene expression, and attenuated neuroinflammatory signaling. This study provides a comprehensive transcriptomic dataset detailing cellular and astrocyte subtype-specific changes following NeuroD1-mediated brain repair. These insights advance our understanding of cell fate modulation in TBI and support the development of NeuroD1-based gene therapies, offering a valuable resource for future TBI research and therapeutic strategies.
2025-11-01 | GSE305371 | GEO
Project description:Using an experimental TBI rat model of mild/moderate Controlled Cortical Impact (CCI) injury, we combined large-scale proteomics identification and relative quantification using Spatially-Resolved Microproteomics with MALDI MS Imaging of Lipids. Spatially by studying different regions in the brain post injury in a coronal view, with main focus on the injury site itself. Temporally by studying the acute and subacute phase post injury, including injured rat brains at 1 day, 3 days, 7 days, and 10 days post injury. Direct on-tissue micro-digestion followed by micoextraction from 1 mm2 surface area within the injured cortical tissue were subjected to LC-MS & MS/MS analysis using HR MS. In addition, several identified potential biomarkers within our study were used to stimulate dorsal root ganglion (DRG), astrocyte, and macrophage cell lines to obtain a better understanding of their role and contribution in the injury.
2019-06-19 | PXD011262 | Pride
Project description:We examined the impact of Abca1 deficiency and APOE isoform expression on the response to TBI using 3-months-old, human APOE3+/+ (E3/Abca1+/+) and APOE4+/+ (E4/Abca1+/+) targeted replacement mice, and APOE3+/+ and APOE4+/+ mice with only one functional copy of the Abca1 gene (E3/Abca1+/-; E4/Abca1+/-). TBI-treated mice received a craniotomy followed by a controlled cortical impact (CCI) brain injury in the left hemisphere; sham-treated mice received the same surgical procedure without the impact. We performed RNA-seq using samples from cortices and hippocampi collected at 14 days post-injury, followed by genome-wide differential gene expression analysis.
2018-07-31 | GSE117223 | GEO
Project description:Objectives: The aim of this study was to reveal the transcriptomic profile of the cerebral cortex in traumatic brain injury (TBI) mice. Methods: A controlled cortical impact (CCI) device was used to establish a TBI model. The gene expression in the cerebral cortex was detected by whole-transcriptome sequencing (RNA-Seq).
2023-06-01 | GSE205958 | GEO
Project description:Abstract Background Traumatic brain injury (TBI) results in irreversible damage at the site of impact and initiates cellular and molecular processes that lead to secondary neural injury in the surrounding tissue. We used microarray analysis to determine which genes, pathways and networks were significantly altered using a rat model of TBI. Adult rats received a unilateral controlled cortical impact (CCI) and were sacrificed 24h post-injury. The ipsilateral hemi-brain tissue at the site of the injury, the corresponding contralateral hemi-brain tissue, and naM-CM-/ve (control) brain tissue were used for microarray analysis. Ingenuity Pathway Analysis (IPA) software was used to identify molecular pathways and networks that were associated with the altered gene expression in brain tissues following TBI. Results Inspection of the top fifteen biological functions in IPA associated with TBI in the ipsilateral tissues revealed that all had an inflammatory component. IPA analysis also indicated that inflammatory genes were altered on the contralateral side, but many of the genes were inversely expressed compared to the ipsilateral side. The contralateral gene expression pattern suggests a remote anti-inflammatory molecular response. We created a network of the inversely expressed common (i.e., same gene changed on both sides of the brain) inflammatory response (IR) genes and those IR genes included in pathways and networks identified by IPA that changed on only one side. We ranked the genes by the number of direct connections each had in the network, creating a gene interaction hierarchy (GIH). Two well characterized signaling pathways, toll-like receptor/NF-kappaB signaling and JAK/STAT signaling, were prominent in our GIH. Conclusions Bioinformatic analysis of microarray data following TBI identified key molecular pathways and networks associated with neural injury following TBI. The GIH created here provides a starting point for investigating therapeutic targets in a ranked order that is somewhat different than what has been presented previously. In addition to being a vehicle for identifying potential targets for post-TBI therapeutic strategies, our findings can also provide a context for evaluating the potential of therapeutic agents currently in development. The ipsilateral hemi-brain tissue at the site of the injury, the corresponding contralateral hemi-brain tissue, and naM-CM-/ve (control) brain tissue (n=3 for each) were used for RNA isolation. The TBI injured animals were Todd 1, 2 Todd, and Todd 3, each yielding an ispilateral and contralateral sample. The naM-CM-/ve animals were Xu 13 control, Xu 2 control, and Xu 6 control.
2013-04-12 | E-GEOD-45997 | biostudies-arrayexpress