The hippocampus on Blast-related Traumatic Brain Injury at Single-cell Resolution
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE230253 | GEO | 2023/09/04
REPOSITORIES: GEO
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Project description:To elucidate molecular features of the cells of Sub-ventricular Zone (SVZ), their progeny at each differentiation stage, and surrounding cells in SVZ under blast wave-induced changes, cells were profiled from matched SVZ of 3 mice that had received blast injury and 3 controls（The controls sequencing profile can be assessed in GEO at GSM5938054）.Cell type specific gene expression responding to (blast-related traumatic brain injury, bTBI) were revealed, some of which were closely associated with pathogenesis post-injury. Furthermore, the diverse cell to cell interaction networks uncovered an array of cellular processes under bTBI. Our gene expression atlas provides extensive resources for future researches regarding bTBI induced pathogenesis, its therapeutic interventions or diagnostic tests.
2022-06-28 | GSE207078 | GEO
Project description:Warfare has long been associated with traumatic brain injury (TBI) in militarized zones. Common forms of TBI can be caused by a physical insult to the head-brain or by the effects of a high velocity blast shock wave generated by the detonation of an explosive device. While both forms of trauma are distinctly different regarding the mechanism of trauma induction, there are striking similarities in the cognitive and emotional status of survivors. Presently, proven effective therapeutics for the treatment of either form of TBI are unavailable. To be able to develop efficacious therapies, studies involving animal models of physical- and blast-TBI are required to identify possible novel or existing medicines that may be of value in the management of clinical events. We examined indices of cognition and anxiety-like behavior and the hippocampal gene transcriptome of mice subjected to both forms of TBI. We identified common behavioral deficits and gene expression regulations, in addition to unique injury-specific forms of gene regulation. Molecular pathways presented a pattern similar to that seen in gene expression. Interestingly, pathways connected to AlzheimerM-bM-^@M-^Ys disease displayed a markedly different form of regulation depending on the type of TBI. While these data highlight similarities in behavioral outcomes after trauma, the divergence in hippocampal transcriptome observed between models suggests that, at the molecular level, the TBIs are quite different. These models may provide tools to help define therapeutic approaches for the treatment of physical- and blast-TBIs. Based upon observations of increasing numbers of personnel displaying TBI related emotional and behavioral changes in militarized zones, the development of efficacious therapies will become a national if not a global priority. Keywords: Physical-traumatic brain injury; Blast-traumatic brain injury; Cognitive dysfunction; Gene expression; Molecular pathway(s); Neurodegeneration; Stem cells; AlzheimerM-bM-^@M-^Ys disease A mild physical-TBI was induced using a concussive head trauma device described previously (Milman et al., 2005; Zohar et al., 2003). Briefly, mice were lightly anesthetized (Isoflurane) and placed under the weight-drop concussive head trauma instrument. The device consisted of a metal tube (inner diameter 13 mm), placed vertically over the mouse head. A metal weight (30 g) was dropped from the top of the tube (80 cm) and struck the skull at the right side temporal area between the corner of the eye and the ear. A sponge supported the head, allowing some antero-posterior motion without any rotational head movement at the moment of the impact. Experimental conditions used to create a mild low-level blast-TBI and the subsequent model characterization, have been described in detail elsewhere (Rubovitch et al., 2011). In brief, mice were anaesthetized with a combination of ketamine (100 mg/kg) and xylazine (10 mg/kg). Once the animals were fully anaesthetized they were placed at a defined distance from a detonation source, in this case 7 meters. Pressure sensors were used to measure the explosion shock wave pressure (PSI) generated by the detonation (Free-Field ICPM-BM-. Blast Pressure Sensor; PCB Piezoelectronics, Depew, NY, USA, Model 137). At 7 meters from the source of the detonation, the animals were exposed to a maximum of a 2.5 PSI (17.2 kPa) pressure shock wave. Immediately after the induction of the injury, mice were placed back in their cages. Once the animals had recovered from the anesthesia, basic neurological assessments were undertaken to identify any acute neurological dysfunction. Only animals exhibiting no evidence of acute neurological damage post injury were subsequently used in further experiments. Sham treated mouse groups were treated identically; however, they were not exposed to physical- or blast-TBI. Mouse hippocampus tissues were randomly selected from the larger library of samples generated from the behavioral experiments and the numbers utilized in the gene expression study were as follows: sham, n = 5: physical-TBI, n = 4; blast-TBI, n = 7.
2013-03-18 | E-GEOD-44625 | biostudies-arrayexpress
Project description:Warfare has long been associated with traumatic brain injury (TBI) in militarized zones. Common forms of TBI can be caused by a physical insult to the head-brain or by the effects of a high velocity blast shock wave generated by the detonation of an explosive device. While both forms of trauma are distinctly different regarding the mechanism of trauma induction, there are striking similarities in the cognitive and emotional status of survivors. Presently, proven effective therapeutics for the treatment of either form of TBI are unavailable. To be able to develop efficacious therapies, studies involving animal models of physical- and blast-TBI are required to identify possible novel or existing medicines that may be of value in the management of clinical events. We examined indices of cognition and anxiety-like behavior and the hippocampal gene transcriptome of mice subjected to both forms of TBI. We identified common behavioral deficits and gene expression regulations, in addition to unique injury-specific forms of gene regulation. Molecular pathways presented a pattern similar to that seen in gene expression. Interestingly, pathways connected to Alzheimer’s disease displayed a markedly different form of regulation depending on the type of TBI. While these data highlight similarities in behavioral outcomes after trauma, the divergence in hippocampal transcriptome observed between models suggests that, at the molecular level, the TBIs are quite different. These models may provide tools to help define therapeutic approaches for the treatment of physical- and blast-TBIs. Based upon observations of increasing numbers of personnel displaying TBI related emotional and behavioral changes in militarized zones, the development of efficacious therapies will become a national if not a global priority. Keywords: Physical-traumatic brain injury; Blast-traumatic brain injury; Cognitive dysfunction; Gene expression; Molecular pathway(s); Neurodegeneration; Stem cells; Alzheimer’s disease
2013-03-18 | GSE44625 | GEO
Project description:Traumatic brain injury (TBI) remains a leading cause of post traumatic epilepsy (PTE). Blast TBI (bTBI) found in Veterans presents cognitive and behavioral disturbance such as PTE, however, the underlying mechanisms that drive the long-term sequelae are not well understood. Using an unbiased proteomics approach in a murine model of repeated bTBI (rbTBI), this study addresses this gap in knowledge. Following rbTBI, mice underwent 24/7 EEG recording for four months before collecting the cortex and hippocampus of PTE+, PTE- and sham mice. Hundreds of differentially expressed proteins were identified in the cortex and hippocampus of PTE+ and PTE- relative to sham. Focusing on protein pathways unique to PTE+ animals revealed mitochondrial function, post translational modifications, and protein transport proteins were disrupted. Computational metabolic modeling using dysregulated protein expression predicted mitochondrial proton pump dysregulation, suggesting electron transport chain dysregulation in epileptic tissue relative to PTE- and sham. Finally, data mining enabled the identification of several novel and previously validated TBI and epilepsy biomarkers in our data set, many of which were found to already be targeted by drugs in various phases of clinical testing. These findings highlight novel proteins and protein pathways that may drive the chronic PTE sequala following rbTBI.
2024-06-22 | PXD048228 | Pride
Project description:Primary blast-induced mild traumatic brain injury (mTBI) represents a common injury experienced during modern warfare. With virtually no apparent physical damage or symptoms presented, an effective source with minimum-invasion for mTBI biomarker discovery is required. In this study, we measure the transcriptomic sensitivity of the hair follicles in relation to the severity of primary blast-derived TBI.
2016-05-07 | GSE80371 | GEO
Project description:The subventricular zone (SVZ) is a neurogenetic niche that contributes to homeostasis and repair after brain injury. However, effects of mild traumatic brain injury (mTBI) on genomewide gene expression in the SVZ remain largely unexplored. To address this issue, we investigated the single-nucleus transcriptomic profiles of the SVZ after mTBI. 18 distinct clusters were yielded via unsupervised clustering of the transcriptomic profiles. Cell type specific gene expression responding to mTBI were revealed, some of which were closely associated with pathogenesis post-injury. Furthermore, the diverse cell to cell interaction networks uncovered an array of cellular processes under mTBI. Also, we reported novel lineage trajectories and molecular hallmarks that govern the neurogenesis. Our gene expression atlas provides extensive resources for future researches regarding mTBI induced pathogenesis, its therapeutic interventions or diagnostic tests.
2022-06-28 | GSE198074 | GEO
Project description:Blast traumatic brain injury (B-TBI) affects military and civilian personnel. Presently there are no approved drugs for blast brain injury. Exendin-4, administered subcutaneously, was evaluated as a pre-treatment (48 hours) and post-injury treatment (2 hours) on neurodegeneration, behaviors and gene expressions in a murine open field model of blast injury. B-TBI induced neurodegeneration, changes in cognition and genes expressions linked to dementia disorders. Exendin-4, administered pre- or post-injury ameliorated B-TBI-induced neurodegeneration at 72 hours, memory deficits from days 7-14 and attenuated genes regulated by blast at day 14 post-injury. The present data suggest shared pathological processes between concussive and B-TBI, with endpoints amenable to beneficial therapeutic manipulation by exendin-4. B-TBI-induced dementia-related gene pathways and cognitive deficits in mice somewhat parallel epidemiological studies of Barnes and co-workers who identified a greater risk in US military veterans who experienced diverse TBIs, for dementia in later life.
2016-08-05 | GSE71846 | GEO
Project description:Traumatic brain injuries (TBI) of varied types are common across all populations and can cause visual problems. For military personnel in combat settings, injuries from blast exposures (bTBI) are prevalent and arise from a myriad of different situations. To model these diverse conditions, we are one of several groups modeling bTBI using mice in varying ways. Here, we report a refined analysis of retinal ganglion cell (RGC) damage in male C57BL/6J mice exposed to a blast-wave in an enclosed chamber. Ganglion cell layer thickness, RGC density (BRN3A and RBPMS immunoreactivity), cellular density of ganglion cell layer (hematoxylin and eosin staining), and axon numbers (paraphenylenediamine staining) were quantified at timepoints ranging from 1 to 17-weeks. RNA sequencing was performed at 1-week and 5-weeks post-injury. Earliest indices of damage, evident by 1-week post-injury, are a loss of RGC marker expression, damage to RGC axons, and increase in glial markers expression. Blast exposure caused a loss of RGC somas and axons-with greatest loss occurring by 5-weeks post-injury. While indices of glial involvement are prominent early, they quickly subside as RGCs are lost. The finding that axonopathy precedes soma loss resembles pathology observed in mouse models of glaucoma, suggesting similar mechanisms.
2024-08-14 | GSE274793 | GEO
Project description:These data show differences in up- and down-regulation for protein abundances in the hippocampus of double blast vs. sham rats. Tandem mass tags (TMT)-MS results showed 136 up-regulated and 94 down-regulated proteins between the two groups. These TMT-MS findings revealed changes never described before in blast studies. In the absence of behavioral changes, these proteomic data further support the existence of an asymptomatic blast-induced molecular altered status (ABIMAS) associated with specific protein changes in the rat hippocampus.
| MSV000092956 | MassIVE
Project description:Meningeal lymphatic dysfunction exacerbates traumatic brain injury pathogenesis
| PRJNA648368 | ENA