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Transcriptomic Response of Brain Tissue to Focused Ultrasound-Mediated Blood-Brain Barrier Disruption Depends Strongly on Anesthesia - Bulk RNA-seq

ABSTRACT: Transcriptomic Response of Brain Tissue to Focused Ultrasound-Mediated Blood-Brain Barrier Disruption Depends Strongly on Anesthesia - Bulk RNA-seq

PROVIDER: PRJNA638543 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11973428_1.fastq.gz	Fastqsanger.gz
	SRR11973428_2.fastq.gz	Fastqsanger.gz
	SRR11973429_1.fastq.gz	Fastqsanger.gz
	SRR11973429_2.fastq.gz	Fastqsanger.gz
	SRR11973430_1.fastq.gz	Fastqsanger.gz

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Transcriptomic Response of Brain Tissue to Focused Ultrasound-Mediated Blood-Brain Barrier Disruption Depends Strongly on Anesthesia - Bulk RNA-seq

Project description:Focused ultrasound (FUS) mediated blood brain barrier disruption (BBBD) is a promising strategy for the targeted delivery of systemically-administered therapeutics to the central nervous system (CNS). Pre-clinical investigations of BBBD have been performed on different anesthetic backgrounds; however, the potential influence of the choice of anesthetic on the molecular response to BBBD is unknown, despite its potential to critically affect interpretation of experimental therapeutic outcomes. Here, using bulk RNA sequencing approaches, we comprehensively examined the transcriptomic response of both normal brain tissue and brain tissue exposed to FUS-induced BBBD in mice anesthetized with either Isoflurane with medical air (Iso) or Ketamine/Dexmedetomidine (KD). In normal murine brain tissue, Iso alone elicited minimal differential gene expression (DGE) and repressed pathways associated with neuronal signaling. KD alone, however, led to massive DGE and enrichment of pathways associated with protein synthesis. In brain tissue exposed to BBBD (1 MHz, 0.5 Hz pulse repetition frequency, 0.4 MPa peak-negative pressure), we systematically evaluated the relative effects of anesthesia, microbubbles, and FUS on the transcriptome. Of particular interest, we observed that gene sets associated with sterile inflammatory responses and cell-cell junctional activity were induced by BBBD, regardless of the choice of anesthesia. Meanwhile, gene sets associated with metabolism, platelet activity, tissue repair, and signaling pathways, were differentially affected by BBBD, with a strong dependence on the anesthetic. We conclude that the underlying transcriptomic response to FUS-mediated BBBD may be powerfully influenced by anesthesia. These findings raise considerations for the translation of FUS-BBBD delivery approaches that impact, in particular, metabolism, tissue repair, and intracellular signaling.

2020-06-11 | GSE152171 | GEO

Single-cell sequencing of brain macrophages after focused-ultrasound blood-brain barrier opening

Project description:Single-cell sequencing of brain macrophages after focused-ultrasound blood-brain barrier opening

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Single-cell sequencing of brain macrophages after focused-ultrasound blood-brain barrier opening

Project description:Focused Ultrasound (FUS) combined with microbubbles (FUS+MB) to transiently open the blood brain barrier (BBB) has shown promise as an immunotherapeutic in models of neurodegenerative disorders - resulting in significantly reduced pathological load and improved cognition. Preliminary histology and bulk tissue analysis of FUS+MB have indicated brain macrophage changes as a potential mechanism of the immunotherapy. However, prior to this study the temporal effect of FUS+MB on the two dominant brain macrophage populations - microglia and central nervous system associated macrophages (CAM) has not been reported. In this study, we establish that FUS+MB triggers a biphasic process involving both microglia and CAM. In the Phase I, 24h after treatment, microglia and resident CAM exhibit an early response signature, characterized by the upregulation of recruitment-associated chemokine and cytokines. In Phase II, 72h after treatment, CAM population size increases dramatically and both cell types exhibit a late response signature, characterized by upregulation of interferon genes indicative of cellular activation and immune response. Next, cell cycle analysis and immunohistochemistry indicate that microglia exhibit increased proliferation across both phases but CAM do not. Finally, the brain macrophage population size is correlated with the ultrasound-induced cavitation dose, indicating a dose-dependent response to treatment. The findings presented herein not only provide insight into the mechanism of the FUS+MB immunomodulatory effects but also into a mechanism of brain macrophage response that is capable of ameliorating neurological disease.

2023-06-17 | GSE198707 | GEO

Microarray analysis of rat hippocampal microvessels at acute time points following focused ultrasound-induced increase in blood-brain barrier permeability

Project description:Therapeutic treatment options for central nervous system diseases are greatly limited by the blood-brain barrier (BBB). Focused ultrasound (FUS), in conjunction with circulating microbubbles, can be used to induce a targeted and transient increase in BBB permeability, providing a unique approach for the delivery of drugs from the systemic circulation into the brain. While preclinical research has demonstrated the utility of FUS, there remains a large gap in our knowledge regarding the impact of sonication on BBB gene expression. This work is focused on investigating the transcriptional changes in dorsal hippocampal rat microvessels in the acute stages following sonication. Microarray analysis of microvessels was performed at 6 and 24 hrs post-FUS. Microvessels were collected by laser capture microdissection. Relative gene expression was compared between samples collected from the sonicated hemisphere and samples collected from the hemisphere contralateral to sonication, as well as samples collected from rats not undergoing the FUS procedure.

2017-09-01 | E-MTAB-5251 | biostudies-arrayexpress

Transcriptomic response of brain tissue to focused ultrasound-mediated blood-brain barrier disruption depends strongly on anesthesia.

Project description:Focused ultrasound (FUS) mediated blood-brain barrier disruption (BBBD) targets the delivery of systemically-administered therapeutics to the central nervous system. Preclinical investigations of BBBD have been performed on different anesthetic backgrounds; however, the influence of the choice of anesthetic on the molecular response to BBBD is unknown, despite its potential to critically affect interpretation of experimental therapeutic outcomes. Here, using bulk RNA sequencing, we comprehensively examined the transcriptomic response of both normal brain tissue and brain tissue exposed to FUS-induced BBBD in mice anesthetized with either isoflurane with medical air (Iso) or ketamine/dexmedetomidine (KD). In normal murine brain tissue, Iso alone elicited minimal differential gene expression (DGE) and repressed pathways associated with neuronal signaling. KD alone, however, led to massive DGE and enrichment of pathways associated with protein synthesis. In brain tissue exposed to BBBD (1 MHz, 0.5 Hz pulse repetition frequency, 0.4 MPa peak-negative pressure), we systematically evaluated the relative effects of anesthesia, microbubbles, and FUS on the transcriptome. Of particular interest, we observed that gene sets associated with sterile inflammatory responses and cell-cell junctional activity were induced by BBBD, regardless of the choice of anesthesia. Meanwhile, gene sets associated with metabolism, platelet activity, tissue repair, and signaling pathways, were differentially affected by BBBD, with a strong dependence on the anesthetic. We conclude that the underlying transcriptomic response to FUS-mediated BBBD may be powerfully influenced by anesthesia. These findings raise considerations for the translation of FUS-BBBD delivery approaches that impact, in particular, metabolism, tissue repair, and intracellular signaling.

| S-EPMC8126816 | biostudies-literature

Transcriptomic profiling of diabetic rats treated with peripherical focused ultrasound (pFUS)

Project description:Transcriptomic profiling of diabetic rats treated with peripherical focused ultrasound (pFUS)

| PRJNA808966 | ENA

Spatiotemporal local and abscopal cell death and immune responses to histotripsy focused ultrasound tumor ablation

Project description:Histotripsy is a novel focused ultrasound tumor ablation modality with potent immunostimulatory effects. To measure the spatiotemporal kinetics of local and abscopal responses to histotripsy, C57BL/6 mice bearing bilateral flank B16 melanoma or Hepa1-6 hepatocellular carcinoma tumors were treated with unilateral sham or partial histotripsy. Treated and Controltralateral untreated (abscopal) tumors were analyzed using multicolor immunofluorescence, digital spatial profiling, RNA sequencing (RNASeq), and flow cytometry.

2023-01-12 | GSE221448 | GEO

Transcriptional Reprogramming of Brain Cells Under Anesthesia in wt and Alzheimer's Disease mouse model

Project description:In this study, we addressed the following questions: Which brain cell types are transcriptionally reprogrammed under anesthesia? What is the cell-type specific response to anesthesia? And how does the response change between WT and AD in mouse models? We profiled by single nucleus RNA-sequencing (snRNA-seq) of hippocampus brain region samples from awake and anesthetized wild-type (WT) and APP/PS1 AD mouse model. We found a strong and robust transcriptional switch in all glial cell types in the anesthetized mice and in specific neuronal sub-types. Comparing WT to AD mice uncovered an AD-specific transcriptional response to anesthesia in glial cells and in specific neuronal sub-types. These findings provide new insights on the molecular changes occurring in the anesthetized brain and how they are altered in AD.

2023-10-19 | GSE245201 | GEO

Expression data from sevoflurane anesthesia treated rat

Project description:Long noncoding RNAs (lncRNAs) play important roles in brain function modulation and neurodegenerative diseases. However, whether lncRNA regulations are involved in the mechanisms of perioperative neurocognitive disorders (PNCD), especially in anesthesia related brain dysfunction, remains unknown. We explored the expression and regulation pattern profiles of lncRNAs in the hippocampus of aged rats after sevoflurane anesthesia with microarrays.

2020-12-29 | GSE139220 | GEO

Multiple regression analysis of a comprehensive transcriptomic data assembly elucidates mechanically- and biochemically-driven responses to focused ultrasound blood-brain barrier disruption - additional non-FUS controls

Project description:Focused ultrasound (FUS) blood brain barrier disruption (BBBD) permits the noninvasive, targeted, and repeatable delivery of drugs to the brain. FUS BBBD also elicits secondary responses capable of augmenting immunotherapies, clearing amyloid-β and hyperphosphorylated tau, and driving neurogenesis. Leveraging these secondary effects will benefit from an understanding of how they correlate to the magnitude of FUS BBBD and are differentially affected by the mechanical and biochemical stimuli imparted during FUS BBBD. Microbubble activation (MBA) and contrast enhancement (CE) differentially predicted expression of 1,124 genes 6 h or 24 h later. While there existed overlap in the transcripts correlated with MBA vs CE, MBA was principally predictive of expression of genes associated with endothelial reactivity while CE chiefly predicted sterile inflammation gene sets. Over-representation analysis identified transcripts not previously linked to BBBD, including actin filament organization, which is likely important for BBB recovery. Transcripts and pathways associated with neurogenesis, microglial activation, and amyloid-β clearance were significantly correlated to BBBD metrics. This submission includes non-FUS controls to supplement other studies analyzed within the work (GSE152171, GSE141728).

2021-09-27 | GSE184751 | GEO

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