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Cyclosporine A Accelerates Neurorecovery Transcriptional Trajectory in a Swine Model of Diffuse Traumatic Brain Injury

ABSTRACT: Cyclosporine A Accelerates Neurorecovery Transcriptional Trajectory in a Swine Model of Diffuse Traumatic Brain Injury

PROVIDER: PRJNA1147761 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30227400_1.fastq.gz	Fastqsanger.gz
	SRR30227400_2.fastq.gz	Fastqsanger.gz
	SRR30227500_1.fastq.gz	Fastqsanger.gz
	SRR30227500_2.fastq.gz	Fastqsanger.gz
	SRR30227600_1.fastq.gz	Fastqsanger.gz

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Cyclosporine A Accelerates Neurorecovery Transcriptional Trajectory in a Swine Model of Diffuse Traumatic Brain Injury

Project description:Mild traumatic brain injury (mTBI) is a leading cause of morbidity in children with both short and long-term neurological, cognitive, cerebrovascular, and emotional deficits. Given limited understanding of the transcriptional changes associated with its pathophysiological cascades, we studied formalin fixed paraffin embedded (FFPE) tissues from the frontal cortex (FC) and the hippocampus + amygdala (HA) regions of swine (N=40) after a sagittal rapid non-impact head rotation (RNR). We then sequenced RNA to define transcriptional changes at 1 day and 1 week after injury and investigated the protective influence of cyclosporine A (CsA) treatment. Differentially expressed genes (DEGs) were classified into 5 temporal patterns (Early, Transient, Persistent, Intensified, Delayed, or Late), and were more abundant at 1 week than 1 day. Shared significant gene ontology annotations in both regions included terms associated with neuronal distress at 1 day and neurorecovery at 1 week. CsA (20mg/kg/day) infused for 1 day, (beginning at 6 hours after injury) accelerated 466 DEGs in the FC and 2794 DEGs in the HA, such that the CsA treated transcriptional profile were associated with neurorecovery. Overall, our data reveals the effects of anatomic region and elapsed time on gene expression post-mTBI and motivates future studies of CsA treatment.

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Cyclosporine on fibroblast

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Spatiotemporal trajectory analysis and validation of microglia activation in traumatic brain injury

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Cyclosporine on fibroblast

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Project description:Spatial transcriptomics (ST) is an innovative technology that holds tremendous potential for transforming the field of tissue biology research. By simultaneously capturing multiple types of spatial data, including gene expression values, spatial distance information, and tissue morphology, ST enables a comprehensive understanding of biological samples. However, the effective integration of these diverse data types remains a challenge. In this study, we present stLearn, a collection of three computational-statistical algorithms specifically designed to exploit the combined power of gene expression, spatial distance, and tissue morphology data. Our aim is to unlock novel insights into tissue maintenance, development, and disease. The first algorithm, known as pseudo-time-space (PSTS), employs a spatial-graph-based approach to uncover the spatial relationships between cells' transcriptional states in dynamic tissue contexts. To demonstrate the effectiveness of stLearn, we utilize traumatic brain injury datasets to investigate the spatio-temporal dynamics of microglia activation. By applying the PSTS algorithm to a well-established mouse model of acquired brain injury, we successfully reconstruct the spatial trajectory of microglia activation following insult, thereby validating this key component of stLearn.

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