Assessing the Global Impact on the Mouse Kidney After Traumatic Brain Injury: A Transcriptomic Study

Abstract

In this study, we use animal models combined with bioinformatics strategies to investigate the potential changes in overall renal transcriptional expression after traumatic brain injury. Methods: Microarray analysis was performed after kidney acquisition using unilateral controlled cortical impact as the primary mouse TBI model. Multi-oriented gene set enrichment analysis was performed for differentially expressed genes. Results:The results showed that TBI affected the gene set associated with mitochondria function in kidney cells, and a negative enrichment of gene sets associated with immune cell migration and epidermal development was also observed. Analysis of the disease phenotype gene set revealed that differential expression of mitochondria-related genes was associated with lactate metabolism. Alternatively, activation and adhesion of immune cells associated with the complement system may promote autoinflammation in kidney tissue. The simulated immune cell infiltration analysis showed an increase in the proportion of activated memory CD4 T cells and a decrease in the proportion of resting memory CD4 T cells, suggesting that activated memory CD4 T cell infiltration may be involved in the inflammation of renal tissue and cause damage to renal cells, such as principal cells, mesangial cells and loops of Henle cells. Conclusion:This study is the first to reveal the effects of brain trauma on the kidney. TBI may affect the expression of mitochondria function-related gene sets in renal cells by increasing lactate. It may also affect renal mesangial cells by inducing increased infiltration of immune cells through mechanisms related to complement system activation or autoimmune antibodies.

Pulmonary Effects of Traumatic Brain Injury in Mice: A Gene Set Enrichment Analysis

“…In our study, we employed a unilateral controlled cortical impact as the TBI model on adult C57BL/6 male mice, aged 7 weeks, following the methodology adapted from our previous publication [ 29 ]. In brief, the mice were anesthetized with isoflurane and fixed in a stereotaxic frame, with a topical anesthetic applied to the surgical area to reduce discomfort.…”

“…Mouse lung tissues were processed, and total RNA was extracted using TRIzol reagent, following the manufacturer’s guidelines. This methodology was adapted from our previous publication, with modifications for lung tissue analysis, and updated to reflect the use of R version 4.3.2 for subsequent analyses [ 29 ]. For details on monitoring RNA quality, please refer to our previous publication.…”

“…In previous studies carried out by our lab, we observed that TBI affected gene sets related to mitochondrial function in renal cells and saw a negative enrichment in gene sets linked with immune cell migration and epidermal development [ 29 ]. Despite some progress in understanding the pathophysiology of TBI, the mechanisms linking TBI to systemic organ damage, particularly lung damage, remain poorly understood [ 7 , 9 , 27 , 30 , 31 ].…”