Secondary single-cell transcriptomic analysis reveals common molecular signatures of cerebrovascular injury between traumatic brain injury and aging

Abstract

<jats:title>Abstract</jats:title><jats:p>Cerebrovascular injury is a common pathological feature of a spectrum of neurological disorders including traumatic brain injury (TBI), stroke, Alzheimer’s disease (AD), as well as aging. Vascular manifestations among these conditions are similar indeed, including the breakdown of the blood-brain barrier (BBB). However, whether there is a common molecular mechanism underlying the vascular changes among these conditions remains elusive. Here, we report secondary transcriptomic analysis on cerebrovascular cells based single-cell RNA-seq datasets of mouse models of mild TBI and aging, with a focus on endothelial cells and pericytes. We identify several molecular signatures commonly found between mTBI and aging vasculature, including <jats:italic>Adamts1, Rpl23a, Tmem252, Car4, Serpine2</jats:italic>, and <jats:italic>Ndnf</jats:italic> in endothelial cells, and <jats:italic>Rps29</jats:italic> and <jats:italic>Sepp1</jats:italic> in pericytes. These markers may represent the shared endophenotype of microvascular injury and be considered as cerebrovascular injury responsive genes. Additionally, pathway analysis on differentially expressed genes demonstrated alterations in common pathways between mTBI and aging, including vascular development and extracellular matrix pathways in endothelial cells. Hence, our analysis suggests that cerebrovascular injury triggered by different neurological conditions may share common molecular signatures, which may only be detected at the single-cell transcriptome level.</jats:p>

Transcriptional Pathology Evolves Over Time in Rat Hippocampus Following Lateral Fluid Percussion Traumatic Brain Injury

“…Our data demonstrate the power of time course evaluations to chart the course of transcriptomic sequalae caused by experimental TBI. Our findings recapitulate several previously published observations 5,8,11,12,37 . Of note, the signatures identified here differ substantially between the genes that are induced (i.e.…”

“…Measurement of the perturbations in gene expression in bulk tissue and single cells following TBI in model systems has provided a systems-level perspective of the impacts of TBI [8][9][10][11][12] . In the initial period following TBI, transcriptional studies have identified signatures of neuroinflammation, and cell death, that correlate with long-term outcomes such as cognitive dysfunction.…”