The Time Sequence of Gene Expression Changes after Spinal Cord Injury

Abstract

Gene expression changes following spinal cord injury (SCI) are time-dependent, and an accurate understanding of these changes can be crucial in determining time-based treatment options in a clinical setting. We performed RNA sequencing of the contused spinal cord of rats at five different time points from the very acute to chronic stages (1 hour, 1 day, 1 week, 1 month, and 3 months) following SCI. We identified differentially expressed genes (DEGs) and Gene Ontology (GO) terms at each time point, and 14,257 genes were commonly expressed at all time points. The biological process of the inflammatory response was increased at 1 hour and 1 day, and the cellular component of the integral component of the synaptic membrane was increased at 1 day. DEGs associated with cell activation and the innate immune response were highly enriched at 1 week and 1 month, respectively. A total of 2841 DEGs were differentially expressed at any of the five time points, and 18 genes (17 upregulated and 1 downregulated) showed common expression differences at all time points. We found that interleukin signaling, neutrophil degranulation, eukaryotic translation, collagen degradation, LGI–ADAM interactions, GABA receptor, and L1CAM-ankyrin interactions were prominent after SCI depending on the time post injury. We also performed gene–drug network analysis and found several potential antagonists and agonists which can be used to treat SCI. We expect to discover effective treatments in the clinical field through further studies revealing the efficacy and safety of potential drugs.

Immune Status of Individuals with Traumatic Spinal Cord Injury: A Systematic Review and Meta-Analysis

“…This indicates that the injury induces an immune response that is directed to the lesion that may be facilitated by multiple cytokines at the acute-subacute phase [1,4,14,15,[36][37][38]. This interplay of pro-and anti-inflammatory cytokines and immune cell migration at the acute-subacute phase is likewise seen in gene expression studies [39,40]. The control of these initial immune-inflammatory processes may help improve the neurologic recovery [5,11,13,41], and recent studies look into the utility of neutrophil to lymphocyte ratio as a predictor for this recovery [14,42,43].…”

Gene expression and locomotor recovery in adult rats with spinal cord injury and plasma-synthesized polypyrrole/iodine application combined with a mixed rehabilitation scheme

“…Other studies have shown a continued decrease in the gene expression of members of the ADAM family that affects neuronal plasticity at the chronic stage of SCI ( 84 ). In animals from the PPy/I group, an upregulated expression of ADAM8, a member of ADAM's family, was observed.…”

“…It had also been reported about significant alterations in SLC17A7 (VGLUT1) expression from 1 h to 3 months after SCI (84). SLC17A7 belongs to a big family of sialic acid proteins that are known to play an important role in absorbing glutamate into synaptic vesicles at presynaptic nerve terminals and excitatory neurons (85-87).…”

Sexual Dimorphism of Spinal Neural Circuits Controlling the Mouse External Urethral Sphincter With and Without Spinal Cord Injury

“…Most studies of EUS/EAS-MNs in mammals have been done in cats and rats (Takahashi et al 2013;Thor and de Groat 2010;Muramatsu et al 2008;Sasaki 1991Sasaki , 1994), but it is not possible in these animals to use techniques employing genetically modified specific cell types in order to uncover details of circuit organization and dynamic post-SCI changes at the molecular level. Therefore, in recent years, SCI studies have been conducted in mice to utilize these methods (Kadekawa et al 2016(Kadekawa et al , 2017Keller et al 2018;Mun et al 2022;Yuan et al 2022;Liu et al 2022). In this article, we used transgenic ChAT-GFP mice expressing green fluorescent protein in cholinergic neurons to visualize all available MNs and reveal their fate after SCI.…”