Circular Ribonucleic Acid Expression Alteration in Exosomes from the Brain Extracellular Space after Traumatic Brain Injury in Mice.

Traumatic brain injury (TBI) has high morbidity and mortality rates. The mechanisms underlying TBI are unclear and may include the change in biological material in exosomes. Circular ribonucleic acids (circRNAs) are enriched and stable in exosomes, which can function as microRNA (miRNA) sponges to regulate gene expression levels. Therefore, we speculated that circRNAs in exosomes might play an important role in regulating gene expression after TBI and then regulate specific signaling pathways, which may protect the brain. We first isolated exosomes from the brain extracellular space in mice with TBI by digestion. We then investigated the alterations in circRNA expression in exosomes by high-throughput whole transcriptome sequencing, analyzed the data by gene ontology (GO) and pathway analysis, and constructed the circRNA-miRNA network. In this study, we identified 231 significantly and differentially expressed circRNAs, including 155 that were upregulated and 76 that were downregulated. GO analysis showed that these differentially expressed circRNAs might be related to the growth and repair of neurons, the development of the nervous system, and the transmission of nerve signals. The most highly correlated pathways that we identified were involved primarily with glutamatergic synapse and the cyclic guanosine monophosphate-protein kinase G signaling pathway. The circRNA-miRNA network predicted the potential roles of these differentially expressed circRNAs and the interaction of circRNAs with miRNAs. Our study broadens the horizon of research on gene regulation in exosomes from the brain extracellular space after TBI and provides novel targets for further research on both the molecular mechanisms of TBI and the potential intervention therapy targets.

Electrical stimulation improved cognitive deficits associated with traumatic brain injury in rats.

Introduction: Cognitive deficits associated with traumatic brain injury (TBI) reduce patient quality of life. However, to date, there have been no effective treatments for TBI-associated cognitive deficits. In this study, we aimed to determine whether electrical stimulation (ES) improves cognitive deficits in TBI rats. Methods: Rats were randomly divided into three groups: the Sham control group, electrical stimulation group (ES group), and No electrical stimulation control group (N-ES group). Following fluid percussion injury, the rats in the ES group received ES treatment for 3 weeks. Potent cognitive function-relevant factors, including the escape latency, time percentage in the goal quadrant, and numbers of CD34+ cells, von Willebrand Factor+ (vWF +) vessels, and circulating endothelial progenitor cells (EPCs), were subsequently assessed using the Morris water maze (MWM) test, immunohistochemical staining, and flow cytometry. Results: Compared with the rats in the N-ES group, the rats in the ES group exhibited a shorter escape latency on day 3 (p = .025), day 4 (p = .011), and day 5 (p = .003), as well as a higher time percentage in the goal quadrant (p = .025) in the MWM test. After 3 weeks of ES, there were increased numbers of CD34+ cells (p = .008) and vWF + vessels (p = .000) in the hippocampus of injured brain tissue in the ES group compared with those in the N-ES group. Moreover, ES also significantly increased the number of EPCs in the peripheral blood from days 3 to 21 after TBI in the ES group (p < .05). Conclusions: Taken together, these findings suggest that ES may improve cognitive deficits induced by TBI, and this protective effect may be a result, in part, of enhanced angiogenesis, which may be attributed to the increased mobilization of EPCs in peripheral blood.