Backgrounds: MicroRNAs (miRNAs) play important roles in the regulation of gene expression at the post-transcriptional level. Furthermore, in various human disease, miRNAs have been identified as potential biomarkers. However, it remains to be elucidated whether and how miRNAs play roles in the development of cerebral vasospasm (CVS) or delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). The purposes of this study are to detect differential miRNAs in cerebrospinal fluid (CSF) and serum in SAH patients and to identify possible miRNAs involved in the mechanisms of the vascular proliferation or phenotypic changes after SAH.
Methods: The CSF and serum samples were taken every other day for 2 weeks after SAH in patients with endovascular aneurysm repair. Microarray analysis of exosomal miRNA from samples was performed using 3D-Gene miRNA labeling kit (Toray). The temporal changes in the expression of differentially expressed miRNAs in early phase after SAH and its associated molecules were evaluated using quantitative RT-PCR.
Results: Among over 2500 miRNAs screened out, microarray analysis revealed 12 diffrentially expressed genes which were up- and/or down-regulated (FC>2-fold) both in the CSF and serum during early phase after SAH. RT-PCR analysis revealed that miRNAs involving vascular angiogenesis were up-regulated on day3 in serum and day5 in CSF. Contrarily, RT-PCR also revealed mRNAs of those associated molecules which exert anti-angiogenic and anti-proliferative effects were down-regulated on day1 in CSF and day3 in serum. These results suggest that these miRNAs expressions are controlled by negative-feedback regulation of associated molecules participating in maintaining vascular homeostasis.
Conclusion: Our present study indicates that some miRNAs and molecules may be involved in vascular proliferation or angiogenesis by interacting each other after SAH.