Affiliations 

  • 1 Faculty of Reproductive Health, Golestan University of Medical Sciences, Gorgan, Iran
  • 2 Faculty of Medicine, Department of Cellular and Molecular Medicine, Royal's Institute of Mental Health Research, University of Ottawa, Ottawa, Canada
  • 3 Department of Medical Veterinary, Azad University, Garmsar Branch, Garmsar, Iran
  • 4 Department of Hematology, School of Allied Health, Iran University of Medical Sciences, Tehran, Iran
  • 5 Department of Basic Sciences, Asadabad School of Medical Sciences, Asadabad, Iran
  • 6 Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 Serdang, Selangor Darul Ehsan, Malaysia
  • 7 Department of Midwifery & Reproductive Health, Faculty of Medical Sciences, Tarbiat Modares University, Jalal Ale Ahmad Highway, Tehran, Iran
Curr Med Chem, 2023 Sep 15.
PMID: 37724672 DOI: 10.2174/0929867331666230915103147

Abstract

BACKGROUND: Epilepsy and intraventricular-cerebral hemorrhage is a common complication irreversible in preterm infants. Inflammation leads to an increase in intracellular calcium, acidosis, and oxygen usage, and finally, may damage brain cells. Increases in HIF-1a and HVCN1 can reduce the complications of oxygen consumption and acidosis in infants with intraventricular hemorrhage (IVH). On the other hand, decreases in S100B can shield nerve cells from apoptosis and epilepsy by reducing brain damage.

OBJECTIVE: In this research, we investigated how miR-138-siRNAs-HIF-1a and miR-21-siRNAs-HVCN1 affect apoptosis in hypoxic mice.

METHODS: On the first and third days after delivery, the YKL40, HIF-1a, HVCN1, and S100b genes were compared between two groups of preterm infants with and without maternal inflammation. Afterward, the miRNAs were transfected into cell lines to monitor variations in YKL40, HIF-1a, HVCN1, and S100b gene expression and nerve cell apoptosis. We changed the expression of S100b, HVCN1, and HIF-1a genes by using specific siRNAs injected into mice. Using real-time PCR, Western blotting, flow cytometry (FCM), and immunofluorescence, and changes in gene expression were evaluated (IHC).

RESULTS: HVCN1 gene expression showed a strong negative correlation with epilepsy in both groups of infants (P<0.001). Significant correlations between epilepsy and the expression levels of the S100b, YKL40, and HIF-1a genes were found (P<0.001). According to FCM, after transfecting miRNA-431 and miRNA-34a into cell lines, the apoptosis index (A.I.) were 41.6 3.3 and 34.5 5.2%, respectively, while the A.I. were 9.6 2.7 and 7.1 4.2% after transfecting miRNA-21 and miRNA-138. MiR-138-siRNAs-HIF-1a and miR-21-siRNAs-HVCN1 were simultaneously injected into hypoxic mice, and IHC double-labeling revealed that this reduced apoptosis and seizures compared to the hypoxic group.

CONCLUSION: Our findings demonstrate that miR-138-siRNAs-HIF-1a and miR-21-siRNAs-HVCN1 injections prevent cerebral ischemia-induced brain damage in hypoxia mice by increasing HVCN1 and HIF-1a and decreasing S100b, which in turn lessens apoptosis and epilepsy in hypoxic mice.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.