lncRNA DHFRL1‑4 knockdown attenuates cerebral ischemia/reperfusion injury by upregulating the levels of angiogenesis‑related genes.

The present study aimed to investigate the effects of long non‑coding (lncRNA) dihydrofolate reductase‑like 1 (DHFRL1‑4) on cerebral ischemia/reperfusion (I/R)‑induced injury. For this purpose, mice injected with lentivirus with small interfering RNA targeting DHFRL1‑4 or negative control siRNA were used to construct models of cerebral I/R injury. Following the establishment of the model, the infarct size, neurological deficit score, apoptosis and the expression levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), Wnt family member 3a (Wnt3a), glycogen synthase kinase‑3β (GSK‑3β) and phosphorylated GSK‑3β were assessed. The expression of DHFRL1‑4 was significantly upregulated in the I/R model. In the control and sham groups, the boundaries between the cortex and gray matter were clear, and no edema or necrosis were observed. The nerve cells were arranged orderly and evenly, and the cell membranes were intact with visible nucleus and nucleolus. In the model group however, the nerve fibers were slightly necrotic and swollen, and the number of nerve cells was reduced. In the mice injected with si‑DHFRL1‑4 lentivirus, the brain tissues exhibited less liquefaction and degeneration, as well as less edema. Compared with the control and sham groups, the model group had a significantly larger infarct area, a higher apoptotic rate, higher bFGF, VEGF, Wnt3a and GSK‑3β expression levels and a greater neurological deficit score. However, the mice injected with si‑DHFRL1‑4 lentivirus exhibited a significantly reduced infarct area, a lower apoptotic rate, lower Wnt3a and GSK‑3β expression levels, a lower neurological deficit score, and significantly upregulated bFGF and VEGF levels.