Abstract
Cerebral ischemia‑reperfusion injury (CIRI) is associated with high morbidity and mortality rates and its pathogenesis is complex. Phosphodiesterase 2 (PDE2) has been proposed to exert a protective effect, although, to the to the best of the authors' knowledge, its role in CIRI has yet to be reported. Therefore, the aim of the present study was to investigate the role of PDE2 in CIRI. To meet this aim, a middle cerebral artery occlusion (MCAO) model was established in mice. After having successfully modeled the MCAO, the mice were treated with the PDE2 inhibitor Bay‑607550 and the expression level of PDE2 was detected using reverse transcription‑quantitative (RT‑q) PCR and western blot analysis. Histopathology of the brain was assessed using hematoxylin and eosin staining. The proportions of dry and wet tissue in brain were recorded and the cerebral ischemia area was assessed using 2,3,5‑triphenyltetrazolium chloride staining. RT‑qPCR was also used to measure the expression levels of inflammatory factors. The expression of ionized calcium binding adaptor molecule 1, a marker of microglia activation, was detected by immunofluorescence assay, western blotting and RT‑qPCR. Western blotting was used to detect the expression levels of P65 and NF‑κB inhibitor α and their phosphorylated forms. The levels of apoptosis were subsequently determined using TUNEL and western blot analysis. SH‑SY5Y cells were induced by oxygen‑glucose deprivation (OGD) and the expression levels of PDE2 were subsequently detected. Cell transfection was used to interfere with the expression of PDE2 and the regulation of PDE2 upon OGD/reoxygenation (OGD/R)‑induced inflammation and apoptosis was further detected in cell experiments. Finally, western blot analysis was used to detect the expression of protein kinase A (PKA) downstream of PDE2 in vivo and in vitro. The expression levels of PDE2 were found to be significantly increased in the MCAO model mice. Following treatment with Bay‑607550, the condition of the brain nerve cells was improved with respect to the levels of cerebral ischemia, inflammation and apoptosis. The results of the in vitro cell experiments were found to be consistent with those of the in vivo animal experiments. Furthermore, the western blotting experiments suggested that the above‑mentioned regulation of PDE2 may be achieved via regulating PKA. Taken together, the present study has shown that inhibition of PDE2 led to a reduction in inflammation and apoptosis during CIRI through regulating PKA.