Neuroprotective effect of roflumilast under cerebral ischaemia/reperfusion injury in juvenile rats through NLRP-mediated inflammatory response inhibition
Yükleniyor...
Dosyalar
Tarih
2021
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Wiley
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
This study aims to investigate the protective effect of roflumilast, a phosphodiesterase (PDE)-4 enzyme inhibitor, and demonstrate its possible role in the development prevention of cerebral ischemia/reperfusion injury (CI/RI) after stroke induced by carotid artery ligation in juvenile rats. The rats were randomly divided into five groups: healthy group without any treatment, healthy group administered with 1 mg/kg roflumilast, CI group not administered with roflumilast, CI group administered with 0.5 mg/kg roflumilast, and CI group administered with 1 mg/kg roflumilast. In the CI groups, reperfusion was achieved 2h after ischemia induction; in the roflumilast groups, this drug was intraperitoneally administered immediately after reperfusion and at the 12(th) hour. At the end of 24h, the rats were sacrificed and their brain tissues removed for examination. The mRNA expressions obtained with real-time PCR of IL-1 beta, TNF-alpha, and NLRP3 significantly increased in the CI/RI-induced groups compared with the control group, and this increase was significantly lower in the groups administered with roflumilast compared with the CI/RI-induced groups. Moreover, ELISA revealed that both IL-1 beta and IL-6 brain levels were significantly higher in the CI/RI-induced groups than in the controls. This increase was significantly lower in the groups administered with roflumilast compared with the CI/RI-induced groups. Histopathological studies revealed that the values closest to those of the healthy group were obtained from the roflumilast groups. Nissl staining revealed that the Nissl bodies manifested normal density in the healthy and roflumilast-administered healthy groups, but were rare in the CI/RI-induced groups. Roflumilast treatment increased these decreased Nissl bodies with increasing doses. Observations indicated that the Nissl body density was close to the value in the healthy group in the CI/RI-induced group administered with 1 mg/kg roflumilast. Overall, roflumilast reduced cellular damage caused by CI/RI in juvenile rats, and this effect may be mediated by NLRP3.
Açıklama
Anahtar Kelimeler
cerebral ischaemia, reperfusion injury, IL‐, 1β, IL‐, 6, juvenile rat, NLRP3, roflumilast, stroke, TNF‐, α, Ischemic-Stroke, Risk-Factors, Phosphodiesterase-4 Inhibitor, Reperfusion Injury, Rolipram, Sildenafil, Mechanisms, Children, Therapy, Targets
Kaynak
Clinical and Experimental Pharmacology and Physiology
WoS Q Değeri
Q3
Scopus Q Değeri
Q2
Cilt
48
Sayı
8
