Neuroprotective effect of roflumilast under cerebral ischaemia/reperfusion injury in juvenile rats through NLRP‐mediated inflammatory response inhibition

Abstract

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 12th 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‐1β, TNF‐α, 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 β 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.

Magnetic Resonance Images, Pathological Features of Thrombus, and Expression of NLRP Inflammasome in Patients with Acute Ischemic Stroke

“…Endovascular treatment of AIS enables routine pathological examination of cerebral arterial thrombosis. e current studies found that the pathological features of the acute cerebral arterial occlusive thrombus were similar to postmortem pathological examinations [17]. Whether from the heart or arteries, the thrombi have similar structural features and cannot simply be classified as a red or white thrombus.…”

Roflumilast exerted neuroprotective effect in myelin oligodendrocyte glycoprotein35-55 (MOG35-55)-induced experimental autoimmune encephalitis (EAE) model

“…Several groups have demonstrated in vitro neuroprotective activity of roflumilast [29]. Roflumilast has been shown to decrease IL-1β, IL-6, and TNF-α and the number of apoptotic neurons in the brain after subarachnoid hemorrhage (SAH) [9]. Our results are in line with the previous studies that have demonstrated that roflumilast prevents EAE-induced increase in pro-inflammatory induced cytokines.…”

“…Roflumilast was dissolved in Saline: DMSO (98:2, v/v). FTY720 was used as positive control and dissolved in saline [9,39]. Treatment doses of roflumilast and FTY720 were selected according to the previous studies.…”

“…Sema4D, also known as CD100, is the first semaphorin protein that was determined to have immunoregulatory functions and involved in B-cell/dendritic cell activation. As a Class III semaphorin, Sema3A is reported to inhibit immune cell migration [9]. Phosphodiesterases (PDE) are a diverse family of enzymes (with 11 isoforms) responsible for the degradation of cAMP and cGMP.…”

4 hidroksi fenilboronik asidin lipopolisakkarit ile indüklenmiş karaciğer hasarı üzerine muhtemel koruyucu etkilerinin incelenmesi

“…AST seviyeleri incelendiğinde LPS grubundaki AST seviyesinin sağlıklı gruba göre anlamlı şekilde arttığı görülmüştür (p<0,05). Akut veya kronik organ hasarları karaciğerin de dahil olduğu kalp, akciğer, böbrek, pankreas, beyin, gonadlar ve bağırsaklar gibi birçok organda görülebilir [45,[47][48][49]. Karaciğer enfeksiyöz olan veya olmayan birçok ajanla hasara uğrayabilir [50,51].…”