کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4318666 | 1613235 | 2016 | 9 صفحه PDF | دانلود رایگان |
• PHC protects against cerebral I/R injury.
• PHC improved neurological deficits and reduced cerebral infarct volume after cerebral I/R injury.
• PHC alleviates apoptosis, inflammation, and oxidative stress after cerebral I/R injury.
• PHC inhibited the JNK/p38MAPK pathway after cerebral I/R injury.
Various reports have suggested that penehyclidine hydrochloride (PHC), a new cholinergic antagonist, exhibits a variety of biological actions such as anti-tumor and cardioprotective effects. This study aimed to investigate the effects of PHC on cerebral ischemia/reperfusion (I/R) injury and evaluate whether the c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (p38MAPK) pathway is involved in the protective effects of PHC. Male C57BL/6 mice were randomly assigned to Sham group, ischemia/reperfusion (I/R) group, I/R + PHC (0.1 mg/kg) group, and I/R + PHC (1 mg/kg) group. Mice were subjected to 2 h of transient middle cerebral artery occlusion, followed by 24 h of reperfusion except the mice in the sham group. Neurological deficits, infarct volume, brain water content, blood–brain barrier (BBB) integrity, and neuronal apoptosis were evaluated. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), superoxide production, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were measured. The expressions of the key proteins in the JNK/p38MAPK pathway were detected using the Western blot. The results suggested that compared to the I/R group, the PHC-treated group showed improved neurological deficits and BBB integrity, and reduced infarction volume, brain water content, and apoptosis. In addition, PHC significantly suppressed the levels of TNF-α, IL-1β, superoxide production, and MDA, and increased the levels of SOD and GSH-Px. Finally, PHC significantly downregulated the phosphorylation of JNK, p38MAPK, and c-Jun, indicating PHC protects against cerebral I/R injury by downregulating the JNK/p38MAPK signaling pathway.
Journal: Brain Research Bulletin - Volume 121, March 2016, Pages 115–123