title: Neuroprotective effects of penehyclidine hydrochloride against cerebral ischemia/reperfusion injury in mice.
abstract: 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 (0.1mg/kg) group, and I/R+PHC (1mg/kg) group. Mice were subjected to 2h of transient middle cerebral artery occlusion, followed by 24h 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.
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, China; Department of Pain Treatment Pain Management, First Affiliated Hospital of Xi'an Medical University, Xi'an, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Shu
authors.affiliation: The Second Department of Orthopedics, Xi'an Central Hospital, Xi'an, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, China. Electronic address: neuro0123@sina.com.
authors.forename: Pengbo
authors.initials: P
authors.lastname: Zhang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D020520:Brain Infarction / Q000188:drug therapy / Q000209:etiology; D002199:Capillary Permeability / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005979:Glutathione Peroxidase; D020287:In Situ Nick-End Labeling; D008297:Male; D008315:Malondialdehyde; D051379:Mice; D008810:Mice, Inbred C57BL; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011812:Quinuclidines / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D013482:Superoxide Dismutase; D013997:Time Factors
chemical_list: D016207:Cytokines; D018696:Neuroprotective Agents; D011812:Quinuclidines; C486140:penehyclidine; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
keywords: Cerebral ischemia/reperfusion injury; JNK/p38MAPK; Penehyclidine hydrochloride