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.
journal_name
Brain Res Bulljournal_title
Brain research bulletinauthors
Shu Y,Yang Y,Zhang Pdoi
10.1016/j.brainresbull.2016.01.008subject
Has Abstractpub_date
2016-03-01 00:00:00pages
115-23eissn
0361-9230issn
1873-2747pii
S0361-9230(16)30008-9journal_volume
121pub_type
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journal_title：Brain research bulletin
pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Brain research bulletin
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journal_title：Brain research bulletin
pub_type： 杂志文章,评审
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journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/0361-9230(91)90058-r
更新日期：1991-11-01 00:00:00
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journal_title：Brain research bulletin
pub_type： 杂志文章
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更新日期：2020-12-01 00:00:00
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journal_title：Brain research bulletin
pub_type： 杂志文章
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更新日期：2005-01-30 00:00:00
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pub_type： 杂志文章
doi：10.1016/j.brainresbull.2018.09.010
更新日期：2018-10-01 00:00:00
