Ac-YVAD-CMK Decreases Blood-Brain Barrier Degradation by Inhibiting Caspase-1 Activation of Interleukin-1 beta in Intracerebral Hemorrhage Mouse Model

作者：Wu Bihua; Ma Qingyi; Khatibi Nikan; Chen Wanqiu; Sozen Takumi; Cheng Oumei; Tang Jiping^*

来源：Translational Stroke Research, 2010, 1(1): 57-64.

DOI：10.1007/s12975-009-0002-z

• Collagenase
• Intracerebral hemorrhage
• Edema
• IL-1 beta

Among many proinflammatory cytokines, interleukin-1 beta (IL-1 beta) is considered a key mediator of neuronal injury. However, in order to become activated, it must be processed and cleaved by a caspase-1 enzyme. In this study, we tested the neuroprotective effect of Ac-YVAD-CMK, a known selective caspase-1 inhibitor, in a mouse model of intracerebral hemorrhage (ICH). Sixty-six adult male CD-1 mice were subjected to collagenase-induced ICH. Ac-YVAD-CMK or vehicle was administered into the left lateral ventricle 20 min before ICH modeling. Brain edema and neurological functions were assessed at 24 and 72 h after the surgery. Expression of IL-1 beta, phosphorylated JNK, tight junction protein zona occludens 1 (ZO-1), and matrix metalloproteinase-9 (MMP-9) were measured by Western blot along with MMP-9 activity measured by zymography at 24 h after ICH. At 24 h after ICH, Ac-YVAD-CMK treatment significantly reduced brain edema and improved neurological functions. The neuroprotection was associated with downregulation of IL-1 beta, JNK, MMP-9, and an inhibition of ZO-1 degradation in brain. We conclude that Ac-YVAD-CMK protects the brain against ICH-induced injury, and the neuroprotective effect may result from anti-inflammation-induced blood-brain barrier protection.

• 出版日期2010-3
• 单位川北医学院