title: Ac-YVAD-CMK Decreases Blood-Brain Barrier Degradation by Inhibiting Caspase-1 Activation of Interleukin-1β in Intracerebral Hemorrhage Mouse Model.
abstract: Among many proinflammatory cytokines, interleukin-1β (IL-1β) 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-1β, 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-1β, 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.
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
authors.forename: Bihua
authors.initials: B
authors.lastname: Wu
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Ma
authors.forename: Nikan
authors.initials: N
authors.lastname: Khatibi
authors.forename: Wanqiu
authors.initials: W
authors.lastname: Chen
authors.forename: Takumi
authors.initials: T
authors.lastname: Sozen
authors.forename: Oumei
authors.initials: O
authors.lastname: Cheng
authors.forename: Jiping
authors.initials: J
authors.lastname: Tang