Journal ArticleDOI
Neuroprotective Effect of Cilostazol against Focal Cerebral Ischemia via Antiapoptotic Action in Rats
TLDR
Cilostazol treatment decreases ischemic brain infarction in association with inhibition of apoptotic and oxidative cell death and reduces the size of infarcts produced by subjecting rats to 2-h occlusion of the left middle cerebral artery followed by 24-h reperfusion.Abstract:
This study examined the protective effects of cilostazol on cerebral infarcts produced by subjecting rats to 2-h occlusion of the left middle cerebral artery followed by 24-h reperfusion. The ischemic cerebral infarct consistently involved the cortex and striatum. The infarct size was significantly reduced, when rats received 10 mg/kg cilostazol intravenously 5 min or 1 h after the completion of 2-h ischemia. Cyclic AMP level was significantly elevated in the cortex of 4- and 12-h reperfusion (P < 0.01) following treatment with cilostazol (10 mg/kg, 5 min after 2-h ischemia) accompanied by decreased tumor necrosis factor-alpha level. Samples from the regions corresponding to the penumbra showed markedly reduced Bcl-2 protein level and, in contrast, high levels of Bax protein and cytochrome c release. Cilostazol decreased Bax protein and cytochrome c release and increased the levels of Bcl-2 protein. Cilostazol (10(-7)-10(-5) M) potently and concentration dependently scavenged hydroxyl and peroxyl radicals. In conclusion, cilostazol treatment decreases ischemic brain infarction in association with inhibition of apoptotic and oxidative cell death.read more
Citations
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Matrix metalloproteinases and blood-brain barrier disruption in acute ischemic stroke.
TL;DR: The role of matrix metalloproteinases (MMPs) in blood-brain barrier (BBB) disruption as a consequence of ischemic stroke is discussed and MMP-9 in particular appears to play an important role in tPA-associated hemorrhagic complications.
Journal ArticleDOI
Cerebral hypoperfusion and glucose hypometabolism: Key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer's disease.
TL;DR: The importance of treating comorbid disease conditions to attenuate inflammation and ONS and ameliorate decreased cerebral blood flow and hypometabolism is underscored.
Journal ArticleDOI
Molecular Mechanisms of Apoptosis in Cerebral Ischemia: Multiple Neuroprotective Opportunities
TL;DR: This review briefly focuses I/R injury-induced multiple mechanisms of apoptosis, involving key apoptotic regulators and their emerging roles in orchestrating cell death programme and the role of autophagy in modulating cell survival/death during cerebral ischemia.
Journal ArticleDOI
Exendin-4, a glucagon-like peptide-1 receptor agonist, provides neuroprotection in mice transient focal cerebral ischemia.
Shinichiro Teramoto,Nobukazu Miyamoto,Kenji Yatomi,Yasutaka Tanaka,Hidenori Oishi,Hajime Arai,Nobutaka Hattori,Takao Urabe +7 more
TL;DR: It is suggested that exendin-4 provides neuroprotection against ischemic injury and that this action is probably mediated through increased intracellular cAMP levels.
Journal ArticleDOI
Cilostazol Protects Against Brain White Matter Damage and Cognitive Impairment in a Rat Model of Chronic Cerebral Hypoperfusion
TL;DR: It is suggested that cilostazol is potentially useful for the treatment of cognitive impairment in poststroke patients and exerts a brain-protective effect through the CREB phosphorylation pathway leading to upregulation of Bcl-2 and COX-2 expressions.
References
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Bax directly induces release of cytochrome c from isolated mitochondria
Juliane M. Jürgensmeier,Zhihua Xie,Quinn Deveraux,Lisa M. Ellerby,Dale E. Bredesen,John C. Reed +5 more
TL;DR: It is shown that addition of submicromolar amounts of recombinant Bax protein to isolated mitochondria can induce cytochrome c (Cyt c) release, whereas a peptide representing the Bax BH3 domain was inactive, implying that Bax uses an alternative mechanism for triggering release of Cyt c from mitochondria.