Cilostazol attenuates ischemic brain injury and enhances neurogenesis in the subventricular zone of adult mice after transient focal cerebral ischemia

Tanaka, Yasutaka; Tanaka, Ryota; Liu, M.; Hattori, Nobutaka; Urabe, Takao

doi:10.1016/j.neuroscience.2010.10.008

Cited by 57 publications

(40 citation statements)

References 38 publications

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“…CLS inhibits apoptotic cell death in neurodegenerative disease models such as ischemic stroke and chronic cerebral hypoperfusion [23,36], and helps in the secondary prevention of ischemic stroke [18,24]. CLS also activates a CREB-mediated signaling pathway and enhances the proliferation and differentiation of neuronal progenitor cells [16,37]. …”

Section: Discussionmentioning

confidence: 99%

“…APZ is employed usually as an adjunct therapy in combination with a drug from the group of selective serotonin reuptake inhibitors in the treatment of major depressive disorders [13,14]. Cilostazol (CLS) possesses a powerful means to produce various pleiotropic effects through the elevation of intracellular cyclic adenosine monophosphate (cAMP) levels, resulting in the increased phosphorylation of the cAMP response element binding protein (CREB) [15,16,17]. CLS has been widely approved for the secondary prevention of ischemic stroke [18].…”

Section: Introductionmentioning

confidence: 99%

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Antidepressant Effects of Aripiprazole Augmentation for Cilostazol-Treated Mice Exposed to Chronic Mild Stress after Ischemic Stroke

Kim

Hong

et al. 2017

IJMS

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The aim of this study was to determine the effects and underlying mechanism of aripiprazole (APZ) augmentation for cilostazol (CLS)-treated post-ischemic stroke mice that were exposed to chronic mild stress (CMS). Compared to treatment with either APZ or CLS alone, the combined treatment resulted in a greater reduction in depressive behaviors, including anhedonia, despair-like behaviors, and memory impairments. This treatment also significantly reduced atrophic changes in the striatum, cortex, and midbrain of CMS-treated ischemic mice, and inhibited neuronal cell apoptosis, particularly in the striatum and the dentate gyrus of the hippocampus. Greater proliferation of neuronal progenitor cells was also observed in the ipsilateral striatum of the mice receiving combined treatment compared to mice receiving either drug alone. Phosphorylation of the cyclic adenosine monophosphate response element binding protein (CREB) was increased in the striatum, hippocampus, and midbrain of mice receiving combined treatment compared to treatment with either drug alone, particularly in the neurons of the striatum and hippocampus, and dopaminergic neurons of the midbrain. Our results suggest that APZ may augment the antidepressant effects of CLS via co-regulation of the CREB signaling pathway, resulting in the synergistic enhancement of their neuroprotective effects.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antidepressant Effects of Aripiprazole Augmentation for Cilostazol-Treated Mice Exposed to Chronic Mild Stress after Ischemic Stroke

Kim

Hong

et al. 2017

IJMS

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“…Inhibition of PDEs by montelukast may be beneficial to ischemic neuronal injury, because the resultant accumulation of cAMP protects neurons from ischemic brain injury (Tsukada et al, 2004;Lin et al, 2009) and inhibitors of PDE3 (cilostazol) and PDE4 (rolipram) have protective effects on neurons (Tanaka et al, 2010;Schaal et al, 2012). In addition, its inhibitory effects on P2Y receptors (Mamedova et al, 2005;Pugliese et al, 2009;Lau et al, 2011) may be protective, because downregulation of the novel P2Y-like receptor GPR17 protects from ischemic neuronal injury after focal cerebral ischemia in rats (Ciana et al, 2006;Zhao et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

HAMI 3379, a CysLT₂ Receptor Antagonist, Attenuates Ischemia-Like Neuronal Injury by Inhibiting Microglial Activation

Zhang

Wang

et al. 2013

J Pharmacol Exp Ther

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The cysteinyl leukotrienes (CysLTs) are inflammatory mediators closely associated with neuronal injury after brain ischemia through the activation of their receptors, CysLT1R and CysLT2R. Here we investigated the involvement of both receptors in oxygen-glucose deprivation/recovery (OGD/R)-induced ischemic neuronal injury and the effect of the novel CysLT2R antagonistin comparison with the CysLT1R antagonist montelukast. In primary neurons, neither the nonselective agonist leukotriene D4 (LTD4) nor the CysLT2R agonist N-methyl-leukotriene C4 (NMLTC4) induced neuronal injury, and HAMI 3379 did not affect OGD/R-induced neuronal injury. However, in addition to OGD/R, LTD4 and NMLTC4 induced cell injury and neuronal loss in mixed cultures of cortical cells, and neuronal loss and necrosis in neuron-microglial cocultures. Moreover, they induced phagocytosis and cytokine release (interleukin-1b and tumor necrosis factor-a) from primary microglia, and conditioned medium from the treated microglia induced neuronal necrosis. HAMI 3379 inhibited all of these responses, and its effects were the same as those of CysLT2R interference by CysLT2R short hairpin RNA, indicating CysLT2R dependence. In comparison, montelukast moderately inhibited OGD/R-induced primary neuronal injury and most OGD/R-and LTD4-induced (but not NMLTC4-induced) responses in mixed cultures, cocultures, and microglia. The effects of montelukast were both dependent and independent of CysLT1Rs because interference by CysLT1R small interfering RNA had limited effects on neuronal injury in neuron-microglial cocultures and on cytokine release from microglia. Our findings indicated that HAMI 3379 effectively blocked CysLT2R-mediated microglial activation, thereby indirectly attenuating ischemic neuronal injury. Therefore, CysLT2R antagonists may represent a new type of therapeutic agent in the treatment of ischemic stroke.

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“…Phospho-CREB (p-CREB) is at the hub of multiple cell-signaling cascades and regulates the expression of several downstream target genes essential for NSPCs proliferation, survival and differentiation such as brain-derived neurotrophic factor (BDNF) (Dworkin et al, 2009;Grimm et al, 2009;Mantamadiotis et al, 2012). It has been well documented that cerebral ischemia could trigger robust phosphorylation of CREB which is considered to be implicated in stroke-induced neurogenesis (Kitagawa, 2007;Tanaka et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Severe instead of mild hyperglycemia inhibits neurogenesis in the subventricular zone of adult rats after transient focal cerebral ischemia

Tan¹,

Zhi²,

Luo³

et al. 2015

Neuroscience

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Cilostazol attenuates ischemic brain injury and enhances neurogenesis in the subventricular zone of adult mice after transient focal cerebral ischemia

Cited by 57 publications

References 38 publications

Antidepressant Effects of Aripiprazole Augmentation for Cilostazol-Treated Mice Exposed to Chronic Mild Stress after Ischemic Stroke

Antidepressant Effects of Aripiprazole Augmentation for Cilostazol-Treated Mice Exposed to Chronic Mild Stress after Ischemic Stroke

HAMI 3379, a CysLT₂ Receptor Antagonist, Attenuates Ischemia-Like Neuronal Injury by Inhibiting Microglial Activation

Severe instead of mild hyperglycemia inhibits neurogenesis in the subventricular zone of adult rats after transient focal cerebral ischemia

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Cilostazol attenuates ischemic brain injury and enhances neurogenesis in the subventricular zone of adult mice after transient focal cerebral ischemia

Cited by 57 publications

References 38 publications

Antidepressant Effects of Aripiprazole Augmentation for Cilostazol-Treated Mice Exposed to Chronic Mild Stress after Ischemic Stroke

Antidepressant Effects of Aripiprazole Augmentation for Cilostazol-Treated Mice Exposed to Chronic Mild Stress after Ischemic Stroke

HAMI 3379, a CysLT2 Receptor Antagonist, Attenuates Ischemia-Like Neuronal Injury by Inhibiting Microglial Activation

Severe instead of mild hyperglycemia inhibits neurogenesis in the subventricular zone of adult rats after transient focal cerebral ischemia

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Product

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HAMI 3379, a CysLT₂ Receptor Antagonist, Attenuates Ischemia-Like Neuronal Injury by Inhibiting Microglial Activation