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Cu-diacetyl-bis (N4-methylthiosemicarbazone) (CuATSM) has both anti-oxidative and anti-inflammatory activities, but its therapeutic efficacy for oxidative stress has not been thoroughly investigated in acute ischemic stroke. Here, the present study was designed to assess the efficacies of CuATSM in acute ischemic stroke by comparing with the standard neuroprotective reagent edaravone. Mice were subjected to transient middle cerebral occlusion (tMCAO) for 60 min, and then intravenously administrated with CuATSM (1.5 mg/kg) or edaravone (3 mg/kg) just after the reperfusion, and examined at 1 and 3 d. Compared with the vehicle group, CuATSM treatment decreased infarct volumes and oxidative stress at 3d after tMCAO, which was further enhanced by combined CuATSM + edaravone treatment as compared with single CuATSM group, but not improve neurobehaviors. The present study demonstrated that CuATSM showed strong antioxidative and neuroprotective effects in acute ischemic stroke, which was enhanced by the combination with edaravone., Competing Interests: Declaration of Competing Interest The authors disclose no potential conflict of interests., (Copyright © 2020 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.)

Background: During an acute stroke, reactive oxygen species are overproduced and the endogenous antioxidative defense systems are disrupted. Therefore, antioxidative therapy can be a promising scheme to reduce the severity of stroke. Neumentix is a novel antioxidative supplement produced from a patented mint line and contains a high content of rosmarinic acid (RA). Although Neumentix has proven diverse efficacy and safety in clinical trials, its effect on strokes is unclear., Methods: Mice that were treated with Neumentix or vehicle for 14 days underwent transient middle cerebral artery occlusion (tMCAO) for 60 min. Mice were sacrificed 5 days after tMCAO., Results: Neumentix preserved body weight after tMCAO, showed a high antioxidative effect in serum, and reduced infarction volume compared to the vehicle. The expression of 4-hydroxy-2-nonenal, Nε-(carboxymethyl) lysine, and 8-hydroxy-2'-deoxyguanosine was reduced in Neumentix-treated mice., Conclusion: The antioxidative effect of Neumentix was confirmed. This is the first report to demonstrate the antioxidative effect of Neumentix on strokes., Competing Interests: Declaration of Competing Interest The authors disclose no potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Cerebral ischemia causes a strong inflammatory response. Neumentix is a dietary supplement containing 14.9% rosmarinic acid and 29.9% total phenolic content, which has been proved to be beneficial against inflammatory response. Therefore, Neumentix's effect on anti-inflammatory and blood brain barrier (BBB) disruption in transient middle cerebral artery occlusion (tMCAO) model mice is investigated in this study., Methods: After the pretreatment of vehicle or Neumentix 134 mg/kg/d, intraperitoneal injection (i.p.) (containing rosmarinic acid 20 mg/kg/d) for 14 days, mice were subjected to tMCAO for 60 min and kept receiving vehicle or Neumentix daily 5 days afterward., Results: Neumentix treatment ameliorated neurobehavioral impairment in the corner test (5d after tMCAO, **P<0.01), reduced infarct volume (#P<0.05), suppressed expression of ionized calciumbinding adapter molecule-1 (Iba-1), tumor necrosis factor alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) (###P<0.001), and improved the integrity of BBB (§P<0.05) at 5 days after tMCAO., Conclusion: The present study provided an evidence of Neumentix's anti-inflammatory and neuroprotection effect against BBB disruption on experimental tMCAO model mice, suggesting that Neumentix could be a potential therapeutic agent for stroke., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Telmisartan is a highly lipid-soluble angiotensin receptor blocker (ARB), which improves insulin sensitivity and reduces triglyceride levels and, thus, is called metabo-sartan. We examined the effects of telmisartan on neurovascular unit (N-acetylglucosamine oligomer [NAGO], collagen IV, and glial fibrillary acidic protein [GFAP]) and neuroinflammation (matrix metalloproteinase-9 [MMP-9] and inflammasome) in brain of stroke-resistant spontaneously hypertensive rat (SHR-SR). At 12 weeks of age, SHR-SR received transient middle cerebral artery occlusion (tMCAO) for 90 minutes and were divided into the following 3 groups, that is, vehicle group, low-dose telmisartan group (.3 mg/kg/d), and high-dose telmisartan group (3 mg/kg/d, postoral). Immunohistologic analysis at ages 6, 12, and 18 months showed progressive decreases of NAGO-positive endothelium and collagen IV-positive basement membrane and progressive increases of MMP-9-positive neurons, GFAP-positive astrocytes, and NLRP3-positive inflammasome in the cerebral cortex of vehicle group. Low-dose telmisartan reduced such changes without lowering blood pressure (BP), and high-dose telmisartan further improved such changes with lowering BP. The present findings suggest that a persistent hypertension caused a long-lasting inflammation after tMCAO in SHR-SR, which accelerated neurovascular disruption and emergent inflammasome, and that telmisartan greatly reduced such inflammation and protected the neurovascular unit via its pleiotropic effects in living hypertensive rat brain after ischemic stroke., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Ischemic stroke is a major neurologic disorder and a leading cause of disability and death in the world. We compared neuroprotective effects of single or combination therapy of amlodipine (AM) and atorvastatin (AT) in such a metabolic syndrome model Zucker rat. The animals were pretreated with vehicle, AM, AT, or the combination of AM plus AT for 28days, and physical and serum parameters were analyzed, then 90min of transient middle cerebral artery occlusion (tMCAO), was performed followed by immunohistochemical analyses at 24h. Without affecting serum levels of lipids, adiponectin, and leptin, the combination therapy of AM plus AT ameliorated the post-ischemic brain weight increase. The single treatment with AM or AT itself exerted neuroprotective effects with reducing inductions of MMP-9 and AT2R, as well as with preserving collagen IV, and the combination therapy of AM plus AT showed a further synergistic benefit against acute ischemic neural damages. Single AT was more protective on these 3 molecules than single AM at this time point of 24h after tMCAO. Thus, the combination therapy with AM plus AT extended the neuroprotectives effect of single treatment with AM or AT on a part of neurovascular unit and a hypertension-related receptor., (Copyright © 2011 Elsevier B.V. All rights reserved.)