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[Display omitted] • sPlas significantly reduced cerebral ischemic infarction in mice at 5 d after tMCAO. • sPlas significantly alleviated neural oxidative stress in mice at 5 d after tMCAO. • sPlas significantly regulated neural inflammation in mice at 5 d after tMCAO. • sPlas significantly attenuated neurovascular unit damage in mice at 5 d after tMCAO. • sPlas may be a preventive and therapeutic candidate against ischemic stroke. Scallop-derived plasmalogen (sPlas) has both anti-oxidative and anti-inflammation activities, but its efficacy has not been investigated in ischemic stroke models where oxidative stress, inflammation, and neurovascular unit (NVU) damage accelerates pathophysiological progression. Therefore, in the present study, we aimed to assess the neuroprotective effects of sPlas in ischemic stroke by using a transient middle cerebral artery occlusion (tMCAO) mouse model. After the pretreatment of vehicle or sPlas (10 mg/kg/day) for 14 days, adult male mice were subjected to tMCAO for 60 min, then continuously treated with vehicle or sPlas during reperfusion and for an additional 5 days. The administration of sPlas significantly improved motor deficits (corner and rotarod tests, * p < 0.05 vs vehicle), enhanced serum antioxidative activity (OXY-adsorbent and d-ROMs tests, * p < 0.05 vs vehicle), reduced infarction volume (* p < 0.05 vs vehicle), decreased the expression of two oxidative stress markers, 4-HNE (* p < 0.05 vs vehicle) and 8-OHdG (* p < 0.05 vs vehicle), decreased the expression of pro-inflammatory markers Iba-1 (** p < 0.01 vs vehicle), IL-1β (** p < 0.01 vs vehicle), and TNF-α (** p < 0.01 vs vehicle), and alleviated NVU damage (collagen IV, MMP9, and GFAP/collagen IV, * p < 0.05 vs vehicle). Our present findings are the first to demonstrate the neuroprotective effects of sPlas on acute ischemic stroke mice at 5 d after tMCAO via anti-oxidative stress, anti-inflammation, and improvement of NVU damage, suggesting the potential of sPlas in preventing and treating ischemic stroke. [ABSTRACT FROM AUTHOR]

Carnosine (β-alanyl-L-histidine) is a natural dipeptide with multiple neuroprotective properties. Previous studies have advertised that carnosine scavenges free radicals and displays anti-inflammatory activity. However, the underlying mechanism and the efficacies of its pleiotropic effect on prevention remained obscure. In this study, we aimed to investigate the anti-oxidative, anti-inflammative, and anti-pyroptotic effects of carnosine in the transient middle cerebral artery occlusion (tMCAO) mouse model. After a daily pre-treatment of saline or carnosine (1000 mg / kg / day) for 14 days, mice (n = 24) were subjected to tMCAO for 60 min and continuously treated with saline or carnosine for additional 1 and 5 days after reperfusion. The administration of carnosine significantly decreased infarct volume 5 days after the tMCAO (* p < 0.05) and effectively suppressed the expression of 4-HNE, 8-OHdG, Nitrotyrosine 5 days, and RAGE 5 days after tMCAO. Moreover, the expression of IL-1 β was also significantly suppressed 5 days after tMCAO. Our present findings demonstrated that carnosine effectively relieves oxidative stress caused by ischemic stroke and significantly attenuates neuroinflammatory responses related to IL-1 β , suggesting that carnosine can be a promising therapeutic strategy for ischemic stroke. [Display omitted] • Carnosine significantly reduced infarct volume 5 days after tMCAO. • Carnosine significantly alleviated neural oxidative stress 1 and 5 days after tMCAO. • Carnosine significantly regulated inflammation marker expression 5 days after tMCAO. [ABSTRACT FROM AUTHOR]

Abstract: Although peroxisome proliferator-activated receptor-γ (PPARγ) and adenosine A2A receptor (A2AR) are reported to be anti-inflammatory factors in acute lung injury (ALI), their internal link and synergic or antagonistic effect after activation are poorly understood. Here, we found that PPARγ and A2AR could upregulate the mRNA and protein expressions of each other in lung tissues of LPS-induced mouse ALI model and murine macrophages. Further investigation demonstrated that PPARγ upregulated A2AR expression by directly binding to a DR10 response element (−218 to −197) within A2AR gene promoter region. Instead of directly interacting with PPARγ, A2AR stimulated PPARγ expression via protein kinase A (PKA)–cAMP response element binding protein (CREB) signaling by provoking the binding of CREB to a cAMP responsive element (CRE)-like site in PPARγ gene promoter region. In addition, combination of PPARγ and A2AR agonists was found to exert obviously better effect on suppressing neutrophil infiltration and inflammatory cytokine expressions, attenuating lung edema, pathological changes and improving lung function of blood gas exchange than their single application. These findings reveal a novel functional positive feedback loop between PPARγ and A2AR signaling to potentialize their effect on inhibiting inflammation and attenuating lung damages in ALI. It suggests that targeting this PPARγ–A2AR signaling rather than PPARγ or A2AR alone may be a more attractive and efficient potential therapeutic strategy for ALI. [Copyright &y& Elsevier]

Abstract: The antagonism or genetic deletion of adenosine A2A receptors has been shown to exacerbate tissue damage in acute lung injury. Caffeine, a widely consumed behavioral drug, acts as a non-selective antagonist of A2A receptor and also has additional pharmacological effects. Thus, the protective vs. deleterious effects of caffeine in acute lung injury should be evaluated. In a murine oleic acid-induced model of acute lung injury, we found that chronic caffeine treatment by drinking water (0.1g/l or 0.25g/l for 2weeks before acute lung injury) or acute caffeine treatment at high dose (i.p. 50mg/kg, injection, 30min before acute lung injury) significantly attenuated the lung edema, hemorrhage, neutrophil recruitment as well as the inflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) expressions in both of the wild type (WT) and A2A receptor knockout (KO) mice. This profile was accompanied by increased cAMP levels and up-regulation of A2B receptor mRNAs in the lungs. In contrast, acute caffeine treatment at low dose (i.p. 5mg/kg or 15mg/kg, injection, 30min before acute lung injury) enhanced the inflammation and lung damage in WT mice with decreasing cAMP but not in A2A receptor KO mice. These results indicate that caffeine either enhances lung damage by antagonizing A2A receptor or exerts protection against lung damage via A2A receptor-independent mechanisms, depending on the timing of exposure (chronic vs. acute) and dose of administration (low vs. high). These findings provide new insight of caffeine in acute lung injury and highlight the potential benefit and strategy of caffeine intake or administration for preventing acute lung injury. [Copyright &y& Elsevier]