Interrelations between blood-brain barrier permeability and matrix metalloproteinases are differently affected by tissue plasminogen activator and hyperoxia in a rat model of embolic stroke

Michalski, Dominik; Hobohm, Carsten; Weise, Christopher M.; Heindl, Mario; Kamprad, Manja; Kacza, Johannes; Härtig, Wolfgang

doi:10.1186/2045-9912-2-2

Cited by 16 publications

(11 citation statements)

References 24 publications

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“…Strong support for this and our findings are recent data that have shown on one hand that rtPA and NBO, respectively, increases and decreases serum concentrations of matrix metalloproteinase-9, whose expression is known to be critically associated with ischemia-induced disruption of the blood-brain barrier, and on the other hand that combining oxygen and rtPA suppresses the beneficial effects of NBO at decreasing matrix metalloproteinase-9 (30). Based on these findings, the authors suggest as found in the present report that combining NBO and rtPA could not be a safe strategy (30).…”

Section: Lack Of Neuroprotective Action Of Combined Nbo and Rtpasupporting

confidence: 57%

Prothrombolytic action of normobaric oxygen given alone or in combination with recombinant tissue-plasminogen activator in a rat model of thromboembolic stroke

David

Haelewyn

Degoulet

et al. 2012

Journal of Applied Physiology

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The potential benefit of 100 vol% normobaric oxygen (NBO) for the treatment of acute ischemic stroke patients is still a matter of debate. To advance this critical question, we studied the effects of intraischemic normobaric oxygen alone or in combination with recombinant tissue-plasminogen activator (rtPA) on cerebral blood flow and ischemic brain damage and swelling in a clinically relevant rat model of thromboembolic stroke. We show that NBO provides neuroprotection by achieving cerebral blood flow restoration equivalent to 0.9 mg/kg rtPA through probable direct interaction and facilitation of the fibrinolytic properties of endogenous tPA. In contrast, combined NBO and rtPA has no neuroprotective effect on ischemic brain damage despite producing cerebral blood flow restoration. These results 1) by providing a new mechanism of action of NBO highlight together with previous findings the way by which intraischemic NBO shows beneficial action; 2) suggest that NBO could be an efficient primary care therapeutic intervention for patients eligible for rtPA therapy; 3) indicate that NBO could be an interesting alternative for patients not eligible for rtPA therapy; and 4) caution the use of NBO in combination with rtPA in acute stroke patients.

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Section: Lack Of Neuroprotective Action Of Combined Nbo and Rtpasupporting

confidence: 57%

Prothrombolytic action of normobaric oxygen given alone or in combination with recombinant tissue-plasminogen activator in a rat model of thromboembolic stroke

David

Haelewyn

Degoulet

et al. 2012

Journal of Applied Physiology

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“…44,294–295 An advantage of CORMs is that they deliver CO to tissues with reduced CO-Hb accumulation as compared with inhalation CO. 41,294 CORMs can deliver small amounts of CO in a controlled manner and may represent an experimental therapy for sepsis and inflammatory disorders. 44,294 …”

Section: Therapeutic Stategies Involving Application Of Ho-1 End Prodmentioning

confidence: 99%

“…44, 294–297 CORM-1 and CORM-2 have a hydrophobic backbone, whereas CORM-3 is water-soluble and rapidly releases CO in physiological fluids. A water-soluble boron-containing CORM (CORM-A1) has been developed, which slowly releases CO in a pH and temperature-dependent fashion.…”

Section: Therapeutic Stategies Involving Application Of Ho-1 End Prodmentioning

confidence: 99%

Targeting heme oxygenase-1 and carbon monoxide for therapeutic modulation of inflammation

Ryter

Choi

2016

Translational Research

297

224

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The heme oxygenase-1 (HO-1) enzyme system remains an attractive therapeutic target for the treatment of inflammatory conditions. HO-1, a cellular stress protein, serves a vital metabolic function as the rate-limiting step in the degradation of heme to generate carbon monoxide (CO), iron, and biliverdin-IXα (BV) which is converted to bilirubin-IXα (BR). HO-1 may function as a pleiotropic regulator of inflammatory signaling programs, through the generation of its biologically active end-products, namely CO and BV/BR. CO, when applied exogenously, can affect apoptotic, proliferative, and inflammatory cellular programs. Specifically, CO can modulate the production of pro- or anti-inflammatory cytokines and mediators. HO-1/CO may also have immunomodulatory effects with respect to regulating the functions of antigen-presenting cells, dendritic cells, and regulatory T-cells. Therapeutic strategies to modulate HO-1 in disease include the application of natural inducing compounds, as well as gene therapy approaches for the targeted genetic overexpression or knockdown of HO-1. Several compounds have been used therapeutically to inhibit HO activity, including competitive inhibitors of the metalloporphyrin series, or non-competitive isoform-selective derivatives of imidazole-dioxolanes. The end-products of HO activity, BV/BR and CO may be used therapeutically as pharmacological treatments. CO may be applied by inhalation, or through the use of CO releasing molecules (CORMs). This review will discuss HO-1 as a therapeutic target in diseases involving inflammation, including lung and vascular injury, sepsis, ischemia/reperfusion injury and transplant rejection.

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“…Acute lung injury (ALI) and its most severe manifestation, acute respiratory distress syndrome (ARDS), is a clinical syndrome characterized by acute hypoxemic respiratory failure, bilateral pulmonary infiltrates on frontal chest radiograph consistent with edema, and normal cardiac filling pressures [ 1 ]. The resulting lung damage can evoke lung failure and multiple organ dysfunctions associated with increased mortality [ 2 ]. Sepsis (the presence of pus-forming bacteria or their toxins in the blood or tissues) is one of the most important ALI/ARDS causes [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

In vivo study of the effects of exogenous hydrogen sulfide on lung mitochondria in acute lung injury in rats

Wang

Zhang

et al. 2014

BMC Anesthesiol

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BackgroundAcute lung injury (ALI) is a serious disease with high incidence in ICU, and impaired mitochondria function plays a significant role in ALI. In this study, we examined the possible roles of exogenous hydrogen sulfide (H2S) in lung mitochondria regulation in ALI rats.MethodsThe rat ALI model was induced by an intra-tongue vein Lipopolysaccharide (LPS) injection. We used sodium hydrosulphide (NaHS) as the H2S donor. We randomly divided 40 Sprague–Dawley rats into five groups: control, LPS injury, LPS + low-dose NaHS (0.78 mg•kg-1), LPS + middle-dose NaHS (1.56 mg•kg-1), and LPS + high-dose NaHS (3.12 mg•kg-1). Rats were killed 3 h after NaHS administration. We calculated a semi-quantitative histological index of lung injury assessments and measured the lung wet-to-dry weight ratio. We further analyzed serum for interleukin-1β levels using enzyme-linked immunosorbent assays. We observed lung mitochondria ultrastructures with an electron microscope. We examined oxidative stress markers in lung mitochondria and the mitochondrial swelling and activity. We analyzed lung mitochondria and cytosol Cyt-c protein expression using Western blotting.ResultsCompared to the control group, the quantitative assessment score index, wet-to-dry weight ratios, and interleukin-1β content in the LPS injury group were significantly increased and the mitochondrial ultrastructure damaged. Furthermore, mitochondrial activity, adenosine triphosphatease, superoxide dismutase, glutathione peroxidase, and mitochondrial Cyt-c protein expression were significantly decreased, and malondialdehyde content, mitochondrial swelling, and cytosol Cyt-c protein expression were significantly increased in the LPS injury group compared to the control group. These effects were lessened by NaHS.ConclusionExogenous H2S provided a protective effect against ALI by decreasing the mitochondrial lipid peroxidation level and protecting the cell structure in the LPS-induced rat models. Its regulatory effect on lung mitochondria is positively correlated with the dosage.

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Interrelations between blood-brain barrier permeability and matrix metalloproteinases are differently affected by tissue plasminogen activator and hyperoxia in a rat model of embolic stroke

Cited by 16 publications

References 24 publications

Prothrombolytic action of normobaric oxygen given alone or in combination with recombinant tissue-plasminogen activator in a rat model of thromboembolic stroke

Prothrombolytic action of normobaric oxygen given alone or in combination with recombinant tissue-plasminogen activator in a rat model of thromboembolic stroke

Targeting heme oxygenase-1 and carbon monoxide for therapeutic modulation of inflammation

In vivo study of the effects of exogenous hydrogen sulfide on lung mitochondria in acute lung injury in rats

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