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首页> 外文期刊>Medical Gas Research >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
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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

机译：在栓塞性中风大鼠模型中，组织纤溶酶原激活物和高氧血症对血脑屏障通透性与基质金属蛋白酶之间的关系有不同的影响

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Background In ischemic stroke, blood-brain barrier (BBB) regulations, typically involving matrix metalloproteinases (MMPs) and inhibitors (TIMPs) as mediators, became interesting since tissue plasminogen activator (tPA)-related BBB breakdown with risk of secondary hemorrhage was considered to involve these mediators too. Despite high clinical relevance, detailed interactions are purely understood. After a pilot study addressing hyperoxia as potential neuroprotective co-treatment to tPA, we analyzed interrelations between BBB permeability (BBB-P), MMPs and TIMPs. Findings Rats underwent embolic middle cerebral artery occlusion (eMCAO) and treatment with normobaric (NBO) or hyperbaric oxygen (HBO), tPA, tPA+HBO, or no treatment. BBB-P was assessed by intravenously applied FITC-albumin at 4 or 24 hours. MMP-2/-9 and TIMP-1/-2 serum levels were determined at 5 or 25 hours. Time point-corrected partial correlations were used to explore interrelations of BBB-P in ischemic regions (extra-/intravasal FITC-albumin ratio) and related serum markers. BBB-P correlated positively with MMP-2 and MMP-9 in controls, whereas hyperoxia led to an inverse association, most pronounced for HBO/MMP-9 (r = -0.606; P Conclusions HBO was found to reverse the positively directed interrelation of BBB-P and MMPs after eMCAO, but this effect failed to sustain in the expected amount when HBO and tPA were given simultaneously.
机译：背景技术在缺血性卒中中，通常涉及基质金属蛋白酶（MMP）和抑制剂（TIMP）作为介体的血脑屏障（BBB）法规引起了人们的关注，因为组织纤溶酶原激活剂（tPA）相关的BBB分解被认为具有继发性出血的风险也需要这些调解人参与。尽管具有高度的临床相关性，但完全可以理解详细的相互作用。在一项针对高氧血症作为tPA潜在的神经保护性协同治疗的初步研究之后，我们分析了BBB通透性（BBB-P），MMP和TIMP之间的相互关系。结果大鼠经历了栓塞性大脑中动脉闭塞（eMCAO），并用常压（NBO）或高压氧（HBO），tPA，tPA + HBO进行治疗，或不进行任何治疗。在4或24小时通过静脉内施用FITC-白蛋白评估BBB-P。在5或25小时测定MMP-2 / -9和TIMP-1 / -2血清水平。使用时间点校正的局部相关性探讨缺血区域中BBB-P的相互关系（血管内/血管内FITC-白蛋白比）和相关的血清标志物。 BBB-P在对照组中与MMP-2和MMP-9呈正相关，而高氧导致逆相关，对于HBO / MMP-9最为明显（r = -0.606; P结论HBO被发现逆转了正向相关性。 eMCAO后出现BBB-P和MMP，但是当同时给予HBO和tPA时，这种作用未能维持在预期的量。

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