Systemic inflammatory challenges compromise survival after experimental stroke via augmenting brain inflammation, blood- brain barrier damage and brain oedema independently of infarct size.
Systemic inflammatory challenges compromise survival after experimental stroke via augmenting brain inflammation, blood- brain barrier damage and brain oedema independently of infarct size.
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DOI：
10.1186/1742-2094-8-164
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发表时间：
2011-11-24
影响因子：
9.3
通讯作者：
Kovács KJ
中科院分区：
文献类型：
--
作者：
Dénes A;Ferenczi S;Kovács KJ
全身性炎症损害脑卒中患者和实验动物的预后，其机制尚不清楚。循环炎症介质可以激活脑内的脑血管内皮或神经胶质细胞，并对缺血性脑损伤有影响。脑缺血最严重的早期临床并发症之一是脑水肿，它会在最初的24-48小时内影响患者的生存。目前尚不清楚全身性炎症是否仅通过增加脑损伤来损害卒中后的预后，或者它们是否对脑水肿、脑血管炎症和血脑屏障损伤有直接影响。采用两种不同的全身炎症刺激，急性内毒素治疗和过敏反应来研究大脑中动脉闭塞（MCAo）后脑损伤的机制。采用组织学方法对缺血性脑损伤、血脑屏障损伤及水肿进行分析。采用细胞头阵列、免疫荧光、原位杂交和实时荧光定量PCR分析大鼠全身细胞因子反应和脑内炎症变化。与梗死面积的增加无关，全身性炎症在小鼠脑卒中后的头24小时内严重损害了小鼠的生存。系统性脂多糖（LPS）剂量依赖性地增加脑缺血后数分钟至数小时的死亡率（50-100%）。卵清蛋白致敏小鼠急性过敏性刺激对脑卒中的影响，腹腔注射比静脉注射更严重。脂多糖和过敏反应在实验性中风前都引起了血液和大脑的炎症变化。LPS治疗后血浆细胞因子水平明显升高，过敏反应后IL-10水平升高。MCAo后，LPS和过敏反应均增加了小胶质细胞白细胞介素-1α (IL-1α)的表达和血脑屏障的破坏。LPS引起整个同侧半球明显的粒细胞募集。为了研究减少缺血性损伤是否可以改善全身性炎症的预后，我们进行了控制低温治疗。在所有治疗组中，低温降低了梗死面积，中等程度地提高了生存率，但未能减少过敏反应和lps诱导的神经炎症后过度水肿的形成。我们的研究结果表明，全身性炎症通过多种机制诱导脑血管炎症。脑炎症增加、血脑屏障损伤和脑水肿形成可能是实验性脑卒中后小鼠全身炎症刺激受损的主要原因，与梗死面积无关。
Systemic inflammation impairs outcome in stroke patients and experimental animals via mechanisms which are poorly understood. Circulating inflammatory mediators can activate cerebrovascular endothelium or glial cells in the brain and impact on ischaemic brain injury. One of the most serious early clinical complications of cerebral ischaemia is brain oedema, which compromises survival in the first 24-48 h. It is not understood whether systemic inflammatory challenges impair outcome after stroke by increasing brain injury only or whether they have direct effects on brain oedema, cerebrovascular inflammation and blood-brain barrier damage. We used two different systemic inflammatory stimuli, acute endotoxin treatment and anaphylaxis to study mechanisms of brain injury after middle cerebral artery occlusion (MCAo). Ischaemic brain injury, blood-brain barrier damage and oedema were analysed by histological techniques. Systemic cytokine responses and inflammatory changes in the brain were analysed by cytometric bead array, immunofluorescence, in situ hibridization and quantitative real-time PCR. Systemic inflammatory challenges profoundly impaired survival in the first 24 h after experimental stroke in mice, independently of an increase in infarct size. Systemic lipopolysaccharide (LPS) dose-dependently increased mortality (50-100%) minutes to hours after cerebral ischaemia. Acute anaphylactic challenge in ovalbumin-sensitised mice affected stroke more seriously when induced via intraperitoneal administration compared to intravenous. Both LPS and anaphylaxis induced inflammatory changes in the blood and in the brain prior to experimental stroke. Plasma cytokine levels were significantly higher after LPS, while increased IL-10 levels were seen after anaphylaxis. After MCAo, both LPS and anaphylaxis increased microglial interleukin-1α (IL-1α) expression and blood-brain barrier breakdown. LPS caused marked granulocyte recruitment throughout the ipsilateral hemisphere. To investigate whether reduction of ischaemic damage can improve outcome in systemic inflammation, controlled hypothermia was performed. Hypothermia reduced infarct size in all treatment groups and moderately improved survival, but failed to reduce excess oedema formation after anaphylaxis and LPS-induced neuroinflammation. Our results suggest that systemic inflammatory conditions induce cerebrovascular inflammation via diverse mechanisms. Increased brain inflammation, blood-brain barrier injury and brain oedema formation can be major contributors to impaired outcome in mice after experimental stroke with systemic inflammatory stimuli, independently of infarct size.
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DOI：
10.1164/rccm.200801-008oc
发表时间：
2008-10-15
影响因子：
24.7
作者：
Lee, Kyung Sun;Kim, So Ri;Lee, Yong Chul
通讯作者：
Lee, Yong Chul
影响因子：
5.3
作者：
McColl, Barry W.;Rothwell, Nancy J.;Allan, Stuart M.
通讯作者：
Allan, Stuart M.
影响因子：
37.8
作者：
Caso, Javier R.;Pradillo, Jesus M.;Lizasoain, Ignacio
通讯作者：
Lizasoain, Ignacio
影响因子：
82.9
作者：
Liesz, Arthur;Suri-Payer, Elisabeth;Veltkamp, Roland
通讯作者：
Veltkamp, Roland
影响因子：
5.3
作者：
McColl, Barry W.;Rothwell, Nancy J.;Allan, Stuart M.
通讯作者：
Allan, Stuart M.