Post-stroke infections exacerbate ischemic brain injury in middle-aged rats: immunomodulation and neuroprotection by progesterone.
Post-stroke infections exacerbate ischemic brain injury in middle-aged rats: immunomodulation and neuroprotection by progesterone.
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DOI：
10.1016/j.neuroscience.2012.10.017
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发表时间：
2013-06-03
期刊：
影响因子：
3.3
通讯作者：
Stein, D. G.
中科院分区：
文献类型：
--
作者：
Yousuf, S.;Atif, F.;Sayeed, I.;Wang, J.;Stein, D. G.
我们研究了延迟、延长的全身性炎症对中年大鼠卒中结局和孕酮（P4）神经保护作用的影响。在短暂的大脑中动脉闭塞/再灌注（MCAO）手术后，大鼠在闭塞后2 h、6 h和每24 h接受P4（8或16 mg/kg）或载体注射，直到第7天。在损伤后24小时，通过给予3个剂量的脂多糖（LPS; 50 mg/kg，间隔4小时）来诱导全身炎症以模拟中风后感染。我们测量了血清脑源性神经营养因子（BDNF），促炎细胞因子，并在多个时间的行为参数。在伤后第3天和第7天，载体+LPS组的血清BDNF水平比单独载体组下降更多（P<0.05）。单独溶媒组在卒中后不同时间显示IL-1β、IL-6和TNFα水平显著升高，溶媒+LPS组这些水平进一步升高。与媒介物和媒介物+LPS相比，两种剂量的P4产生细胞因子水平的显著（P<0.05）下降。P4组脑源性神经营养因子水平在脑卒中后3、7 d恢复正常（P<0.05）。在中风后3、5和7天的行为评估（旋转棒、握力、感觉忽略和自发活动测试）揭示，与完整对照相比，载体组在所有测试中具有显著（P<0.05）缺陷，并且载体+LPS组的表现更差。两种剂量的P4在所有测试中均产生显著的功能改善。全身炎症对梗死体积没有表现出累加效应，但两种剂量的P4均显示出明显的梗死减少。我们认为，中风后感染加重中风的结果和P4发挥神经保护/调节作用，通过其全身抗炎和BDNF的调节作用。
We investigated the effect of delayed, prolonged systemic inflammation on stroke outcomes and progesterone (P4) neuroprotection in middle-aged rats. After transient middle cerebral artery occlusion/reperfusion (MCAO) surgery, rats received P4 (8 or 16 mg/kg) or vehicle injections at 2h, 6h and every 24h until day 7 post-occlusion. At 24h post-injury systemic inflammation was induced by giving 3 doses of lipopolysaccharide (LPS; 50 mg/kg, at 4h intervals) to model post-stroke infections. We measured serum brain-derived neurotrophic factor (BDNF), pro-inflammatory cytokines, and behavioral parameters at multiple times. Serum BDNF levels decreased more in the vehicle+LPS group compared to vehicle-alone at 3 and 7 days post-injury (P<0.05). Vehicle-alone showed a significant increase in IL-1β, IL-6, and TNFα levels at different times following stroke and these levels were further elevated in the vehicle+LPS group. P4 at both doses produced a significant (P<0.05) decline in cytokine levels compared to vehicle and vehicle+LPS. P4 restored BDNF levels at 3 and 7 days post-stroke (P<0.05). Behavioral assessment (rotarod, grip strength, sensory neglect and locomotor activity tests) at 3, 5 and 7 days post-stroke revealed that the vehicle group had significant (P<0.05) deficits in all tests compared to intact controls, and performance was worse in the vehicle+LPS group. P4 at both doses produced significant functional improvement on all tests. Systemic inflammation did not show an additive effect on infarct volume but P4 at both doses showed significant infarct reduction. We suggest that post-stroke infection exacerbates stroke outcomes and P4 exerts neuroprotective/modulatory effects through its systemic anti-inflammatory and BDNF regulatory actions.
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影响因子：
3.3
作者：
Ishrat T;Sayeed I;Atif F;Hua F;Stein DG
通讯作者：
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DOI：
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发表时间：
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影响因子：
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