Minocycline-Suppression of Early Peripheral Inflammation Reduces Hypoxia-Induced Neonatal Brain Injury.
Minocycline-Suppression of Early Peripheral Inflammation Reduces Hypoxia-Induced Neonatal Brain Injury.
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米诺环素抑制早期周围炎症可减少缺氧引起的新生儿脑损伤
DOI：
10.3389/fnins.2017.00511
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发表时间：
2017
影响因子：
4.3
通讯作者：
Li F
中科院分区：
文献类型：
--
作者：
Min Y;Li H;Xu K;Huang Y;Xiao J;Wang W;Li L;Yang T;Huang L;Yang L;Jiang H;Wang Q;Zhao M;Hua H;Mei R;Li F
虽然大量研究报道新生儿缺氧缺血（HI）通过脑中的炎症反应诱导长期认知障碍，但对早期外周炎症反应在HI损伤中的作用知之甚少。在此，我们使用新生缺氧啮齿动物模型，通过使出生后0天（P0 d）的大鼠幼仔经受全身缺氧（3.5h），这是临床新生儿中常见的条件。低氧暴露结束后2 h，随后每日给予一半剂量（22.5 mg/kg）米诺环素治疗，连续6 d。注射生理盐水作为溶剂对照。研究早期外周炎症如何对缺氧做出反应，以及这种外周炎症反应是否与认知缺陷相关。我们发现新生儿缺氧不仅显著增加血液中的白细胞，而且还增加中枢神经系统（CNS）中的单核细胞，表现为C-C趋化因子受体2型（CCR 2+）/CD 11b + CD 45+阳性细胞的存在和CCR 2蛋白表达水平。外周炎症反应的早期发作之后是通过细胞因子IL-1β和离子钙结合衔接分子1（Iba-1;活化的小胶质细胞标志物）的水平证明的脑炎症的晚期发作。缺氧后血脑屏障（BBB）破坏，髓鞘形成减少，学习记忆功能减退。有趣的是，认知功能与缺氧诱导的白细胞反应高度相关。值得注意的是，即使在缺氧开始后给予米诺环素也能显著抑制白细胞介导的炎症以及脑炎症，这表明在全身性缺氧诱导的脑损伤中具有神经保护作用。我们的数据提供了新的见解，即系统性缺氧诱导认知功能障碍，这涉及白细胞介导的外周炎症反应。
While extensive studies report that neonatal hypoxia-ischemia (HI) induces long-term cognitive impairment via inflammatory responses in the brain, little is known about the role of early peripheral inflammation response in HI injury. Here we used a neonatal hypoxia rodent model by subjecting postnatal day 0 (P0d) rat pups to systemic hypoxia (3.5 h), a condition that is commonly seen in clinic neonates, Then, an initial dose of minocycline (45 mg/kg) was injected intraperitoneally (i.p.) 2 h after the hypoxia exposure ended, followed by half dosage (22.5 mg/kg) minocycline treatment for next 6 consecutive days daily. Saline was injected as vehicle control. To examine how early peripheral inflammation responded to hypoxia and whether this peripheral inflammation response was associated to cognitive deficits. We found that neonatal hypoxia significantly increased leukocytes not only in blood, but also increased the monocytes in central nervous system (CNS), indicated by presence of C-C chemokine receptor type 2 (CCR2+)/CD11b+CD45+ positive cells and CCR2 protein expression level. The early onset of peripheral inflammation response was followed by a late onset of brain inflammation that was demonstrated by level of cytokine IL-1β and ionized calcium binding adapter molecule 1(Iba-1; activated microglial cell marker). Interrupted blood-brain barrier (BBB), hypomyelination and learning and memory deficits were seen after hypoxia. Interestingly, the cognitive function was highly correlated with hypoxia-induced leukocyte response. Notably, administration of minocycline even after the onset of hypoxia significantly suppressed leukocyte-mediated inflammation as well as brain inflammation, demonstrating neuroprotection in systemic hypoxia-induced brain damage. Our data provided new insights that systemic hypoxia induces cognitive dysfunction, which involves the leukocyte-mediated peripheral inflammation response.
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影响因子：
6.9
作者：
Khan, Mohammad Badruzzaman;Hoda, Md Nasrul;Vaibhav, Kumar;Giri, Shailendra;Wang, Philip;Waller, Jennifer L.;Ergul, Adviye;Dhandapani, Krishnan M.;Fagan, Susan C.;Hess, David C.
通讯作者：
Hess, David C.
影响因子：
6.2
作者：
Arnoux, Isabelle;Hoshiko, Maki;Audinat, Etienne
通讯作者：
Audinat, Etienne
DOI：
10.1007/978-3-7091-0693-8_35
发表时间：
2011-01-01
期刊：
INTRACEREBRAL HEMORRHAGE RESEARCH: FROM BENCH TO BEDSIDE
影响因子：
--
作者：
Khatibi, Nikan H.;Lee, Lillian K.;Zhang, John H.
通讯作者：
Zhang, John H.
影响因子：
3.6
作者：
Meng, SZ;Qiao, M;Tuor, UI
通讯作者：
Tuor, UI
影响因子：
3.3
作者：
Prinz, Marco;Priller, Josef
通讯作者：
Priller, Josef