病人发生中风后大脑受损部位会有炎性反应。直到现在，炎性反应一直被视为疾病产生的消极后果，需要尽快清除。但是事实证明，炎症也有一些积极的方面，比如它可以帮助大脑自我修复。
“这与我们之前的观念形成反差”，瑞典隆德大学Zaal Kokaia教授说。
当发生中风时，大脑的受损区域神经细胞会死亡，从而吸引免疫系统的细胞参与炎性反应。其中你会发现一种单核细胞(在骨髓中产生的白细胞)。
单核细胞会进入发炎区域，在这里它们会发展成巨噬细胞以便清除坏死组织。但这并不是它们做的一切，它们还会分泌物质来帮助大脑进行修复。
随着时间的推移大多数中风患者会恢复至少一部分病情。这种自我改善是众所周知的，但不是确切原因。隆德的研究人员认为，改善部分是由于通过免疫细胞进行的物质释放。
在他们的研究中执行着相反的实验：在中风的动物模型中他们能够从血液中去除单核细胞。相比免疫系统正常工作的小鼠，携带有减少循环单核细胞数量的小鼠不能再患中风后很好的恢复。
目前治疗中风主要通过溶解或消除血栓。然而，这样的治疗必须在受损后的早期阶段进行，这意味着大多数中风患者因为太迟而不能进行及时治疗。未来的治疗方法——基于隆德研究者的新发现可以促进自愈。这种治疗方法可在某种程度上前几周内进行治疗，而不是在中风发生后的最初数小时内治疗。
研究者关注后期阶段大脑的变化。研究表明中风后大脑会从干细胞中产生新的神经细胞。他们现在要进行动物实验来观察是否可以通过添加更多的单核细胞到大脑中用来改善自我修复功能，或通过刺激骨髓中的单核细胞促进生产。
“很明显，小鼠和人类是有区别的，但没有迹象表明，两者的大脑功能在这方面不同” Olle Lindvall说。
他认为，炎症的积极影响这个新观点也可以应用于其他疾病。研究小组的合作者发现以色列脊髓损伤的病例中获得类似的结果。
“这是在研究中不少于一个的典范转移，在许多情况下炎症被视为一个纯粹的疾病反应消极现象，应该通过任何手段来处理炎症反应。我们现在意识到这种观点太简单了。”Olle Lindvall说。
Monocyte-Derived Macrophages Contributeto Spontaneous Long-Term Functional Recovery after Stroke in Mice
Somsak Wattananit1, Daniel Tornero1,Nadine Graubardt3, Tamar Memanishvili1,4, Emanuela Monni1, Jemal Tatarishvili1,Giedre Miskinyte1, Ruimin Ge1, Henrik Ahlenius2, Olle Lindvall1, MichalSchwartz3, and Zaal Kokaia1
doi: 10.1523/JNEUROSCI.4317-15.2016
Stroke is a leading cause of disabilityand currently lacks effective therapy enabling long-term functional recovery.Ischemic brain injury causes local inflammation, which involves both activatedresident microglia and infiltrating immune cells, including monocytes.Monocyte-derived macrophages (MDMs) exhibit a high degree of functionalplasticity. Here, we determined the role of MDMs in long-term spontaneousfunctional recovery after middle cerebral artery occlusion in mice. Analyses byflow cytometry and immunocytochemistry revealed that monocytes home to thestroke-injured hemisphere., and that infiltration peaks 3 d after stroke. Atday 7, half of the infiltrating MDMs exhibited a bias toward a proinflammatoryphenotype and the other half toward an anti-inflammatory phenotype, but duringthe subsequent 2 weeks, MDMs with an anti-inflammatory phenotype dominated.Blocking monocyte recruitment using the anti-CCR2 antibody MC-21 during thefirst week after stroke abolished long-term behavioral recovery, as determinedin corridor and staircase tests, and drastically decreased tissue expression ofanti-inflammatory genes, including TGFβ, CD163, and Ym1. Our results show thatspontaneously recruited monocytes to the injured brain early after the insultcontribute to long-term functional recovery after stroke. SIGNIFICANCESTATEMENT For decades, any involvement of circulating immune cells in CNSrepair was completely denied. Only over the past few years has involvement ofmonocyte-derived macrophages (MDMs) in CNS repair received appreciation. Weshow here, for the first time, that MDMs recruited to the injured brain earlyafter ischemic stroke contribute to long-term spontaneous functional recoverythrough inflammation-resolving activity. Our data raise the possibility thatinadequate recruitment of MDMs to the brain after stroke underlies theincomplete functional recovery seen in patients and that boosting homing ofMDMs with an anti-inflammatory bias to the injured brain tissue may be a newtherapeutic approach to promote long-term improvement after stroke.
来源：生物谷
转自：cell
