Denes Adam, Vidyasagar Rishma, Feng Jianghua, Narvainen Johanna, McColl Barry W, Kauppinen Risto A, Allan Stuart M
Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
J Cereb Blood Flow Metab. 2007 Dec;27(12):1941-53. doi: 10.1038/sj.jcbfm.9600495. Epub 2007 Apr 18.
Cerebral ischaemia usually results in the rapid death of neurons within the immediate territory of the affected artery. Neuronal loss is accompanied by a sequence of events, including brain oedema, blood-brain barrier (BBB) breakdown, and neuroinflammation, all of which contribute to further neuronal death. Although the role of macrophages and mononuclear phagocytes in the expansion of ischaemic injury has been widely studied, the relative contribution of these cells, either of exogenous or intrinsic central nervous system (CNS) origin is still not entirely clear. The purpose of this study, therefore, was to use different durations of transient middle cerebral artery occlusion (tMCAo) in the mouse to investigate fully post-occlusion BBB permeability and cellular changes in the brain during the 72 h post-MCAo period. This was achieved using in vivo magnetic resonance imaging (MRI) and cell labelling techniques. Our results show that BBB breakdown and formation of the primary ischaemic damage after tMCAo is not associated with significant infiltration of neutrophils, although more are observed with longer periods of MCAo. In addition, we observe very few infiltrating exogenous macrophages over a 72 h period after 30 or 60 mins of occlusion, instead a profound increase in proliferating resident microglia cells was observed. Interestingly, the more severe injury associated with 60 mins of MCAo leads to a markedly reduced proliferation of resident microglial cells, suggesting that these cells may play a protective function, possibly through phagocytosis of infiltrating neutrophils. These data further support possible beneficial actions of microglial cells in the injured brain.
脑缺血通常会导致受影响动脉直接供血区域内的神经元迅速死亡。神经元丢失伴随着一系列事件，包括脑水肿、血脑屏障（BBB）破坏和神经炎症，所有这些都会导致更多神经元死亡。尽管巨噬细胞和单核吞噬细胞在缺血性损伤扩展中的作用已得到广泛研究，但这些细胞（无论是外源性还是中枢神经系统（CNS）内源性）的相对贡献仍不完全清楚。因此，本研究的目的是利用小鼠短暂性大脑中动脉闭塞（tMCAo）的不同时长，全面研究MCAo后72小时内脑内BBB通透性和细胞变化。这是通过体内磁共振成像（MRI）和细胞标记技术实现的。我们的结果表明，tMCAo后BBB破坏和原发性缺血性损伤的形成与中性粒细胞的显著浸润无关，尽管MCAo时间延长时会观察到更多中性粒细胞。此外，在闭塞30或60分钟后的72小时内，我们观察到极少的外源性巨噬细胞浸润，相反，观察到增殖的常驻小胶质细胞显著增加。有趣的是，与60分钟MCAo相关的更严重损伤导致常驻小胶质细胞的增殖明显减少，这表明这些细胞可能发挥保护作用，可能是通过吞噬浸润性中性粒细胞。这些数据进一步支持了小胶质细胞在受损大脑中可能具有的有益作用。
