Long-term survival and regeneration of neuronal and vasculature cells inside the core region after ischemic stroke in adult mice.
Long-term survival and regeneration of neuronal and vasculature cells inside the core region after ischemic stroke in adult mice.
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DOI：
10.1111/bpa.12425
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发表时间：
2017-07
期刊：
影响因子：
--
通讯作者：
Yu SP
中科院分区：
文献类型：
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作者：
Jiang MQ;Zhao YY;Cao W;Wei ZZ;Gu X;Wei L;Yu SP
局灶性脑缺血导致被梗塞周围区域（半影）包围的缺血核心。大多数研究关注的是半暗带，而缺血核心内的细胞命运模式定义不清。在目前的调查中，我们测试的假设，在缺血的核心，一些神经元和血管细胞可以生存的初始缺血性损伤，而再生壁龛可能存在中风后许多天在成年人的大脑。采用永久性阻断大脑中动脉（MCA）远端分支加短暂性结扎双侧颈总动脉（CCA）的方法，对成年小鼠进行局灶性脑缺血。缺血性损伤使局部脑血流量（LCBF）均匀减少90%。由于多种机制发生大量细胞死亡，24小时后在缺血皮质中培养出显著的梗塞。然而，正常或甚至更高水平的脑源性神经营养因子（BDNF）和血管内皮生长因子（VEGF）持续存在于核心组织中，一些NeuN阳性和Glut-1/College IV阳性细胞具有完整的超微结构特征，驻留在卒中后7-14天的核心。BrdU阳性，但TUNEL阴性的神经元和内皮细胞中检测到广泛的细胞外基质基础设施的核心。同时，GFAP阳性的星形胶质细胞聚集在半影区和Iba-1阳性的小胶质细胞/巨噬细胞侵入核心中风后几天。在MCA永久性栓塞闭塞引起的严重缺血性卒中后，也观察到缺血核心内神经元和血管细胞的长期存活。我们证明，药物低温的治疗干预可以保存核心内的神经元/内皮细胞。这些数据表明，缺血性核心是一个积极调节的大脑区域，在至少某些类型的缺血性中风后，急性和慢性存在残留和新形成的存活神经元和血管细胞。
Focal cerebral ischemia results in an ischemic core surrounded by the peri-infarct region (penumbra). Most research attention has been focused on penumbra while the pattern of cell fates inside the ischemic core is poorly defined. In the present investigation, we tested the hypothesis that, inside the ischemic core, some neuronal and vascular cells could survive the initial ischemic insult while regenerative niches might exist many days after stroke in the adult brain. Adult mice were subjected to focal cerebral ischemia induced by permanent occlusion of distal branches of the middle cerebral artery (MCA) plus transient ligations of bilateral common carotid artery (CCA). The ischemic insult uniformly reduced the local cerebral blood flow (LCBF) by 90%. Massive cell death occurred due to multiple mechanisms and a significant infarction was cultivated in the ischemic cortex 24 hrs later. Nevertheless, normal or even higher levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) persistently remained in the core tissue, some NeuN-positive and Glut-1/College IV-positive cells with intact ultrastructural features resided in the core 7–14 days post stroke. BrdU-positive but TUNEL-negative neuronal and endothelial cells were detected in the core where extensive extracellular matrix infrastructure developed. Meanwhile, GFAP-positive astrocytes accumulated in the penumbra and Iba-1-positive microglial/macrophages invaded the core several days after stroke. The long survival of neuronal and vascular cells inside the ischemic core was also seen after a severe ischemic stroke induced by permanent embolic occlusion of the MCA. We demonstrate that a therapeutic intervention of pharmacological hypothermia could save neurons/endothelial cells inside the core. These data suggest that the ischemic core is an actively regulated brain region with residual and newly formed viable neuronal and vascular cells acutely and chronically after at least some types of ischemic strokes.