Neuroinflammation, Stroke, Blood-Brain Barrier Dysfunction, and Imaging Modalities.
Neuroinflammation, Stroke, Blood-Brain Barrier Dysfunction, and Imaging Modalities.
复制标题
神经炎，中风，血脑屏障功能障碍，和成像方式。
作者：
维持血脑屏障（BBB）完整性对于中枢神经系统（CNS）的稳态至关重要。脑内皮细胞在结构上包括 BBB，与神经血管单元 (NVU) 中的周细胞、星形胶质细胞、神经元、小胶质细胞和血管周围巨噬细胞相互作用。脑缺血会引发严重的神经炎症反应，以清除受损组织并为大脑修复做好准备。然而，中风急性期发生的强烈神经炎症与血脑屏障破坏、神经元损伤和更差的神经系统结果有关。在这里，我们批判性地讨论神经炎症在缺血性中风病理学中的作用，重点关注血脑屏障以及中枢神经系统和外周免疫反应之间的相互作用。我们强调中风中炎症驱动的损伤机制，包括氧化应激、基质金属蛋白酶产生增加、小胶质细胞激活以及外周免疫细胞浸润到缺血组织中。我们提供了体内检测缺血性脑损伤后血脑屏障通透性、白细胞浸润、小胶质细胞激活和细胞粘附分子上调的成像技术的最新概述。我们讨论了临床实施成像方式来评估中风相关神经炎症的可能性，并有可能提供图像引导的诊断和治疗。我们总结了几项评估抗炎干预措施对中风疗效的临床研究的结果。尽管令人信服的临床前证据表明神经炎症是缺血性中风的一个有希望的目标，但迄今为止，将这些结果转化为临床环境已被证明是困难的。由于炎症在缺血性损伤进展中的双重作用，需要更多的研究来从机制上理解神经炎症反应何时开始从损伤到修复的转变。通过为特定时间和特定环境的治疗干预提供信息，这可能对缺血性中风治疗产生重要影响。
Maintaining blood-brain barrier (BBB) integrity is crucial for the homeostasis of the central nervous system (CNS). Structurally comprising the BBB, brain endothelial cells interact with pericytes, astrocytes, neurons, microglia, and perivascular macrophages in the neurovascular unit (NVU). Brain ischemia unleashes a profound neuroinflammatory response to remove the damaged tissue and prepare the brain for repair. However, the intense neuroinflammation occurring during the acute phase of stroke is associated with BBB breakdown, neuronal injury, and worse neurological outcomes. Here, we critically discuss the role of neuroinflammation in ischemic stroke pathology, focusing on the BBB and the interactions between CNS and peripheral immune responses. We highlight inflammation-driven injury mechanisms in stroke, including oxidative stress, increased matrix metalloproteinase production, microglial activation, and infiltration of peripheral immune cells into the ischemic tissue. We provide an updated overview of imaging techniques for in vivo detection of BBB permeability, leukocyte infiltration, microglial activation, and upregulation of cell adhesion molecules following ischemic brain injury. We discuss the possibility of clinical implementation of imaging modalities to assess stroke-associated neuroinflammation with the potential to provide image-guided diagnosis and treatment. We summarize the results from several clinical studies evaluating the efficacy of anti-inflammatory interventions in stroke. Although convincing preclinical evidence suggests that neuroinflammation is a promising target for ischemic stroke, thus far, translating these results into the clinical setting has proved difficult. Due to the dual role of inflammation in the progression of ischemic damage, more research is needed to mechanistically understand when the neuroinflammatory response begins the transition from injury to repair. This could have important implications for ischemic stroke treatment by informing time- and context-specific therapeutic interventions.
DOI：
10.1038/jcbfm.2013.22
发表时间：
2013-05
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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