PDF(Pubmed)
Abstract：
Translation of neuroprotective treatment effects from experimental animal models to patients with cerebral ischemia has been challenging. Since pathophysiological processes may vary across species, an experimental model to clarify human-specific neuronal pathomechanisms may help. We conducted a scoping review of the literature on human neuronal in vitro models that have been used to study neuronal responses to ischemia or hypoxia, the parts of the pathophysiological cascade that have been investigated in those models, and evidence on effects of interventions. We included 147 studies on four different human neuronal models. The majority of the studies (132/147) was conducted in SH-SY5Y cells, which is a cancerous cell line derived from a single neuroblastoma patient. Of these, 119/132 used undifferentiated SH-SY5Y cells, that lack many neuronal characteristics. Two studies used healthy human induced pluripotent stem cell derived neuronal networks. Most studies used microscopic measures and established hypoxia induced cell death, oxidative stress, or inflammation. Only one study investigated the effect of hypoxia on neuronal network functionality using micro-electrode arrays. Treatment targets included oxidative stress, inflammation, cell death, and neuronal network stimulation. We discuss (dis)advantages of the various model systems and propose future perspectives for research into human neuronal responses to ischemia or hypoxia.
摘要：
将神经保护性治疗作用从实验动物模型转化为脑缺血患者一直具有挑战性。由于病理生理过程可能因物种而异，阐明人类特异性神经元病理机制的实验模型可能会有所帮助。我们对已用于研究缺血或缺氧的神经元反应的人神经元体外模型的文献进行了范围综述。在这些模型中研究的病理生理级联的部分，以及干预效果的证据。我们纳入了对四种不同人类神经元模型的147项研究。大多数研究（132/147）是在SH-SY5Y细胞中进行的，这是一种来源于单个神经母细胞瘤患者的癌细胞系。其中,119/132使用未分化的SH-SY5Y细胞，缺乏许多神经元特征。两项研究使用健康人诱导多能干细胞衍生的神经元网络。大多数研究使用微观措施和建立缺氧诱导的细胞死亡，氧化应激，或炎症。只有一项研究使用微电极阵列研究了缺氧对神经元网络功能的影响。治疗目标包括氧化应激，炎症,细胞死亡,和神经元网络刺激。我们讨论了各种模型系统的（缺点）优势，并提出了研究人类神经元对缺血或缺氧的反应的未来观点。
