单克隆抗体作为急性缺血性脑卒中的新疗法。

International journal of physiology, pathophysiology and pharmacology Pub Date : 2020-08-25 eCollection Date: 2020-01-01
Demi Woods, Qian Jiang, Xiang-Ping Chu
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引用次数: 0

摘要

急性缺血性中风(AIS)是美国第五大死亡原因和神经功能障碍的主要原因。AIS相关的缺氧和葡萄糖剥夺不仅导致神经元细胞死亡,还会增加炎症反应,从而降低脑功能结局。美国联邦食品和药物管理局唯一批准用于治疗AIS的药物干预是组织纤溶酶原激活剂(t-PA),然而,这种治疗只能在中风样症状出现后4.5小时内给予。这种狭窄的时间范围限制了它的治疗应用。在治疗窗口外给予t-PA可能对中风患者产生有害而非有益的影响。为了在增加治疗时间的同时减少AIS的梗死面积,新的治疗方法是必不可少的。新兴的单克隆抗体(mAb)疗法通过靶向AIS后激活的信号通路显示出巨大的潜力。随着单抗在癌症治疗中的成功应用,目前正在评估单抗的其他治疗用途。在这篇综述中,我们将重点介绍利用mAb靶向信号级联和内源性分子(如炎症、生长因子、酸敏感离子通道和n -甲基- d-天冬氨酸受体)治疗AIS的最新进展。因此,开发针对缺血性脑损伤信号通路的特异性单克隆抗体将有利于AIS患者的治疗。
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Monoclonal antibody as an emerging therapy for acute ischemic stroke.

Acute ischemic stroke (AIS) is the 5th leading cause of death and the leading cause of neurological disability in the United States. The oxygen and glucose deprivation associated with AIS not only leads to neuronal cell death, but also increases the inflammatory response, therefore decreasing the functional outcome of the brain. The only pharmacological intervention approved by the US Federal Food and Drug Administration for treatment of AIS is tissue plasminogen activator (t-PA), however, such treatment can only be given within 4.5 hours of the onset of stroke-like symptoms. This narrow time-range limits its therapeutic application. Administrating t-PA outside of the therapeutic window may induce detrimental rather than beneficial effects to stroke patients. In order to reduce the infarct volume of an AIS while increasing the time period for treatment, new treatments are essential. Emerging monoclonal antibody (mAb) therapies reveal great potential by targeting signaling pathways activated after an AIS. With successful application of mAb in the treatment of cancer, other therapeutic uses for mAb are currently being evaluated. In this review, we will focus on recent advances on AIS therapy by using mAb that targets the signaling cascades and endogenous molecules such as inflammation, growth factors, acid-sensing ion channels, and N-methyl-D-aspartate receptors. Therefore, developing specific mAb to target the signaling pathways of ischemic brain injury will benefit patients being treated for an AIS.

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