Woods Demi, Jiang Qian, Chu Xiang-Ping
Department of Biomedical Sciences, School of Medicine, University of Missouri-Kansas City Kansas City, MO 64108, USA.
Int J Physiol Pathophysiol Pharmacol. 2020 Aug 25;12(4):95-106. eCollection 2020.
Acute ischemic stroke (AIS) is the 5 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.
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。与AIS相关的氧和葡萄糖剥夺不仅会导致神经元细胞死亡,还会增加炎症反应,从而降低大脑的功能预后。美国联邦食品药品监督管理局批准的用于治疗AIS的唯一药物干预是组织纤溶酶原激活剂(t-PA),然而,这种治疗只能在出现中风样症状后的4.5小时内进行。这个狭窄的时间范围限制了其治疗应用。在治疗窗口之外使用t-PA可能会对中风患者产生有害而非有益的影响。为了减少AIS的梗死体积并延长治疗时间,新的治疗方法至关重要。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潜力。随着mAb在癌症治疗中的成功应用,目前正在评估mAb的其他治疗用途。在这篇综述中,我们将重点关注使用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)的mAb在AIS治疗方面的最新进展。因此,开发针对缺血性脑损伤信号通路的特异性mAb将使接受AIS治疗的患者受益。