Pichardo-Rojas Diego, Pichardo-Rojas Pavel Salvador, Cornejo-Bravo José Manuel, Serrano-Medina Aracely
Facultad de Medicina y Psicología, Universidad Autónoma de Baja California, Tijuana, Mexico.
Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center at Houston, Houston, TX, United States.
Front Neurosci. 2023 Jan 19;17:1096372. doi: 10.3389/fnins.2023.1096372. eCollection 2023.
The primary mechanism for neuron death after an ischemic stroke is excitotoxic injury. Excessive depolarization leads to NMDA-mediated calcium entry to the neuron and, subsequently, cellular death. Therefore, the inhibition of the NMDA channel has been proposed as a neuroprotective measure in ischemic stroke. The high morbimortality associated with stroke warrants new therapies that can improve the functional prognosis of patients. Memantine is a non-competitive NMDA receptor antagonist which has gained attention as a potential drug for ischemic stroke. Here we analyze the available preclinical and clinical evidence concerning the use of memantine following an ischemic stroke. Preclinical evidence shows inhibition of the excitotoxic cascade, as well as improved outcomes in terms of motor and sensory function with the use of memantine. The available clinical trials of high-dose memantine in patients poststroke have found that it can improve patients' NIHSS and Barthel index and help patients with poststroke aphasia and intracranial hemorrhage. These results suggest that memantine has a clinically relevant neuroprotective effect; however, small sample sizes and other study shortcomings limit the impact of these findings. Even so, current studies show promising results that should serve as a basis to promote future research to conclusively determine if memantine does improve the outcomes of patients' post-ischemic stroke. We anticipate that future trials will fill current gaps in knowledge, and these latter results will broaden the therapeutic arsenal for clinicians looking to improve the prognosis of patients poststroke.
缺血性中风后神经元死亡的主要机制是兴奋性毒性损伤。过度去极化导致NMDA介导的钙离子进入神经元，随后导致细胞死亡。因此，抑制NMDA通道已被提议作为缺血性中风的一种神经保护措施。与中风相关的高病残率和死亡率促使人们寻求新的疗法来改善患者的功能预后。美金刚是一种非竞争性NMDA受体拮抗剂，作为一种潜在的缺血性中风治疗药物受到了关注。在此，我们分析了有关缺血性中风后使用美金刚的现有临床前和临床证据。临床前证据表明，美金刚可抑制兴奋性毒性级联反应，并改善运动和感觉功能。现有的关于中风后患者使用高剂量美金刚的临床试验发现，它可以改善患者的美国国立卫生研究院卒中量表（NIHSS）评分和巴氏指数，并有助于治疗中风后失语症和颅内出血患者。这些结果表明美金刚具有临床相关的神经保护作用；然而，小样本量和其他研究缺陷限制了这些发现的影响力。即便如此，目前的研究显示出有前景的结果，这些结果应作为促进未来研究的基础，以最终确定美金刚是否确实能改善缺血性中风患者的预后。我们预计未来的试验将填补当前的知识空白，而这些结果将为希望改善中风后患者预后的临床医生拓宽治疗手段。
