Brassai A, Suvanjeiev R-G, Bán E-Gy, Lakatos M
Department of Pharmacology, University of Medicine and Pharmacy, Târgu Mureş, Romania.
1st Clinic of Psychiatry, University of Medicine and Pharmacy, Târgu Mureş, Romania.
Brain Res Bull. 2015 Mar;112:1-6. doi: 10.1016/j.brainresbull.2014.12.007. Epub 2014 Dec 23.
In acute ischaemic brain injury and chronic neurodegeneration, the first step leading to excitotoxicity and cell death is the excessive release of Glu and the prolonged activation of Glu receptors, followed by intracellular calcium overload. There is apparent agreement that glutamatergic transmission via synaptic NMDA receptors (composed of GluN2A subunits) is neuroprotective, whereas transmission via non-synaptic NMDA receptors (composed of GluN2B subunits) is excitotoxic. Extrasynaptic NMDARs activate cell death pathways and may play a key role in Glu-induced excitotoxic neurodegeneration and apoptosis. Accordingly, the function of protective pathways may be impaired by the concomitant blockade of GluN2A-containing receptors. In contrast, the selective inhibition of non-synaptic GluN2B-containing NMDARs may be beneficial in neuroprotection because it can prevent neuronal cell death and thus maintain protective pathways.
在急性缺血性脑损伤和慢性神经退行性变中，导致兴奋性毒性和细胞死亡的第一步是谷氨酸（Glu）的过度释放和Glu受体的长时间激活，随后是细胞内钙超载。目前普遍认为，通过突触N-甲基-D-天冬氨酸（NMDA）受体（由GluN2A亚基组成）的谷氨酸能传递具有神经保护作用，而通过非突触NMDA受体（由GluN2B亚基组成）的传递则具有兴奋性毒性。突触外NMDAR激活细胞死亡途径，可能在Glu诱导的兴奋性毒性神经退行性变和细胞凋亡中起关键作用。因此，含GluN2A受体的同时阻断可能会损害保护途径的功能。相比之下，选择性抑制含非突触GluN2B的NMDAR可能对神经保护有益，因为它可以防止神经元细胞死亡，从而维持保护途径。
