Pharmacology and Toxicology Department, University of Puerto Rico, Medical Sciences Campus, Guillermo Arbona, Área de Centro Médico Río Piedras, PR 00935, USA.
Department of Physiology, Universidad Central del Caribe Ave. Laurel #100, Santa Juanita, Bayamón, PR 00956, USA.
Biomolecules. 2019 Aug 8;9(8):350. doi: 10.3390/biom9080350.
It is well known that amyloid beta (Aβ) peptides are generated in blood vessels, released into the brain during thrombosis, and temporarily accumulate in this organ after injury. Here we demonstrate that 24 h after transient middle cerebral artery occlusion (tMCAO), one of the standard models of focal ischemic stroke, Aβ peptide accumulates in the brain, concentrating on the blood vessel walls. Because Aβ oligomers are known to induce significant damage to brain cells, they act as an additional damaging factor during ischemic stroke. Considering that they have been shown to form ion channels in cells, affecting osmotic balance, we used an Aβ peptide channel blocker, tromethamine (2-amino-2-(hydroxymethyl) propane-1,3-diol), to prevent this additional injury. Tromethamine injected 0.1 g/100 g body weight intraperitoneally at 5 min before tMCAO decreased water content in the damaged hemisphere, as measured by dry brain weight. Congo red staining, which binds only to Aβ oligomer plaques (amyloid), showed that there was no significant presence of plaques. Therefore, we suggest that Aβ peptide oligomers are responsible for some of the brain damage during stroke and that blockage of the ion channels that they form could be beneficial in treating this complex neurological syndrome.
众所周知，淀粉样β（Aβ）肽在血管中生成，在血栓形成过程中释放到大脑中，并在受伤后暂时积聚在该器官中。在这里，我们证明在短暂性大脑中动脉闭塞（tMCAO）后 24 小时，作为局灶性缺血性中风标准模型之一，Aβ肽积聚在大脑中，集中在血管壁上。因为已知 Aβ寡聚体对脑细胞有很大的损伤作用，所以它们在缺血性中风期间作为额外的损伤因素。考虑到它们已被证明在细胞中形成离子通道，影响渗透平衡，我们使用 Aβ肽通道阻滞剂三羟甲基氨基甲烷（2-氨基-2-（羟甲基）丙烷-1,3-二醇）来防止这种额外的损伤。在 tMCAO 前 5 分钟，以 0.1 g/100 g 体重的剂量腹腔内注射三羟甲基氨基甲烷，可通过干脑重测量来降低受损半球的含水量。仅与 Aβ寡聚体斑块（淀粉样）结合的刚果红染色表明没有明显的斑块存在。因此，我们认为 Aβ肽寡聚体是中风期间部分脑损伤的原因，阻断它们形成的离子通道可能对治疗这种复杂的神经综合征有益。
