Department of Pharmacology, Medical School, University of Zagreb, Zagreb, Croatia.
Department of Pathology, Medical School, University of Zagreb, Zagreb, Croatia.
Brain Behav. 2020 Aug;10(8):e01726. doi: 10.1002/brb3.1726. Epub 2020 Jun 18.
We focused on the, yet undescribed, therapy effect of the stable gastric pentadecapeptide BPC 157 in hippocampal ischemia/reperfusion injuries, after bilateral clamping of the common carotid arteries in rats. The background is the proven therapy effect of BPC 157 in ischemia/reperfusion injuries in different tissues. Furthermore, there is the subsequent oxidative stress counteraction, particularly when given during reperfusion. The recovering effect it has on occluded vessels, results with activation of the alternative pathways, bypassing the occlusion in deep vein thrombosis. Finally, the BPC 157 therapy benefits with its proposed role as a novel mediator of Roberts' cytoprotection and bidirectional effects in the gut-brain axis.
Male Wistar rats underwent bilateral clamping of the common carotid arteries for a 20-min period. At 30 s thereafter, we applied medication (BPC 157 10 µg/kg; or saline) as a 1 ml bath directly to the operated area, that is, trigonum caroticum. We documented, in reperfusion, the resolution of the neuronal damages sustained in the brain, resolution of the damages reflected in memory, locomotion, and coordination disturbances, with the presentation of the particular genes expression in hippocampal tissues.
In the operated rats, at 24 and 72 hr of the reperfusion, the therapy counteracted both early and delayed neural hippocampal damage, achieving full functional recovery (Morris water maze test, inclined beam-walking test, lateral push test). mRNA expression studies at 1 and 24 hr, provided strongly elevated (Egr1, Akt1, Kras, Src, Foxo, Srf, Vegfr2, Nos3, and Nos1) and decreased (Nos2, Nfkb) gene expression (Mapk1 not activated), as a way how BPC 157 may act.
Together, these findings suggest that these beneficial BPC 157 effects may provide a novel therapeutic solution for stroke.
我们专注于研究稳定的胃十五肽 BPC 157 在大鼠双侧颈总动脉夹闭后的海马缺血/再灌注损伤中的治疗作用,这种作用在不同组织的缺血/再灌注损伤中已经得到了证实。此外,BPC 157 在再灌注期间还具有随后的抗氧化应激作用。它对闭塞血管的恢复作用是通过激活替代途径来实现的,从而绕过深静脉血栓形成中的闭塞。最后,BPC 157 的治疗作用得益于其作为罗伯茨细胞保护作用的新型介质的作用,以及在肠-脑轴中的双向作用。
雄性 Wistar 大鼠行双侧颈总动脉夹闭 20 分钟。夹闭 30 秒后,我们将药物(BPC 157 10µg/kg;或生理盐水)以 1ml 浴液直接应用于手术区域,即颈动脉三角。我们记录了再灌注时大脑中神经元损伤的恢复情况,记忆、运动和协调障碍的恢复情况,以及海马组织中特定基因表达的情况。
在手术大鼠中,再灌注后 24 和 72 小时,治疗方法拮抗了早期和晚期的海马神经损伤,实现了完全的功能恢复(Morris 水迷宫测试、斜梁行走测试、侧向推测试)。1 小时和 24 小时的 mRNA 表达研究提供了强烈升高(Egr1、Akt1、Kras、Src、Foxo、Srf、Vegfr2、Nos3 和 Nos1)和降低(Nos2、Nfkb)的基因表达(Mapk1 未被激活),这是 BPC 157 可能作用的一种方式。
综上所述,这些发现表明,这些有益的 BPC 157 作用可能为中风提供一种新的治疗解决方案。