Ischemic stroke is the main cause of disability and mortality in the world. Clinical studies have shown that patients who undergo mild transient ischemic attack (TIA) before more severe ischemic stroke have lower clinical severity of stroke and better functional prognosis. This phenomenon is called ischemic preconditioning (IPC). IPC is a powerful intrinsic protection of the brain against ischemic injury, but the underlying mechanism of IPC-mediated endogenous protection of the brain is not clear. METHODS: Using transcriptome method, we sequenced the serum of 3 stroke patients with progenitor TIA and 3 stroke patients without prodromal TIA. We explored the expression profiles of miRNAs and mRNAs in response to IPC, and predicted the regulatory pathway of IPC related genes and their expression in cerebral neurons. The methylation consistent expression of IPC-related gene ATP2B1 in blood and brain and alternative polyadenylate (APA) analysis were used to identify the pathway and molecular mechanism of endogenous neuroprotection of IPC. RESULTS: We found that the brain protective effect of IPC was related to platelet homeostasis and Ca2+ concentration. IPC-related gene ATP2B1 was highly expressed in γ-aminobutyric acid (GABA)-containing neurons in the brain. From the mechanism, we speculated that ATP2B1 was representative of the same methylation in blood and brain and was affected by alternative polyadenylation. CONCLUSION: We speculate that IPC can induce alternative polyadenylation of ATP2B1 and trigger the mechanism of brain endogenous neuroprotection by regulating the decrease of Ca2+ concentration in platelet homeostasis pathway and the activation of GABAB receptor. AJTR
Ischemic stroke is the main cause of disability and mortality in the world. Clinical studies have shown that patients who undergo mild transient ischemic attack (TIA) before more severe ischemic stroke have lower clinical severity of stroke and better functional prognosis. This phenomenon is called ischemic preconditioning (IPC). IPC is a powerful intrinsic protection of the brain against ischemic injury, but the underlying mechanism of IPC-mediated endogenous protection of the brain is not clear. METHODS: Using transcriptome method, we sequenced the serum of 3 strokepatients with progenitor TIA and 3 strokepatients without prodromal TIA. We explored the expression profiles of miRNAs and mRNAs in response to IPC, and predicted the regulatory pathway of IPC related genes and their expression in cerebral neurons. The methylation consistent expression of IPC-related gene ATP2B1 in blood and brain and alternative polyadenylate (APA) analysis were used to identify the pathway and molecular mechanism of endogenous neuroprotection of IPC. RESULTS: We found that the brain protective effect of IPC was related to platelet homeostasis and Ca2+ concentration. IPC-related gene ATP2B1 was highly expressed in γ-aminobutyric acid (GABA)-containing neurons in the brain. From the mechanism, we speculated that ATP2B1 was representative of the same methylation in blood and brain and was affected by alternative polyadenylation. CONCLUSION: We speculate that IPC can induce alternative polyadenylation of ATP2B1 and trigger the mechanism of brain endogenous neuroprotection by regulating the decrease of Ca2+ concentration in platelet homeostasis pathway and the activation of GABAB receptor. AJTR
Authors: Ana I Casas; Pamela Wm Kleikers; Eva Geuss; Friederike Langhauser; Thure Adler; Dirk H Busch; Valerie Gailus-Durner; Martin Hrabê de Angelis; Javier Egea; Manuela G Lopez; Christoph Kleinschnitz; Harald Hhw Schmidt Journal: J Clin Invest Date: 2019-03-18 Impact factor: 14.808
Authors: Rebecca D Hodge; Trygve E Bakken; Jeremy A Miller; Kimberly A Smith; Eliza R Barkan; Lucas T Graybuck; Jennie L Close; Brian Long; Nelson Johansen; Osnat Penn; Zizhen Yao; Jeroen Eggermont; Thomas Höllt; Boaz P Levi; Soraya I Shehata; Brian Aevermann; Allison Beller; Darren Bertagnolli; Krissy Brouner; Tamara Casper; Charles Cobbs; Rachel Dalley; Nick Dee; Song-Lin Ding; Richard G Ellenbogen; Olivia Fong; Emma Garren; Jeff Goldy; Ryder P Gwinn; Daniel Hirschstein; C Dirk Keene; Mohamed Keshk; Andrew L Ko; Kanan Lathia; Ahmed Mahfouz; Zoe Maltzer; Medea McGraw; Thuc Nghi Nguyen; Julie Nyhus; Jeffrey G Ojemann; Aaron Oldre; Sheana Parry; Shannon Reynolds; Christine Rimorin; Nadiya V Shapovalova; Saroja Somasundaram; Aaron Szafer; Elliot R Thomsen; Michael Tieu; Gerald Quon; Richard H Scheuermann; Rafael Yuste; Susan M Sunkin; Boudewijn Lelieveldt; David Feng; Lydia Ng; Amy Bernard; Michael Hawrylycz; John W Phillips; Bosiljka Tasic; Hongkui Zeng; Allan R Jones; Christof Koch; Ed S Lein Journal: Nature Date: 2019-08-21 Impact factor: 49.962