title: Remote Limb Preconditioning Generates a Neuroprotective Effect by Modulating the Extrinsic Apoptotic Pathway and TRAIL-Receptors Expression.
abstract: As remote limb preconditioning (RPC) ameliorates brain damage after ischemic cerebral stroke (ICS), the purpose of the present study was to explore the molecular mechanisms in the course of RPC. Results of TUNEL staining and cleaved caspase-3 expression showed that ischemia-induced neuronal apoptosis was inhibited by RPC. The expression changes in cleaved caspase-8, cFLIP, Bid itself, and its truncated form represented that RPC suppressed the activation of extrinsic apoptotic pathway during ICS. Then, the level of cytoplasmic cytochrome c was also decreased by RPC. In addition, RPC might partially suppress TNF-related apoptosis-inducing ligand (TRAIL)-induced extrinsic apoptosis through downregulation of TRAIL death receptors and upregulation of TRAIL decoy receptors. As a counterproof, immunoneutralization of TRAIL in dMCAO rats resulted in significant restraint of tissue damage and in a marked functional recovery. Our data complemented the knowledge of RPC neuroprotective mechanism and provided new evidence for its clinical application.
authors.affiliation: Department of Neurology, Shanghai No. 5 Hospital, Fudan University, No. 801 Heqing Road, Shanghai, 200240, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Neurology, Shanghai No. 5 Hospital, Fudan University, No. 801 Heqing Road, Shanghai, 200240, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.affiliation: Department of Neurology, Shanghai No. 5 Hospital, Fudan University, No. 801 Heqing Road, Shanghai, 200240, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Shanghai No. 5 Hospital, Fudan University, No. 801 Heqing Road, Shanghai, 200240, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurology, Shanghai No. 5 Hospital, Fudan University, No. 801 Heqing Road, Shanghai, 200240, China. rccnsf@sina.com.
authors.forename: Chuancheng
authors.initials: C
authors.lastname: Ren
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism* / Q000517:prevention & control; D005121:Extremities / Q000098:blood supply; D005263:Femoral Artery / Q000378:metabolism*; D005786:Gene Expression Regulation; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D018696:Neuroprotective Agents / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018696:Neuroprotective Agents; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand
keywords: Ischemic cerebral stoke; Neuronal apoptosis; Remote limb preconditioning; TRAIL-receptors