title: Preconditioning provides neuroprotection in models of CNS disease: paradigms and clinical significance.
abstract: Preconditioning is a phenomenon in which brief episodes of a sublethal insult induce robust protection against subsequent lethal injuries. Preconditioning has been observed in multiple organisms and can occur in the brain as well as other tissues. Extensive animal studies suggest that the brain can be preconditioned to resist acute injuries, such as ischemic stroke, neonatal hypoxia/ischemia, surgical brain injury, trauma, and agents that are used in models of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Effective preconditioning stimuli are numerous and diverse, ranging from transient ischemia, hypoxia, hyperbaric oxygen, hypothermia and hyperthermia, to exposure to neurotoxins and pharmacological agents. The phenomenon of "cross-tolerance," in which a sublethal stress protects against a different type of injury, suggests that different preconditioning stimuli may confer protection against a wide range of injuries. Research conducted over the past few decades indicates that brain preconditioning is complex, involving multiple effectors such as metabolic inhibition, activation of extra- and intracellular defense mechanisms, a shift in the neuronal excitatory/inhibitory balance, and reduction in inflammatory sequelae. An improved understanding of brain preconditioning should help us identify innovative therapeutic strategies that prevent or at least reduce neuronal damage in susceptible patients. In this review, we focus on the experimental evidence of preconditioning in the brain and systematically survey the models used to develop paradigms for neuroprotection, and then discuss the clinical potential of brain preconditioning.
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai Medical College, Shanghai 200032, China; Department of Neurology and Center of Cerebrovascular Disease Research, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213, USA; Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261, USA.
authors.forename: R Anne
authors.initials: RA
authors.lastname: Stetler
authors.affiliation: Division of Pharmaceutical Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA 15282, USA.
authors.forename: Rehana K
authors.initials: RK
authors.lastname: Leak
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai Medical College, Shanghai 200032, China; Department of Neurology and Center of Cerebrovascular Disease Research, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gan
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai Medical College, Shanghai 200032, China; Department of Neurology and Center of Cerebrovascular Disease Research, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Peiying
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai Medical College, Shanghai 200032, China; Department of Neurology and Center of Cerebrovascular Disease Research, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213, USA; Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Neurology and Center of Cerebrovascular Disease Research, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213, USA; Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Neurology and Center of Cerebrovascular Disease Research, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213, USA; Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Jing
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai Medical College, Shanghai 200032, China; Department of Neurology and Center of Cerebrovascular Disease Research, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213, USA; Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai Medical College, Shanghai 200032, China; Department of Neurology and Center of Cerebrovascular Disease Research, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zigmond
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai Medical College, Shanghai 200032, China. Electronic address: yqgao@shmu.edu.cn.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000818:Animals; D002493:Central Nervous System Diseases / Q000628:therapy*; D004195:Disease Models, Animal; D006801:Humans; D019194:Ischemic Preconditioning; D018696:Neuroprotective Agents / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents
keywords: Ischemia; Neuroprotection; Preconditioning; Traumatic brain injury