title: Molecular dialogs between the ischemic brain and the peripheral immune system: dualistic roles in injury and repair.
abstract: Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialog between the brain and peripheral immune system show promise as potential novel treatments for stroke.
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Chengrui
authors.initials: C
authors.lastname: An
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Fudan University, Shanghai 200032, China; 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 15240, USA.
authors.forename: Yejie
authors.initials: Y
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Fudan University, Shanghai 200032, China; 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 Institutes of Brain Science, Fudan University, Shanghai 200032, China; 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 15240, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Fudan University, Shanghai 200032, China; 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 Institutes of Brain Science, Fudan University, Shanghai 200032, China; 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 15240, USA.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Stetler
authors.affiliation: Division of Pharmaceutical Sciences, 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 Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Key Laboratory of Cerebral Microcirculation in Universities of Shandong (Taishan Medical University), Department of Neurology, Affiliated Hospital of Taishan Medical University, Taian, Shandong 271000, China. Electronic address: blsun88@163.com.
authors.forename: Bao-Liang
authors.initials: BL
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Fudan University, Shanghai 200032, China. Electronic address: pzheng@shmu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Fudan University, Shanghai 200032, China; 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 15240, USA. Electronic address: chenj2@upmc.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000276:immunology* / Q000503:physiopathology; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications* / Q000175:diagnosis* / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000276:immunology* / Q000503:physiopathology; D007249:Inflammation / Q000209:etiology*
chemical_list: D016207:Cytokines
keywords: Brain repair; Cerebral ischemic injury; Inflammation; Innate immunity