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Prog Neurobiol. 2014 Apr;115:6-24. doi: 10.1016/j.pneurobio.2013.12.002. Epub 2013 Dec 26.

Molecular dialogs between the ischemic brain and the peripheral immune system: dualistic roles in injury and repair.

Author information

1
State Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
2
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.
3
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.
4
Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA.
5
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.
6
State Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Fudan University, Shanghai 200032, China. Electronic address: pzheng@shmu.edu.cn.
7
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.

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.

KEYWORDS:

Brain repair; Cerebral ischemic injury; Inflammation; Innate immunity

PMID:
24374228
PMCID:
PMC4014303
DOI:
10.1016/j.pneurobio.2013.12.002
[Indexed for MEDLINE]
Free PMC Article

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