Boosting Endogenous Resistance of Brain to Ischemia

Sun, Feng-Yan; Johnson, Stephen R.; Jin, Kunlin; Uteshev, Victor V.

doi:10.1007/s12035-016-9796-3

Cited by 14 publications

(30 citation statements)

References 69 publications

(170 reference statements)

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“…In contrast, blockade of α7nAChRs with the selective antagonist, methyllycaconitine, increased infarct size, suggesting some degree of α7 stimulation by endogenous agonist (Han et al 2014). Other investigators have suggested that endogenous choline that is released from injured brain tissue might fill this role (Sun et al, 2013a; Sun et al, 2017). These investigators found that treatment with PNU-120596, an allosteric modulator of α7nAChRs, decreased infarct size and improved performance on several neurological tests when given 6 h after transient occlusion of the middle cerebral artery in mice (Sun et al, 2013a).…”

Section: Targeting α7nachrs On Microglia and Macrophages In Strokementioning

confidence: 99%

“…These investigators found that treatment with PNU-120596, an allosteric modulator of α7nAChRs, decreased infarct size and improved performance on several neurological tests when given 6 h after transient occlusion of the middle cerebral artery in mice (Sun et al, 2013a). Subsequent work demonstrated that intranasal administration of PNU-120596 had similar therapeutic efficacy using the same stoke model in rats (Sun et al, 2017).…”

Section: Targeting α7nachrs On Microglia and Macrophages In Strokementioning

confidence: 99%

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Cholinergic modulation of the immune system presents new approaches for treating inflammation

Hoover

2017

Pharmacology & Therapeutics

244

169

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The nervous system and immune system have broad and overlapping distributions in the body, and interactions of these ubiquitous systems are central to the field of neuroimmunology. Over the past two decades, there has been explosive growth in our understanding of neuroanatomical, cellular, and molecular mechanisms that mediate central modulation of immune functions through the autonomic nervous system. A major catalyst for growth in this field was the discovery that vagal nerve stimulation (VNS) caused a prominent attenuation of the systemic inflammatory response evoked by endotoxin in experimental animals. This effect was mediated by acetylcholine (ACh) stimulation of nicotinic receptors on splenic macrophages. Hence, the circuit was dubbed the “cholinergic anti-inflammatory pathway”. Subsequent work identified the α7 nicotinic ACh receptor (α7nAChR) as the crucial target for attenuation of pro-inflammatory cytokine release from macrophages and dendritic cells. Further investigation made the important discovery that cholinergic T cells within the spleen and not cholinergic nerve cells were the source of ACh that stimulated α7 receptors on splenic macrophages. Given the important role that inflammation plays in numerous disease processes, cholinergic anti-inflammatory mechanisms are under intensive investigation from a basic science perspective and in translational studies of animal models of diseases such as inflammatory bowel disease and rheumatoid arthritis. This basic work has already fostered several clinical trials examining the efficacy of VNS and cholinergic therapeutics in human inflammatory diseases. This review provides an overview of basic and translational aspects of the cholinergic anti-inflammatory response and relevant pharmacology of drugs acting at the α7nAChR.

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Section: Targeting α7nachrs On Microglia and Macrophages In Strokementioning

confidence: 99%

Section: Targeting α7nachrs On Microglia and Macrophages In Strokementioning

confidence: 99%

Cholinergic modulation of the immune system presents new approaches for treating inflammation

Hoover

2017

Pharmacology & Therapeutics

244

169

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“…Acetylcholine, via nicotinic receptors (nAChRs), is involved in hypoxic or ischaemic preconditioning in the brain and other organs, and this is most convincingly demonstrated for the homomeric α7 nAChRs [18][19][20][21]. The preconditioning (as well as postconditioning) α7 nAChRs effects are closely related to neuronal adaptive and neuroimmune antiinflammatory mechanisms in which α7 nAChRs are particularly important in protecting against hypoxic damage in peripheral organs [22][23][24][25] and the central nervous system [19,20,22,[26][27][28].…”

Section: Introductionmentioning

confidence: 99%

The Acoustic Sensorimotor Gating Predicts the Efficiency of Hypoxic Preconditioning. Participation of the Cholinergic System in This Phenomenon

Захарова¹,

Сторожева²,

Proshin³

et al. 2018

JBiSE

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Moderate one-off hypobaric hypoxia (HBH) provokes preconditioning and prolongs the resistance (T, the time before apnoea) to severe hypobaric hypoxia (SHBH). Hypoxic preconditioning has therapeutic potential; however, the efficiency of hypoxic preconditioning varies greatly and the methods for its preliminary evaluation are absent in both animals and humans. This rodent study evaluates the dependence of SHBH resistance, initiated by HBH, on the rate of sensorimotor gating estimated in the model of the acoustic startle prepulse inhibition (PPI). A stable negative correlation was found between PPI and T. Low doses of the α7 nicotinic receptor agonist, PNU-282987 (PNU), and more pronouncedly dimethyl sulfoxide (DMSO) (a PNU solvent), inverted the correlation between PPI and T from negative to positive. The DMSO and PNU effects were reversed at PPIs of 0.36 -0.40 (36% -40%). DMSO increased T values by 52.2% ± 9.7% in the region of lower HBH efficiency (PPI ≥ 0.40) and reduced it by 35.2% ± 9.3% in the region of higher HBH efficiency (PPI < 0.40). PNU reduced both DMSO effects. The involvement of the central cholinergic mechanisms was substantiated in both DMSO and PNU influences on HBH. In conclusion, 1) PPI can be used to predict the efficiency of hypoxic preconditioning and to study its mechanisms, 2) two opposite cholinergic PPI-related mechanisms participate in the preconditioning effects of HBH, 3) the sensitivity of rats to DMSO and PNU diverges when the PPI is 0.36 -0.40,

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“…The endogenous choline released from damaged brain tissue may fulfil this role. The use of an allosteric modulator of α7nAChRs 6 h after tMCAO can reduce the infarct volume and improve neurological performance [231, 232]. In addition, regulation of α7nAChRs has also been shown to be associated with changes in M1 and M2 microglia/macrophages after CI [229].…”

Section: Introductionmentioning

confidence: 99%

The spleen may be an important target of stem cell therapy for stroke

Wang

Zeng

et al. 2019

J Neuroinflammation

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Stroke is the most common cerebrovascular disease, the second leading cause of death behind heart disease and is a major cause of long-term disability worldwide. Currently, systemic immunomodulatory therapy based on intravenous cells is attracting attention. The immune response to acute stroke is a major factor in cerebral ischaemia (CI) pathobiology and outcomes. Over the past decade, the significant contribution of the spleen to ischaemic stroke has gained considerable attention in stroke research. The changes in the spleen after stroke are mainly reflected in morphology, immune cells and cytokines, and these changes are closely related to the stroke outcomes. Autonomic nervous system (ANS) activation, release of central nervous system (CNS) antigens and chemokine/chemokine receptor interactions have been documented to be essential for efficient brain-spleen cross-talk after stroke. In various experimental models, human umbilical cord blood cells (hUCBs), haematopoietic stem cells (HSCs), bone marrow stem cells (BMSCs), human amnion epithelial cells (hAECs), neural stem cells (NSCs) and multipotent adult progenitor cells (MAPCs) have been shown to reduce the neurological damage caused by stroke. The different effects of these cell types on the interleukin (IL)-10, interferon (IFN), and cholinergic anti-inflammatory pathways in the spleen after stroke may promote the development of new cell therapy targets and strategies. The spleen will become a potential target of various stem cell therapies for stroke represented by MAPC treatment.

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Boosting Endogenous Resistance of Brain to Ischemia

Cited by 14 publications

References 69 publications

Cholinergic modulation of the immune system presents new approaches for treating inflammation

Cholinergic modulation of the immune system presents new approaches for treating inflammation

The Acoustic Sensorimotor Gating Predicts the Efficiency of Hypoxic Preconditioning. Participation of the Cholinergic System in This Phenomenon

The spleen may be an important target of stem cell therapy for stroke

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