Activation of Alpha-7 Nicotinic Acetylcholine Receptor Reduces Brain Edema in Mice with Ischemic Stroke and Bone Fracture

Zou, Dingquan; Luo, Man; Han, Zhaoxia; Zhan, Lei; Zhu, Wan; Kang, Shuai; Bao, Chunyan; Zhao, Li; Nelson, Jeffrey; Zhang, Rui; Su, Hua

doi:10.1007/s12035-016-0310-8

Cited by 27 publications

(28 citation statements)

References 49 publications

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“… 14 Following cerebral ischemia, several preclinical studies have observed that both the local upregulation and the pharmacological activation of nicotinic receptors protects the brain against ischemic injury, suggesting the protective central cholinergic effect and the potential role of these receptors as promising inflammatory biomarkers. 15 – 23 …”

Section: Cholinergic Receptorsmentioning

confidence: 99%

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Inflammation in stroke: the role of cholinergic, purinergic and glutamatergic signaling

Martín

Domercq

Matute

2018

Ther Adv Neurol Disord

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The inflammatory response is a major factor in stroke pathophysiology and contributes to secondary neuronal damage in both acute and chronic stages of the ischemic injury. Recent work in experimental cerebral ischemia has demonstrated the involvement of neurotransmitter signaling in the modulation of neuroinflammation. The present review discusses recent findings on the therapeutic potential and diagnostic perspectives of cholinergic, purinergic and glutamatergic receptors and transporters in experimental stroke. It provides evidence of the role of neurotransmission signaling as a promising inflammatory biomarker in stroke. Finally, recent molecular imaging studies using positron emission tomography of cholinergic receptors and glutamatergic transporters are outlined along with their potential as novel anti-inflammatory therapy to reduce the outcome of cerebral ischemia.

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Section: Cholinergic Receptorsmentioning

confidence: 99%

“… 22 In contrast, Zou and colleagues examined the effect of α7 nAChRs activation with PHA after cerebral ischemia in mice showing an improvement of the BBB integrity. 16 …”

Section: Cholinergic Receptorsmentioning

confidence: 99%

Inflammation in stroke: the role of cholinergic, purinergic and glutamatergic signaling

Martín

Domercq

Matute

2018

Ther Adv Neurol Disord

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“…16 We found in our previous studies that tibia fracture occurring either before or after pMCAO exacerbates infarct sizes and sensorimotor dysfunction. [20][21][22][23] However, the impact of BF on post-stroke cognitive function has not been studied.…”

Section: Introductionmentioning

confidence: 99%

Fracture shortly before stroke in mice leads to hippocampus inflammation and long-lasting memory dysfunction

Wei

Lyu

et al. 2019

J Cereb Blood Flow Metab

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Cognitive impairment occurs in stroke and hip fracture patients. In mice, bone fracture (BF) exacerbates stroke-related neuronal damage and sensorimotor dysfunction. We hypothesize that BF exacerbates post-stroke cognitive impairment. Adult mice were randomly assigned into BF, stroke, BF+stroke (BF 6 h before stroke), and control (sham operated) groups. Memory function was evaluated weekly for eight weeks by Y maze test and at eight weeks post-surgeries by novel object recognition (NOR) test. The neuronal damage and inflammation in hippocampus were analyzed three days and eight weeks after the surgeries. In Y maze test, BF+stroke mice started making fewer alternations than controls two weeks after the surgeries. Significant difference between BF+stroke and stroke groups started at five weeks post-injury and continued to the end of the experiment. In NOR test, BF+stroke group spent less time on novel objective than that of other groups. Cx3cr1+ cells and CD68+ cells accumulated in the stratum lacunosum moleculare (SLM) on the ipsilateral side of stroke injury in stroke and BF+stroke mice. BF+stroke mice had a higher ratio of ipsilateral/contralateral Cx3cr1+ cell-density than that of stroke mice. Therefore, BF shortly before stroke exacerbates hippocampal inflammation and causes long-lasting memory dysfunction.

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“…Pharmacological activation of α7 nAChRs with the agonist PHA 568487 has previously shown the reduction of brain edema, ischemic stroke injury, neuroinflammation and oxidative stress following ischemic stroke in mice (Han, Li, et al, ; Han, Shen, et al, ; Zou et al, ). In our study, we explored the effect of PHA on brain edema with T 2 W‐MRI and neuroinflammation by using in vivo [ 18 F]DPA‐714 PET binding following cerebral ischemia (Figure ).…”

Section: Discussionmentioning

confidence: 99%

In vivo imaging of Α7 nicotinic receptors as a novel method to monitor neuroinflammation after cerebral ischemia

Colás

Domercq

Ramos‐Cabrer

et al. 2018

Glia

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In vivo positron emission tomography (PET) imaging of nicotinic acetylcholine receptors (nAChRs) is a promising tool for the imaging evaluation of neurologic and neurodegenerative diseases. However, the role of α7 nAChRs after brain diseases such as cerebral ischemia and its involvement in inflammatory reaction is still largely unknown. In vivo and ex vivo evaluation of α7 nAChRs expression after transient middle cerebral artery occlusion (MCAO) was carried out using PET imaging with [ C]NS14492 and immunohistochemistry (IHC). Pharmacological activation of α7 receptors was evaluated with magnetic resonance imaging (MRI), [ F]DPA-714 PET, IHC, real time polymerase chain reaction (qPCR) and neurofunctional studies. In the ischemic territory, [ C]NS14492 signal and IHC showed an expression increase of α7 receptors in microglia and astrocytes after cerebral ischemia. The role played by α7 receptors on neuroinflammation was supported by the decrease of [ F]DPA-714 binding in ischemic rats treated with the α7 agonist PHA 568487 at day 7 after MCAO. Moreover, compared with non-treated MCAO rats, PHA-treated ischemic rats showed a significant reduction of the cerebral infarct volumes and an improvement of the neurologic outcome. PHA treatment significantly reduced the expression of leukocyte infiltration molecules in MCAO rats and in endothelial cells after in vitro ischemia. Despite that, the activation of α7 nAChR had no influence to the blood brain barrier (BBB) permeability measured by MRI. Taken together, these results suggest that the nicotinic α7 nAChRs play a key role in the inflammatory reaction and the leukocyte recruitment following cerebral ischemia in rats.

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Activation of Alpha-7 Nicotinic Acetylcholine Receptor Reduces Brain Edema in Mice with Ischemic Stroke and Bone Fracture

Cited by 27 publications

References 49 publications

Inflammation in stroke: the role of cholinergic, purinergic and glutamatergic signaling

Inflammation in stroke: the role of cholinergic, purinergic and glutamatergic signaling

Fracture shortly before stroke in mice leads to hippocampus inflammation and long-lasting memory dysfunction

In vivo imaging of Α7 nicotinic receptors as a novel method to monitor neuroinflammation after cerebral ischemia

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