Exogenous adenosine facilitates neuroprotection and functional recovery following cerebral ischemia in rats

Seydyousefi, Mehdi; Moghanlou, Abdorreza Eghbal; Metz, Gerlinde A. S.; Gürsoy, Recep; Faghfoori, Mohammad Hasan; Mirghani, Seyed Javad; Faghfoori, Zeinab

doi:10.1016/j.brainresbull.2019.09.010

Cited by 19 publications

(7 citation statements)

References 53 publications

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“…One of the reasons for the non-parallel changes in adenosine and adenosine A1R after cordycepin treatment may be related to the desensitization of A1R because A1R was prone to rapid desensitization in the presence of a high dose of adenosine (Von Lubitz et al, 1995). In addition, there was no significant change in the level of A2AR in the cordycepin group after GCI, which seemed to contradict the previous report that the level of A2AR increases accompanied with the supplement of exogenous adenosine in the hippocampal CA1 area after temporary cerebral ischemia (Seydyousefi et al, 2019). We speculated that the rapid increase of adenosine in the short term was maybe not enough to change the level of A2AR.…”

Section: Discussioncontrasting

confidence: 66%

Cordycepin Ameliorates Synaptic Dysfunction and Dendrite Morphology Damage of Hippocampal CA1 via A1R in Cerebral Ischemia

Chen

Han

Shang

et al. 2021

Front. Cell. Neurosci.

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Cordycepin exerted significant neuroprotective effects and protected against cerebral ischemic damage. Learning and memory impairments after cerebral ischemia are common. Cordycepin has been proved to improve memory impairments induced by cerebral ischemia, but its underlying mechanism has not been revealed yet. The plasticity of synaptic structure and function is considered to be one of the neural mechanisms of learning and memory. Therefore, we investigated how cordycepin benefits dendritic morphology and synaptic transmission after cerebral ischemia and traced the related molecular mechanisms. The effects of cordycepin on the protection against ischemia were studied by using global cerebral ischemia (GCI) and oxygen-glucose deprivation (OGD) models. Behavioral long-term potentiation (LTP) and synaptic transmission were observed with electrophysiological recordings. The dendritic morphology and histological assessment were assessed by Golgi staining and hematoxylin-eosin (HE) staining, respectively. Adenosine A1 receptors (A1R) and adenosine A2A receptors (A2AR) were evaluated with western blotting. The results showed that cordycepin reduced the GCI-induced dendritic morphology scathing and behavioral LTP impairment in the hippocampal CA1 area, improved the learning and memory abilities, and up-regulated the level of A1R but not A2AR. In the in vitro experiments, cordycepin pre-perfusion could alleviate the hippocampal slices injury and synaptic transmission cripple induced by OGD, accompanied by increased adenosine content. In addition, the protective effect of cordycepin on OGD-induced synaptic transmission damage was eliminated by using an A1R antagonist instead of A2AR. These findings revealed that cordycepin alleviated synaptic dysfunction and dendritic injury in ischemic models by modulating A1R, which provides new insights into the pharmacological mechanisms of cordycepin for ameliorating cognitive impairment induced by cerebral ischemia.

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Section: Discussioncontrasting

confidence: 66%

Cordycepin Ameliorates Synaptic Dysfunction and Dendrite Morphology Damage of Hippocampal CA1 via A1R in Cerebral Ischemia

Chen

Han

Shang

et al. 2021

Front. Cell. Neurosci.

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“…Adenosine is an important neuromodulator, which not only regulates Alzheimer's disease, Parkinson's disease, epilepsy, inflammation, cancer, and other diseases but also alleviates the injuries caused by cerebral ischemia and reperfusion [ 18 ]. Previous studies had shown that exogenous injection of adenosine could upregulate the expression of A2A receptor in hippocampal cells after cerebral ischemia and reperfusion in rats, thus reducing the death of neurons in the hippocampal CA1 region and promoting the recovery of sensorimotor function [ 19 ]. Ganesana and Venton monitored release of adenosine during cerebral ischemia and reperfusion.…”

Section: Discussionmentioning

confidence: 99%

Metabonomics Study on Naotaifang Extract Alleviating Neuronal Apoptosis after Cerebral Ischemia-Reperfusion Injury

Chen

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Naotaifang extract (NTE) is a clinically effective traditional Chinese medicine compound for cerebral ischemia-reperfusion injury. Although NTE can achieve neuroprotective function through different mechanisms, the pharmacodynamic substances of NTE corresponding to these mechanisms have rarely been reported. Alleviating or inhibiting neuronal apoptosis is an important way to achieve neuroprotection. Accordingly, this study has evaluated the effects of NTE on alleviating neuronal apoptosis after cerebral ischemia-reperfusion injury from two levels of cells and tissues. Meanwhile, the serum pharmacochemistry of NTE was analyzed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) with the guidance of Chinmedomics. The results included three aspects: (1) NTE could significantly alleviate neuronal apoptosis caused by in vitro cellular models and in vivo animal models; (2) a total of 21 serum differential metabolites was discovered, including adenosine, inosine, ferulic acid, calycosin, salidroside, 6-gingerol, 2-methoxycinnamaldehyde, and so on; (3) the metabolic pathway regulated by NTE was mainly purine metabolism. From these results, it can be concluded that alleviating neuronal apoptosis by NTE after cerebral ischemia-reperfusion injury is one of the important mechanisms to achieve neuroprotection. The pharmacodynamic substances of NTE for alleviating neuronal apoptosis on the one hand are related to components directly absorbed into blood, such as ferulic acid, calycosin, salidroside, 6-gingerol, and 2-methoxycinnamaldehyde and on the other hand are also closely linked to its indirect regulation of purine metabolism in the body to produce adenosine and inosine. Therefore, our research not only identified the main pharmacodynamic substances of NTE that alleviated neuronal apoptosis but also provided a methodological reference for studying other neuroprotective effects of NTE.

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“…It is hypothesized that in the brain, ATP released from the pre- and post-synaptic terminals of neurons and glial cells is the source of extracellular adenosine [ 94 ]. In the extracellular area, adenosine is produced from ATP after dephosphorylation by specific ectoenzymes, in this case, CD39 and CD73, expressed in microglial cells [ 90 ].…”

Section: The Role Of Adenosine In Glioblastoma Multiformementioning

confidence: 99%

Adenosine Targeting as a New Strategy to Decrease Glioblastoma Aggressiveness

Bova

Filippone

Casili

et al. 2022

Cancers

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Glioblastoma is the most commonly malignant and aggressive brain tumor, with a high mortality rate. The role of the purine nucleotide adenosine and its interaction with its four subtypes receptors coupled to the different G proteins, A1, A2A, A2B, and A3, and its different physiological functions in different systems and organs, depending on the active receptor subtype, has been studied for years. Recently, several works have defined extracellular adenosine as a tumoral protector because of its accumulation in the tumor microenvironment. Its presence is due to both the interaction with the A2A receptor subtype and the increase in CD39 and CD73 gene expression induced by the hypoxic state. This fact has fueled preclinical and clinical research into the development of efficacious molecules acting on the adenosine pathway and blocking its accumulation. Given the success of anti-cancer immunotherapy, the new strategy is to develop selective A2A receptor antagonists that could competitively inhibit binding to its endogenous ligand, making them reliable candidates for the therapeutic management of brain tumors. Here, we focused on the efficacy of adenosine receptor antagonists and their enhancement in anti-cancer immunotherapy.

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Exogenous adenosine facilitates neuroprotection and functional recovery following cerebral ischemia in rats

Cited by 19 publications

References 53 publications

Cordycepin Ameliorates Synaptic Dysfunction and Dendrite Morphology Damage of Hippocampal CA1 via A1R in Cerebral Ischemia

Cordycepin Ameliorates Synaptic Dysfunction and Dendrite Morphology Damage of Hippocampal CA1 via A1R in Cerebral Ischemia

Metabonomics Study on Naotaifang Extract Alleviating Neuronal Apoptosis after Cerebral Ischemia-Reperfusion Injury

Adenosine Targeting as a New Strategy to Decrease Glioblastoma Aggressiveness

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