Adenosine<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:msub><mml:mrow><mml:mtext>A</mml:mtext></mml:mrow><mml:mrow><mml:mtext>2A</mml:mtext></mml:mrow></mml:msub></mml:mrow></mml:math>Receptors Modulate Acute Injury and Neuroinflammation in Brain Ischemia

Pedata, Felicita; Pugliese, Anna Maria; Coppi, Elisabetta; Dettori, Ilaria; Maraula, Giovanna; Cellai, Lucrezia; Melani, Alessia

doi:10.1155/2014/805198

Cited by 57 publications

(43 citation statements)

References 202 publications

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“…The effect of glial activation on neuroinflammation and neuronal cell fate is likely to depend on specific conditions. A 2A receptor agonists reduce long-term neurologic injury after blunt spinal trauma (Reece et al, 2004), while a similar treatment improves recovery following experimental stroke (Pedata et al, 2014), in contrast to reports of the proinflammatory action of this receptor.…”

Section: The Role Of Adenosine In Neuroinflammationmentioning

confidence: 90%

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

et al. 2016

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a b s t r a c tThe principle functions of neuroinflammation are to limit tissue damage and promote tissue repair in response to pathogens or injury. While neuroinflammation has utility, pathophysiological inflammatory responses, to some extent, underlie almost all neuropathology. Understanding the mechanisms that control the three stages of inflammation (initiation, propagation and resolution) is therefore of critical importance for developing treatments for diseases of the central nervous system. The purinergic signaling system, involving adenosine, ATP and other purines, plus a host of P1 and P2 receptor subtypes, controls inflammatory responses in complex ways. Activation of the inflammasome, leading to release of pro-inflammatory cytokines, activation and migration of microglia and altered astroglial function are key regulators of the neuroinflammatory response. Here, we review the role of P1 and P2 receptors in mediating these processes and examine their contribution to disorders of the nervous system. Firstly, we give an overview of the concept of neuroinflammation. We then discuss the contribution of P2X, P2Y and P1 receptors to the underlying processes, including a discussion of cross-talk between these different pathways. Finally, we give an overview of the current understanding of purinergic contributions to neuroinflammation in the context of specific disorders of the central nervous system, with special emphasis on neuropsychiatric disorders, characterized by chronic low grade inflammation or maternal inflammation. An understanding of the important purinergic contribution to neuroinflammation underlying neuropathology is likely to be a necessary step towards the development of effective interventions.

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Section: The Role Of Adenosine In Neuroinflammationmentioning

confidence: 90%

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

et al. 2016

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“…; Pedata et al . ). Likewise, other manipulations also indicate that A 2A R activation might be neuroprotective (Huang et al .…”

Section: The Role Of A2ar In Neuroprotectionmentioning

confidence: 97%

How does adenosine control neuronal dysfunction and neurodegeneration?

Cunha

2016

Journal of Neurochemistry

366

385

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The adenosine modulation system mostly operates through inhibitory A 1 (A 1 R) and facilitatory A 2A receptors (A 2A R) in the brain. The activity-dependent release of adenosine acts as a brake of excitatory transmission through A 1 R, which are enriched in glutamatergic terminals. Adenosine sharpens salience of information encoding in neuronal circuits: highfrequency stimulation triggers ATP release in the 'activated' synapse, which is locally converted by ecto-nucleotidases into adenosine to selectively activate A 2A R; A 2A R switch off A 1 R and CB1 receptors, bolster glutamate release and NMDA receptors to assist increasing synaptic plasticity in the 'activated' synapse; the parallel engagement of the astrocytic syncytium releases adenosine further inhibiting neighboring synapses, thus sharpening the encoded plastic change. Brain insults trigger a large outflow of adenosine and ATP, as a danger signal. A 1 R are a hurdle for damage initiation, but they desensitize upon prolonged activation. However, if the insult is near-threshold and/or of short-duration, A 1 R trigger preconditioning, which may limit the spread of damage. Brain insults also up-regulate A 2A R, probably to bolster adaptive changes, but this heightens brain damage since A 2A R blockade affords neuroprotection in models of epilepsy, depression, Alzheimer's, or Parkinson's disease. This initially involves a control of synaptotoxicity by neuronal A 2A R, whereas astrocytic and microglia A 2A R might control the spread of damage. The A 2A R signaling mechanisms are largely unknown since A 2A R are pleiotropic, coupling to different G proteins and non-canonical pathways to control the viability of glutamatergic synapses, neuroinflammation, mitochondria function, and cytoskeleton dynamics. Thus, simultaneously bolstering A 1 R preconditioning and preventing excessive A 2A R function might afford maximal neuroprotection. Keywords: A 1 receptor, A 2A receptor, astrocyte, microglia, synaptic plasticity, synaptotoxicity. This article is part of a mini review series: "Synaptic Function and Dysfunction in Brain Diseases". Relevance of modulation systems to tune information flow in brain circuitsThe goal of understanding the flow of information in neuronal circuits has traditionally been centered in studying the key processes sustaining synaptic transmission and plasticity -i.e. the role of glutamate and glutamate receptors, as well as to a lesser extent the role of GABA and its receptors. If one considers an analogy to the experience of watching TV, this corresponds to studying how the ON/OFF button impacts all Received April 4, 2016; revised manuscript received May 23, 2016; accepted June 23, 2016. Address correspondence and reprint requests to R. A. Cunha, Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal. E-mail: cunharod@gmail.com Abbreviations used: A 1 R, adenosine A 1 receptor; A 2A R, adenosine A 2A receptor; ADHD, attention deficit and hyperactivity disorder; BDNF, brain-derived neurotrophi...

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“…However, even though the delivery vehicle was improved, new data suggest a temporal effect of adenosine, namely that adenosine receptors support early excitotoxicity but then seem to attenuate the inflammatory response following. 57 Regardless of this temporal finding, as technology finds new ways to deliver or improve therapies, we must be open to reassessing older agents.…”

Section: Finding New Ways To Use Old Therapies and Future Directionsmentioning

confidence: 99%

Experimental neuroprotection in ischemic stroke: a concise review

Rajah

Ding

2017

FOC

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Acute ischemic stroke (AIS) is a leading cause of disability and death worldwide. To date, intravenous tissue plasminogen activator and mechanical thrombectomy have been standards of care for AIS. There have been many advances in diagnostic imaging and endovascular devices for AIS; however, most neuroprotective therapies seem to remain largely in the preclinical phase. While many neuroprotective therapies have been identified in experimental models, none are currently used routinely to treat stroke patients. This review seeks to summarize clinical studies pertaining to neuroprotection, as well as the different preclinical neuroprotective therapies, their presumed mechanisms of action, and their future applications in stroke patients.

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AdenosineA2AReceptors Modulate Acute Injury and Neuroinflammation in Brain Ischemia

Cited by 57 publications

References 202 publications

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

How does adenosine control neuronal dysfunction and neurodegeneration?

Experimental neuroprotection in ischemic stroke: a concise review

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