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Adenosine A2A receptor blockade attenuates excitotoxicity in rat striatal medium spiny neurons during an ischemic-like insult

Coppi, Elisabetta; Cherchi, Federica; Gibb, Alasdair J; (2024) Adenosine A2A receptor blockade attenuates excitotoxicity in rat striatal medium spiny neurons during an ischemic-like insult. Neural Regeneration Research , 19 (2) pp. 255-257. 10.4103/1673-5374.375309. Green open access

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Abstract

During brain ischemia, excitotoxicity and peri-infarct depolarization injuries occur and cause cerebral tissue damage. Indeed, anoxic depolarization, consisting of massive neuronal depolarization due to the loss of membrane ion gradients, occurs in vivo or in vitro during an energy failure. The neuromodulator adenosine is released in huge amounts during cerebral ischemia and exerts its effects by activating specific metabotropic receptors, namely: A1, A2A, A2B, and A3. The A2A receptor subtype is highly expressed in striatal medium spiny neurons, which are particularly susceptible to ischemic damage. Evidence indicates that the A2A receptors are upregulated in the rat striatum after stroke and the selective antagonist SCH58261 protects from exaggerated glutamate release within the first 4 hours from the insult and alleviates neurological impairment and histological injury in the following 24 hours. We recently added new knowledge to the mechanisms by which the adenosine A2A receptor subtype participates in ischemia-induced neuronal death by performing patch-clamp recordings from medium spiny neurons in rat striatal brain slices exposed to oxygen and glucose deprivation. We demonstrated that the selective block of A2A receptors by SCH58261 significantly reduced ionic imbalance and delayed the anoxic depolarization in medium spiny neurons during oxygen and glucose deprivation and that the mechanism involves voltage-gated K+ channel modulation and a presynaptic inhibition of glutamate release by the A2A receptor antagonist. The present review summarizes the latest findings in the literature about the possibility of developing selective ligands of A2A receptors as advantageous therapeutic tools that may contribute to counteracting neurodegeneration after brain ischemia.

Type: Article
Title: Adenosine A2A receptor blockade attenuates excitotoxicity in rat striatal medium spiny neurons during an ischemic-like insult
Location: India
Open access status: An open access version is available from UCL Discovery
DOI: 10.4103/1673-5374.375309
Publisher version: https://doi.org/10.4103/1673-5374.375309
Language: English
Additional information: This is an open access journal, and articles are distributed under the terms of the Creative Commons AttributionNonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
Keywords: adenosine A2A, anoxic depolarization, brain ischemia, glutamate excitotoxicity, medium spiny neurons, oxygen and glucose deprivation, receptors
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10174923
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