The A1 receptor agonist R-Pia reduces the imbalance between cerebral glucose metabolism and blood flow during status epilepticus: Could this mechanism be involved with neuroprotection?

Silva, Iara Ribeiro; Nehlig, Astrid; Rosim, Fernanda Elisa; Vignoli, Thiago; Persike, Daniele Suzete; Ferrandon, Arielle; Sinigaglia‐Coimbra, Rita; Fernandes, Maria José da Silva

doi:10.1016/j.nbd.2010.09.004

Cited by 9 publications

(9 citation statements)

References 37 publications

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“…We have previously found that animals receiving DBS for 5 days had a significant decrease in hippocampal excitability measured in vitro with electrophysiology (Covolan et al, 2014 ). In preclinical models, the antiepileptic effects of adenosine occur largely through A1 receptors (Simonato et al, 1994 ; Ekonomou et al, 1998 ; Gouder et al, 2003 ; Rebola et al, 2003 ; Avsar and Empson, 2004 ; Mohammad-Zadeh et al, 2005 , 2009 ; Fedele et al, 2006 ; Rosim et al, 2011 ; Silva et al, 2011 ). Based on these premises, we hypothesized that the increased adenosine levels recorded after DBS might be interacting with A1 receptors to reduce hippocampal excitability.…”

Section: Resultsmentioning

confidence: 99%

Role of adenosine in the antiepileptic effects of deep brain stimulation

Miranda

Hamani

Almeida

et al. 2014

Front. Cell. Neurosci.

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Despite the effectiveness of anterior thalamic nucleus (AN) deep brain stimulation (DBS) for the treatment of epilepsy, mechanisms responsible for the antiepileptic effects of this therapy remain elusive. As adenosine modulates neuronal excitability and seizure activity in animal models, we hypothesized that this nucleoside could be one of the substrates involved in the effects of AN DBS. We applied 5 days of stimulation to rats rendered chronically epileptic by pilocarpine injections and recorded epileptiform activity in hippocampal slices. We found that slices from animals given DBS had reduced hippocampal excitability and were less susceptible to develop ictal activity. In live animals, AN DBS significantly increased adenosine levels in the hippocampus as measured by microdialysis. The reduced excitability of DBS in vitro was completely abolished in animals pre-treated with A1 receptor antagonists and was strongly potentiated by A1 receptor agonists. We conclude that some of the antiepileptic effects of DBS may be mediated by adenosine.

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Section: Resultsmentioning

confidence: 99%

Role of adenosine in the antiepileptic effects of deep brain stimulation

Miranda

Hamani

Almeida

et al. 2014

Front. Cell. Neurosci.

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“…In the present study, intrathecally administered R-PIA at a dose of 1.0–3.0 μg/10 μl also produced an antiallodynic effect in a rat model of VIPN. Considering the dose of intraperitoneal R-PIA was 20–25 μg/kg (= 4.0–6.25 μg) [ 30 , 31 ] in previous studies, the intrathecal dose of R-PIA was only 25–48% of the intraperitoneal dose of R-PIA. A smaller dose is utilized when R-PIA is administered intrathecally; therefore, side effects are reduced.…”

Section: Discussionmentioning

confidence: 99%

Antiallodynic and anti-inflammatory effects of intrathecal R-PIA in a rat model of vincristine-induced peripheral neuropathy

Kim

Jeong

Jun

et al. 2020

Korean J Anesthesiol

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Background: Studies investigating the correlation between spinal adenosine A1 receptors and vincristine-induced peripheral neuropathy (VIPN) are limited. This study explored the role of intrathecal N6-(2-phenylisopropyl)-adenosine R-(-)isomer (R-PIA) in the rat model of VIPN. Methods: Vincristine (100 μg/kg) was intraperitoneally administered for 10 days (two 5-day cycles with a 2-day pause) and VIPN was induced in rats. Pain was assessed by evaluating mechanical hyperalgesia, mechanical dynamic allodynia, thermal hyperalgesia, cold allodynia, and mechanical static allodynia. Biochemically, tumor necrosis factor-alpha (TNF-α) level and myeloperoxidase (MPO) activity were measured in the tissue from beneath the sciatic nerve.Results: Vincristine administration resulted in the development of cold allodynia, mechanical hyperalgesia, thermal hyperalgesia, mechanical dynamic allodynia, and mechanical static allodynia. Intrathecally administered R-PIA (1.0 and 3.0 μg/10 μl) reversed vincristine-induced neuropathic pain (cold and mechanical static allodynia). The attenuating effect peaked 15 min after intrathecal administration of R-PIA after which it decreased until 180 min. However, pretreatment with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 μg/10 μl) 15 min before intrathecal R-PIA administration significantly attenuated the antiallodynic effect of R-PIA. This antiallodynic effect of intrathecal R-PIA may be mediated through adenosine A1 receptors in the spinal cord. Intrathecally administered R-PIA also attenuated vincristine-induced increases in TNF-α level and MPO activity. However, pretreatment with intrathecal DPCPX significantly reversed this attenuation.Conclusions: These results suggest that intrathecally administered R-PIA attenuates cold and mechanical static allodynia in a rat model of VIPN, partially due to its anti-inflammatory actions.

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“…These effects are crucial to the intracellular Ca 2+ homeostasis maintenance mediated by A 1 receptors. In addition, injection of this A 1 receptor agonist prior to pilocarpine reduces the uncoupling between local cerebral blood flow and glucose metabolism caused by SE, resulting in neuroprotection [47].…”

Section: Neuroprotection Of Brain Areas That Are Vulnerable To Injurymentioning

confidence: 99%

Differential neuroprotection by A1 receptor activation and A2A receptor inhibition following pilocarpine-induced status epilepticus

Rosim

Persike

Nehlig

et al. 2011

Epilepsy & Behavior

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Aiming at a better understanding of the role of A(2A) in temporal lobe epilepsy (TLE), we characterized the effects of the A(2A) antagonist SCH58261 (7-(2-phenylethyl)-5-amino-2(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine) on seizures and neuroprotection in the pilocarpine model. The effects of SCH58261 were further analyzed in combination with the A(1) agonist R-Pia (R(-)-N(6)-(2)-phenylisopropyl adenosine). Eight groups were studied: pilocarpine (Pilo), SCH+Pilo, R-Pia+Pilo, R-Pia+SCH+Pilo, Saline, SCH+Saline, R-Pia+Saline, and R-Pia+SCH+Saline. The administration of SCH58261, R-Pia, and R-Pia+SCH58261 prior to pilocarpine increased the latency to SE, and decreased either the incidence of or rate of mortality from SE compared with controls. Administration of R-Pia and R-Pia+SCH58261 prior to pilocarpine reduced the number of Fluoro-Jade B-stained cells in the hippocampus and piriform cortex when compared with control. This study showed that pretreatment with R-Pia and SCH58261 reduces seizure occurrence, although only R-Pia has neuroprotective properties. Further studies are needed to clarify the neuroprotective role of A(2A) in TLE.

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The A1 receptor agonist R-Pia reduces the imbalance between cerebral glucose metabolism and blood flow during status epilepticus: Could this mechanism be involved with neuroprotection?

Cited by 9 publications

References 37 publications

Role of adenosine in the antiepileptic effects of deep brain stimulation

Role of adenosine in the antiepileptic effects of deep brain stimulation

Antiallodynic and anti-inflammatory effects of intrathecal R-PIA in a rat model of vincristine-induced peripheral neuropathy

Differential neuroprotection by A1 receptor activation and A2A receptor inhibition following pilocarpine-induced status epilepticus

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