Hypoxia/ischemia a key player in early post stroke seizures: Modulation by opioidergic and nitrergic systems

Gooshe, Maziar; Abdolghaffari, Amir Hossein; Aleyasin, Ali Reza; Chabouk, Leila; Tofigh, Sina; Hassanzadeh, Gholam Reza; Payandemehr, Borna; Partoazar, Alireza; Azizi, Yaser; Dehpour, Ahmad Reza

doi:10.1016/j.ejphar.2014.11.005

Cited by 27 publications

(14 citation statements)

References 69 publications

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“…Therefore, this study demonstrates that iNOS plays an important role in the induction of neuronal apoptosis following brain ischemia‐reperfusion injury, and suggest that appropriate iNOS inhibitors could be used as a neuroprotective agent to reduce the severity of cerebral ischemia in the clinic in the near future. This was also demonstrated by Gooshe et al, (), whose study showed that aminoguanidine (a potent iNOS inhibitor) could reverse post stroke ischemic insult.…”

Section: Discussionsupporting

confidence: 66%

Effects and Mechanism of Action of Inducible Nitric Oxide Synthase on Apoptosis in a Rat Model of Cerebral Ischemia‐Reperfusion Injury

Zheng

Ding

Wang

et al. 2015

The Anatomical Record

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Inducible nitric oxide synthase (iNOS) is a key enzyme in regulating nitric oxide (NO) synthesis under stress, and NO has varying ability to regulate apoptosis. The aim of this study was to investigate the effects and possible mechanism of action of iNOS on neuronal apoptosis in a rat model of cerebral focal ischemia and reperfusion injury in rats treated with Smethylisothiourea sulfate (SMT), a high-selective inhibitor of iNOS. Seventytwo male Sprague-Dawley (SD) rats were randomly divided into three groups: the sham, middle cerebral artery occlusion (MCAO) 1 vehicle, and MCAO 1 SMT groups. Neurobehavioral deficits, infarct zone size, and cortical neuron morphology were evaluated through the modified Garcia scores, 2,3,5-triphenyltetrazolium chloride (TTC), and Nissl staining, respectively. Brain tissues and serum samples were collected at 72 hr post-reperfusion for immunohistochemical analysis, Western blotting, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin Nick End Labeling assay (TUNEL) staining, and enzyme assays. The study found that inhibition of iNOS significantly attenuated the severity of the pathological changes observed as a result of ischemia-reperfusion injury: SMT reduced NO content as well as total nitric oxide synthase (tNOS) and iNOS activities in both ischemic cerebral hemisphere and serum, improved neurobehavioral scores, reduced mortality, reduced the infarct volume ratio, attenuated morphological changes in cortical neurons, decreased the rate of apoptosis (TUNEL and caspase-3-positive), and increased phospho (p)-AKT expression in ischemic penumbra. These results suggested that inhibition of iNOS might reduce the severity of ischemia-reperfusion injury by inhibiting neuronal apoptosis via maintaining p-AKT activity. Anat Rec, 299:246-255, 2016. V C 2015 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 66%

Effects and Mechanism of Action of Inducible Nitric Oxide Synthase on Apoptosis in a Rat Model of Cerebral Ischemia‐Reperfusion Injury

Zheng

Ding

Wang

et al. 2015

The Anatomical Record

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“…Cerebral blood flow studies have revealed both cerebral hypoperfusion and hyperperfusion [2,32] with evidence of angiographic vasospasm and vasculopathy predominantly affecting the posterior circulation and watershed regions [33]. In our cohort, although both the parietal and occipital lobes were involved with equal frequency, there was a greater proportion of seizures from occipital lobe involvement likely from its inherent "selective vulnerability" coupled with hypoperfusion from PRES resulting in hypoxia, a well-known mechanism of seizures [34,35]. Besides the location, the occurrence of PRES-related seizures was independent of involvement of the cerebral cortex and the presence of hemorrhage and number of affected lobes, which is also different when compared to seizures from other vascular etiologies [28,29].…”

Section: Discussionmentioning

confidence: 96%

Predictors of seizures in patients with posterior reversible encephalopathy syndrome

Hinduja

Habetz

Raina

et al. 2016

Epilepsy & Behavior

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“…Seizure is one of the most important side effects of opioids, and several studies have suggested the possible involvement of the opioidergic system in epileptogenesis . It was reported that the activation of µ‐opioid receptors in the central nervous system can have excitatory and proconvulsive effects.…”

Section: Discussionmentioning

confidence: 99%

Methadone's effects on pentylenetetrazole‐induced seizure threshold in mice: NMDA/opioid receptors and nitric oxide signaling

Roodsari

Bahramnejad

Rahimi

et al. 2019

Annals of the New York Academy of Sciences

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Methadone is a synthetic opioid used to treat opiate withdrawal and addiction. Studies have demonstrated the impact of methadone on seizure susceptibility. This study investigated the modulatory impacts of acute and subchronic (three times daily for 5 days) intraperitoneal methadone treatment on pentylenetetrazole‐induced clonic seizure threshold (CST) in mice, as well as the involvement of the nitric oxide, N‐methyl‐d‐aspartate (NMDA), and µ‐opioid pathways. Acute administration of different doses of methadone (0.1, 0.3, 1, and 3 mg/kg) 45 min before CST significantly decreased the seizure threshold. Additionally, pretreatment with noneffective doses of an opioid receptor antagonist (naltrexone) and NMDA receptor antagonists (ketamine and MK‐801) inhibited methadone's proconvulsive activity in the acute phase, while l‐NAME (a nonspecific nitric oxide synthase (NOS) inhibitor) did not affect that activity. In the subchronic phase, methadone (3 mg/kg) demonstrated an anticonvulsive effect. Although subchronic pretreatment with noneffective doses of l‐NAME and 7‐nitroindazole (a specific neuronal NOS inhibitor) reversed methadone's anticonvulsive activity, aminoguanidine (a specific inducible NOS inhibitor), naltrexone, MK‐801, and ketamine did not change methadone's anticonvulsive characteristic. Our results suggest that NMDA and µ‐opioid receptors may be involved in methadone's proconvulsive activity in the acute phase, while methadone's anticonvulsive activity may be modulated by neuronal NOS in the subchronic phase.

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Hypoxia/ischemia a key player in early post stroke seizures: Modulation by opioidergic and nitrergic systems

Cited by 27 publications

References 69 publications

Effects and Mechanism of Action of Inducible Nitric Oxide Synthase on Apoptosis in a Rat Model of Cerebral Ischemia‐Reperfusion Injury

Effects and Mechanism of Action of Inducible Nitric Oxide Synthase on Apoptosis in a Rat Model of Cerebral Ischemia‐Reperfusion Injury

Predictors of seizures in patients with posterior reversible encephalopathy syndrome

Methadone's effects on pentylenetetrazole‐induced seizure threshold in mice: NMDA/opioid receptors and nitric oxide signaling

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