The role of potassium BK channels in anticonvulsant effect of cannabidiol in pentylenetetrazole and maximal electroshock models of seizure in mice

Shirazi-zand, Zahra; Ahmad-Molaei, Leila; Motamedi, Fereshteh; Naderi, Nima

doi:10.1016/j.yebeh.2013.03.009

Cited by 65 publications

(36 citation statements)

References 76 publications

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“…Again, these changes are normalized by paxilline (Mehranfard et al, 2014). Importantly, BK channel blockade does not exert an anticonvulsant effect in animals that had no previous seizure experience, and even reduces the protective effect of cannabidiol in a first seizure episode (Sheehan et al, 2009; Shirazi-zand, Ahmad-Molaei, Motamedi, & Naderi, 2013). …”

Section: Role Of Bk Channels In Cns Function and Pathologiesmentioning

confidence: 99%

BK Channels in the Central Nervous System

Contet

Goulding

Kuljis

et al. 2016

International Review of Neurobiology

143

170

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Large conductance Ca2+- and voltage-activated K+ (BK) channels are widely distributed in the postnatal central nervous system (CNS). BK channels play a pleiotropic role in regulating the activity of brain and spinal cord neural circuits by providing a negative feedback mechanism for local increases in intracellular Ca2+ concentrations. In neurons, they regulate the timing and duration of K+ influx such that they can either increase or decrease firing depending on the cellular context, and they can suppress neurotransmitter release from presynaptic terminals. In addition, BK channels located in astrocytes and arterial myocytes modulate cerebral blood flow. Not surprisingly, both loss and gain of BK channel function have been associated with CNS disorders such as epilepsy, ataxia, mental retardation, and chronic pain. On the other hand, the neuroprotective role played by BK channels in a number of pathological situations could potentially be leveraged to correct neurological dysfunction.

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Section: Role Of Bk Channels In Cns Function and Pathologiesmentioning

confidence: 99%

BK Channels in the Central Nervous System

Contet

Goulding

Kuljis

et al. 2016

International Review of Neurobiology

143

170

View full text Add to dashboard Cite

show abstract

“…Cannabidiol (Tocris, UK) was dissolved in a mixture of dimethylsulfoxide (DMSO; 10%) and phosphate buffer solution (PBS, 90%) (Shirazi-zand, Ahmad-Molaei, Motamedi, & Naderi, 2013). Microinjection of cannabidiol into right lateral ventricle was in a volume of 2 μL.…”

Section: Methodsmentioning

confidence: 99%

“…Microinjection of cannabidiol into right lateral ventricle was in a volume of 2 μL. ICV injection of cannabidiol at doses of 50, 100, and 200 ng/rat (Shirazi-zand et al, 2013) was given by inserting a 30-gauge injection cannula 1 mm beyond the tip of the guide cannula to the site of injection. The injection cannula was connected with a polyethylene tube to a Hamilton syringe.…”

Section: Methodsmentioning

confidence: 99%

Correlation Between Cannabidiol-Induced Reduction of Infarct Volume and Inflammatory Factors Expression in Ischemic Stroke Model

Bigdeli

2017

BCN

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Introduction:Recent studies demonstrated that cannabidiol had neuroprotective property. There is some evidence about effective role of cannabidiol in reduction of ischemic damages. It has been reported that infarct size is influenced by various factors after MCAO, including inflammatory factors. The aim of the present study was to evaluate the effect of cannabidiol on infarction volume and correlation of infarct size with tumor necrosis factor receptor 1 (TNFR1), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression.Methods:Using stereotaxic surgery, guide cannula was implanted in the right lateral ventricle. Cannabidiol (50, 100, and 200 ng/rat) was injected through ntracerebroventricular (i.c.v.) route for 5 consecutive days . Then, the rats underwent 60 minutes of right middle cerebral artery occlusion (MCAO). After 24 h reperfusion, the infarct volume in total, cortex, piriform cortex-amygdala (Pir-Amy), and striatum areas of hemisphere were assessed. The expression of inflammatory factors such as TNFR1 and NF-κB in these regions were also studied.Results:The present results indicate that in the MCAO-induced cerebral ischemia, administration of cannabidiol (100 and 200 ng/rat) causes a significant reduction in infarction volume in comparison with the vehicle group. Also, there were significant correlations between decrease of regional infarct volume and TNFR1/NF-κB expression.Conclusion:The results of this study indicate that cannabidiol reduced cerebral infarction possibly through diminishing TNFR1/NF-κB-induced neurotoxicity in transient focal cerebral ischemia.

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“…13 In vivo, treating rats with CBD before pentylenetetrazole administration, increases the amount of pentylenetetrazole required to initiate a seizure, reduces the incidence of tonic-clonic seizures, and decreases mortality. 13,14 In an SCN1A knockout mouse model of Dravet syndrome, treatment with CBD decreased the number of spontaneous seizures as well as the duration and severity of thermallyinduced seizures. Autistic-like social interaction deficits improved with low dose CBD but, interestingly, not with the higher dose of CBD required for seizure control.…”

Section: Preclinical Antiepileptic Trialsmentioning

confidence: 99%

Efficacy of cannabinoids in paediatric epilepsy

Ali

Scheffer

Sadleir

2018

Develop Med Child Neuro

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There are hundreds of compounds found in the marijuana plant, each contributing differently to the antiepileptic and psychiatric effects. Cannabidiol (CBD) has the most evidence of antiepileptic efficacy and does not have the psychoactive effects of ∆9‐tetrahydrocannabinol. CBD does not act via cannabinoid receptors and its antiepileptic mechanism of action is unknown. Despite considerable community interest in the use of CBD for paediatric epilepsy, there has been little evidence for its use apart from anecdotal reports, until the last year. Three randomized, placebo‐controlled, double‐blind trials in Dravet syndrome and Lennox–Gastaut syndrome found that CBD produced a 38% to 41% median reduction in all seizures compared to 13% to 19% on placebo. Similarly, CBD resulted in a 39% to 46% responder rate (50% convulsive or drop‐seizure reduction) compared to 14% to 27% on placebo. CBD was well tolerated; however, sedation, diarrhoea, and decreased appetite were frequent. CBD shows similar efficacy to established antiepileptic drugs. What this paper adds Cannabidiol (CBD) shows similar efficacy in the severe paediatric epilepsies to other antiepileptic drugs. Careful down‐titration of benzodiazepines is essential to minimize sedation with adjunctive CBD.

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The role of potassium BK channels in anticonvulsant effect of cannabidiol in pentylenetetrazole and maximal electroshock models of seizure in mice

Cited by 65 publications

References 76 publications

BK Channels in the Central Nervous System

BK Channels in the Central Nervous System

Correlation Between Cannabidiol-Induced Reduction of Infarct Volume and Inflammatory Factors Expression in Ischemic Stroke Model

Efficacy of cannabinoids in paediatric epilepsy

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