Anti-excitotoxic effects of cannabidiol are partly mediated by enhancement of NCX2 and NCX3 expression in animal model of cerebral ischemia

Bigdeli, Mohammadreza; Bigdeli, Mohammad Reza

doi:10.1016/j.ejphar.2016.11.011

Cited by 35 publications

(22 citation statements)

References 45 publications

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“…It provided anti‐inflammatory and antinociceptive effects not only in classical nociceptive models (Malfait et al., ; Costa et al., ), but also in models of visceral pain and multiple sclerosis (Mecha et al., ) or in patients with Parkinson's‐associated pain (Chagas et al., ) and intractable cancer pain (Johnson et al., ). The mechanisms may involve activation of nuclear receptors (O'Sullivan, ), antagonism of atypical cannabinoid receptors such as GPR55 (Johns et al., ; Ryberg et al., ), modulation of calcium fluxes via TRP channels (Campos et al., ; Iannotti et al., ), some neuroprotective effects found in models of epilepsy and cerebral ischaemia (Do Val‐da Silva et al., ; Khaksar and Bigdeli, ) and stimulation of neurogenesis (Esposito et al., ). The full spectrum and underlying mechanisms of beneficial effects of cannabidiol is still not completely understood.…”

Section: Preclinical Evidence Of Antinociceptive Effects Of Cannabinoidsmentioning

confidence: 99%

Current evidence of cannabinoid‐based analgesia obtained in preclinical and human experimental settings

Lötsch

Weyer-Menkhoff

Tegeder

2017

European Journal of Pain

109

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Section: Preclinical Evidence Of Antinociceptive Effects Of Cannabinoidsmentioning

confidence: 99%

Current evidence of cannabinoid‐based analgesia obtained in preclinical and human experimental settings

Lötsch

Weyer-Menkhoff

Tegeder

2017

European Journal of Pain

109

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“…Cannabidiol (CBD) is a non‐psychotropic natural cannabinoid typically found in cannabis plants at relatively high concentrations. Numerous studies using rodent in vivo models have shown that CBD possesses protective properties against ischemia reperfusion‐induced brain injury [5‐8]; however, the effects of CBD on HS‐induced brain injury have not been studied. A recent study using a neonatal rat model of arterial ischemic stroke reported that CBD could reduce brain damage and enhance functional recovery by inhibiting apoptosis [6]; however, the specific mechanism of this effect remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Cannabidiol alleviates hemorrhagic shock‐induced neural apoptosis in rats by inducing autophagy through activation of the PI3K/AKT pathway

Lin

Gao

et al. 2020

Fundamemntal Clinical Pharma

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Recently, several studies have reported that the pharmacological effects exerted by cannabidiol (CBD) are partially related to the regulation of autophagy. Increasing evidence indicates that autophagy provides protection against ischemia‐induced brain injury. However, the protective effect of CBD against mitochondrial‐dependent apoptosis in hemorrhagic shock (HS)‐induced brain injury has not been studied. In the present study, we observed the protective effects of CBD against neural mitochondrial‐dependent apoptosis in a rat model of HS. In addition, CBD increased Beclin‐1 and LC3II expression and reduced P62 expression, which were indicative of autophagy. CBD treatment attenuated the neural apoptosis induced by HS, as reflected by restoring mitochondrial dysfunction, downregulation of BAX, neuro‐apoptosis ratio and NF‐κB signaling activation, and upregulation of BCL2 in the cerebral cortex. Such protective effects were reversed by 3‐Methyladenine, a specific autophagy inhibitor, indicating that the protective effects of CBD treatment involved autophagy. LY294002, a PI3K inhibitor, significantly inhibited CBD‐induced autophagy, demonstrating that PI3K/AKT signaling is involved in the CBD’s regulation of autophagy. Furthermore, we found that CBD treatment upregulated PI3K/AKT signaling via cannabinoid receptor 1. Therefore, these findings suggested that CBD treatment protects against cerebral injury induced by HS‐mediated mitochondrial‐dependent apoptosis by activating the PI3K/AKT signaling pathway to reinforce autophagy.

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“…In spite of the controversy concerning the deleterious effect of CBD on OL cell cultures, some authors have identified a dose-dependent response [306,307]. Furthermore, CBD has been reported to be oligoprotective after an inflammatory damage [307], and to reduce excitotoxicity in several pathologies such as stroke or neonatal hypoxia-ischemia [58,308,309,310]. Results of our group have proved this dual effect.…”

Section: Cannabinoids and Ampa Receptormentioning

confidence: 61%

Glial Cell AMPA Receptors in Nervous System Health, Injury and Disease

Ceprián

Fulton

2019

IJMS

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Glia form a central component of the nervous system whose varied activities sustain an environment that is optimised for healthy development and neuronal function. Alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA)-type glutamate receptors (AMPAR) are a central mediator of glutamatergic excitatory synaptic transmission, yet they are also expressed in a wide range of glial cells where they influence a variety of important cellular functions. AMPAR enable glial cells to sense the activity of neighbouring axons and synapses, and as such many aspects of glial cell development and function are influenced by the activity of neural circuits. However, these AMPAR also render glia sensitive to elevations of the extracellular concentration of glutamate, which are associated with a broad range of pathological conditions. Excessive activation of AMPAR under these conditions may induce excitotoxic injury in glial cells, and trigger pathophysiological responses threatening other neural cells and amplifying ongoing disease processes. The aim of this review is to gather information on AMPAR function from across the broad diversity of glial cells, identify their contribution to pathophysiological processes, and highlight new areas of research whose progress may increase our understanding of nervous system dysfunction and disease.

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Anti-excitotoxic effects of cannabidiol are partly mediated by enhancement of NCX2 and NCX3 expression in animal model of cerebral ischemia

Cited by 35 publications

References 45 publications

Current evidence of cannabinoid‐based analgesia obtained in preclinical and human experimental settings

Current evidence of cannabinoid‐based analgesia obtained in preclinical and human experimental settings

Cannabidiol alleviates hemorrhagic shock‐induced neural apoptosis in rats by inducing autophagy through activation of the PI3K/AKT pathway

Glial Cell AMPA Receptors in Nervous System Health, Injury and Disease

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