Stimulated CB1 Cannabinoid Receptor Inducing Ischemic Tolerance and Protecting Neuron from Cerebral Ischemia

Zhuang, Quankun; Dai, Cailing; Yang, Linglong; Huang, Wen; Wang, Hongyun; Jiang, Xiaoxue; Zhang, Yuyang

doi:10.2174/1871524916666160504104624

Cited by 8 publications

(7 citation statements)

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“… 25 ESC takes a significant role via several downstream signaling pathways in ischemic tolerance and protection from ischemic stroke. 53 CB1R activation is one prime underlying mechanism, it can be mediated by URB597, as has been substantiated. 54 URB597 increases CB1R-mediated neuronal survival and neurotransmission, meanwhile up-regulating the levels of BDNF expression in the brain.…”

Section: Discussionmentioning

confidence: 78%

Neuroprotective Effects of VEGF-A Nanofiber Membrane and FAAH Inhibitor URB597 Against Oxygen–Glucose Deprivation-Induced Ischemic Neuronal Injury

Wang¹,

Jin²,

Zhao

et al. 2021

IJN

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Introduction Brain ischemia is a common neurological disorder worldwide that activates a cascade of pathophysiological events involving decreases in oxygen and glucose levels. Despite substantial efforts to explore its pathogenesis, the management of ischemic neuronal injury remains an enormous challenge. Accumulating evidence suggests that VEGF modified nanofiber (NF) materials and the fatty-acid amide hydrolase (FAAH) inhibitor URB597 exert an influence on alleviating ischemic brain damage. We aimed to further investigate their effects on primary hippocampal neurons, as well as the underlying mechanisms following oxygen–glucose deprivation (OGD). Methods Different layers of VEGF-A loaded polycaprolactone (PCL) nanofibrous membranes were first synthesized by using layer-by-layer (LBL) self-assembly of electrospinning methods. The physicochemical and biological properties of VEGF-A NF membranes, and their morphology, hydrophilicity, and controlled-release of VEGF-A were then estimated. Furthermore, the effects of VEGF-A NF and URB597 on OGD-induced mitochondrial oxidative stress, inflammatory responses, neuronal apoptosis, and endocannabinoid signaling components were assessed. Results The VEGF-A NF membrane and URB597 can not only promote hippocampal neuron adhesion and viability following OGD but also exhibited antioxidant/anti-inflammatory and mitochondrial membrane potential protection. The VEGF-A NF membrane and URB597 also inhibited OGD-induced cellular apoptosis through activating CB1R signaling. These results indicate that VEGF-A could be controlled-released by LBL self-assembled NF membranes. Discussion The VEGF-A NF membrane and URB597 displayed positive synergistic neuroprotective effects through the inhibition of mitochondrial oxidative stress and activation of CB1R/PI3K/AKT/BDNF signaling, suggesting that a VEGF-A loaded NF membrane and the FAAH inhibitor URB597 could be of therapeutic value in ischemic cerebrovascular diseases.

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Section: Discussionmentioning

confidence: 78%

Neuroprotective Effects of VEGF-A Nanofiber Membrane and FAAH Inhibitor URB597 Against Oxygen–Glucose Deprivation-Induced Ischemic Neuronal Injury

Wang¹,

Jin²,

Zhao

et al. 2021

IJN

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“…Lipid peroxidation is a free-radical-mediated chain of reactions that, once initiated, results in an oxidative deterioration of polyunsaturated lipids, the components of biological membranes. There are controversial reports about the relationship between the CB1 endocannabinoid system and oxidative stress [48][49][50][51][52]. According to Mukhopadhyay et al [49], CB1 activation may amplify the reactive oxygen/nitrogen species-MAPK activation-cell death pathway by excessive inflammation and/or oxidative/nitrosative stress, which may contribute to the pathophysiology of cardiovascular diseases.…”

Section: Discussionmentioning

confidence: 99%

“…According to Mukhopadhyay et al [49], CB1 activation may amplify the reactive oxygen/nitrogen species-MAPK activation-cell death pathway by excessive inflammation and/or oxidative/nitrosative stress, which may contribute to the pathophysiology of cardiovascular diseases. Zhuang et al [52] demonstrated that CB1 is likely to provide an appropriate antioxidant balance by increasing endogenous free radical scavengers for neuroprotection.…”

Section: Discussionmentioning

confidence: 99%

In vitro assessment of the cytotoxic, genotoxic and oxidative stress effects of the synthetic cannabinoid JWH-018 in human SH-SY5Y neuronal cells

Sezer

Jannuzzi

Huestis

et al. 2020

Toxicology Research

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Background: JWH-018 was the first synthetic cannabinoid introduced as a legal high and the first of the new generation of novel psychoactive substances that flooded worldwide drug markets. JWH-018 was marketed as “spice,” “herbal incense,” or “herbal blend,” as a popular and legal (at the time) alternative to cannabis (marijuana). JWH-018 is a potent synthetic cannabinoid with considerable toxicity associated with its use. JWH-018 has qualitatively similar but quantitatively greater pharmacological effects than cannabis, leading to intoxications and even deaths. The mechanisms of action of the drug’s toxicity require research, and thus, the aim of the present study was to investigate the toxicological profile of JWH-018 in human SH-SY5Y neuronal cells. Methods: SH-SY5Y neuronal cells were exposed to increasing concentrations from 5 to 150 μM JWH-018 over 24 h. Cytotoxicity, DNA damage, the apoptotic/necrotic rate, and oxidative stress were assessed following SH-SY5Y exposure. Results: JWH-018 did not produce a significant decrease in SH-SY5Y cell viability, did not alter apoptotic/necrotic rate, and did not cause genotoxicity in SH-SY5Y cells with 24-h exposure. Glutathione reductase and catalase activities were significantly reduced; however, there was no significant change in glutathione peroxidase activity. Also, JWH-018 treatment significantly decreased glutathione concentrations, significantly increased protein carbonylation, and significantly increased malondialdehyde (MDA) concentrations. For significance, all P < 0.05. Discussion/Conclusion: JWH-018 produced oxidative stress in SH-SY5Y cells that could be an underlying mechanism of JWH-018 neurotoxicity. Additional in vivo animal and human-based studies are needed to confirm our findings.

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“…The activation of Akt can control multiple intracellular signals, such as the mTOR signaling pathway, GSK-3β signaling pathway etc. Then, the downstream signaling pathways can promote proliferation and survival after cerebral ischemia ( 48 – 50 ). In addition, some studies reported that treatment with IGF-1 after an ischemic stroke partially improved the ischemic damage of neurons induced by ischemia-reperfusion injury ( 51 , 52 ).…”

Section: Discussionmentioning

confidence: 99%

Less hippocampal neuronal death in young gerbils following transient global cerebral ischemia is associated with long‑term maintenance of insulin‑like growth factorï¿½1 and its receptors in the hippocampal CA1 region

et al. 2017

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Insulin-like growth factor 1 (IGF-1) is a well-known growth factor with well-defined neuroprotective effects against cerebral ischemia. However, the age-dependent differences in the expression of IGF-1 and its receptor (IGF-1R) in the brain following transient cerebral ischemia (TCI) have not been elucidated. In the present study, the differences in IGF-1 and IGF-1R in the gerbil hippocampal CA1 region of young and adult gerbils 5 min following TCI were determined. Seven days following TCI, the neuronal death in the hippocampal CA1 region of young gerbils was significantly less than that observed in adult gerbils. In addition, the immunoreactivity, and levels of IGF-1 and IGF-1R in the CA1 region of the normal young were higher than those in the normal adult. Four days following TCI, the immunoreactivity, and protein levels of IGF-1 and IGF-1R were markedly decreased in the adult group. By contrast, in the young group, the immunoreactivity and expression levels were much greater than those in the adult group. However, 7 days following TCI, all immunoreactivity and expression levels were markedly decreased when compared with those in the normal adult and young groups. In addition, the immunoreactivity and expression levels in the young groups were significantly higher than those of the adult groups. In conclusion, the present study demonstrated that the higher and sustained expression of IGF-1 and IGF-1R in the young gerbil hippocampal CA1 region following TCI may be associated with the reduced neuronal death compared to that in the adults.

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Stimulated CB1 Cannabinoid Receptor Inducing Ischemic Tolerance and Protecting Neuron from Cerebral Ischemia

Cited by 8 publications

References 0 publications

Neuroprotective Effects of VEGF-A Nanofiber Membrane and FAAH Inhibitor URB597 Against Oxygen–Glucose Deprivation-Induced Ischemic Neuronal Injury

Neuroprotective Effects of VEGF-A Nanofiber Membrane and FAAH Inhibitor URB597 Against Oxygen–Glucose Deprivation-Induced Ischemic Neuronal Injury

In vitro assessment of the cytotoxic, genotoxic and oxidative stress effects of the synthetic cannabinoid JWH-018 in human SH-SY5Y neuronal cells

Less hippocampal neuronal death in young gerbils following transient global cerebral ischemia is associated with long‑term maintenance of insulin‑like growth factorï¿½1 and its receptors in the hippocampal CA1 region

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