Tag Archives: neuroprotection

Time-Dependent Protection of CB2 Receptor Agonist in Stroke.

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“Recent studies have indicated that type 2 cannabinoid receptor (CB2R) agonists reduce neurodegeneration after brain injury through anti-inflammatory activity.

The purpose of this study was to examine the time-dependent interaction of CB2R and inflammation in stroke brain.

In conclusion, our data support a time-dependent neuroprotection of CB2 agonist in an animal model of stroke.

Delayed post- treatment with PPAR-γ agonist induced behavioral recovery and microglial suppression; early treatment with CB2R agonist suppressed neurodegeneration in stroke animals.”

http://www.ncbi.nlm.nih.gov/pubmed/26186541

http://www.thctotalhealthcare.com/category/stroke-2/

CB2 receptor agonists protect human dopaminergic neurons against damage from HIV-1 gp120.

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“The global pandemic of HIV infection currently afflicts 34 million individuals, has killed over 25 million people since 1981, and is the cause of death in an estimated 1.8 million people per year.

Despite the therapeutic impact of anti-retroviral therapy, HIV-1-associated neurocognitive disorder (HAND) remains a serious threat to AIDS patients…

Synthetic cannabinoids inhibit HIV-1 expression in human microglia, suppress production of inflammatory mediators in human astrocytes, and there is substantial literature demonstrating the neuroprotective properties of cannabinoids in other neuropathogenic processes.

Based on these data, experiments were designed to test the hypothesis that synthetic cannabinoids will protect dopaminergic neurons against the toxic effects of the HIV-1 protein gp120. Using a human mesencephalic neuronal/glial culture model…

These data suggest that synthetic cannabinoids are capable of protecting human dopaminergic neurons from gp120 in a variety of ways, acting principally through the CB2 receptors and microglia.

Overall, this study confirms that gp120 is capable of damaging human dopaminergic neurons, that this damage involves human microglia, and that synthetic cannabinoids can alleviate this damage through mechanisms involving human microglia.

Thus, the results of these experiments set the stage for further studies designed to tease out the role human microglia have in the mechanisms underlying the toxic effects of HIV-1 on human dopaminergic neurons and understanding the microglial-centered mechanisms underlying the protective effects of selected synthetic cannabinoids.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798286/

Ultralow doses of cannabinoid drugs protect the mouse brain from inflammation-induced cognitive damage.

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“In our previous studies, we found that a single ultralow dose of tetrahydrocannabinol (THC)… protects the brain from different insults that cause cognitive deficits.

Because various insults may trigger a neuroinflammatory response that leads to secondary damage to the brain, the current study tested whether this extremely low dose of THC could protect the brain from inflammation-induced cognitive deficits…

Our results suggest that an ultralow dose of THC that lacks any psychotrophic activity protects the brain from neuroinflammation-induced cognitive damage and might be used as an effective drug for the treatment of neuroinflammatory conditions, including neurodegenerative diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/25042014

Combined neuroprotective action of adenosine A1 and cannabinoid CB1 receptors against NMDA-induced excitotoxicity in the hippocampus.

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“Both adenosine A1 and cannabinoid CB1 receptors trigger similar transduction pathways and protect against neurotoxic insults at the hippocampus, but their combined neuroprotective potential has not been investigated.

We set forth to assess the combined action of A1 and CB1 receptors against glutamate NMDA receptor-mediated excitotoxicity at the hippocampus…

The results suggest that both CB1 and A1 receptors produce additive cumulative neuroprotection against NMDA-induced excitotoxicity in the hippocampus.”

http://www.ncbi.nlm.nih.gov/pubmed/26065937

New horizons for newborn brain protection: enhancing endogenous neuroprotection.

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“Intrapartum-related events are the third leading cause of childhood mortality worldwide and result in one million neurodisabled survivors each year. Infants exposed to a perinatal insult typically present with neonatal encephalopathy (NE).

The contribution of pure hypoxia-ischaemia (HI) to NE has been debated; over the last decade, the sensitising effect of inflammation in the aetiology of NE and neurodisability is recognised.

Therapeutic hypothermia is standard care for NE in high-income countries; however, its benefit in encephalopathic babies with sepsis or in those born following chorioamnionitis is unclear.

It is now recognised that the phases of brain injury extend into a tertiary phase, which lasts for weeks to years after the initial insult and opens up new possibilities for therapy.

There has been a recent focus on understanding endogenous neuroprotection and how to boost it or to supplement its effectors therapeutically once damage to the brain has occurred as in NE.

In this review, we focus on strategies that can augment the body’s own endogenous neuroprotection.

We discuss in particular remote ischaemic postconditioning whereby endogenous brain tolerance can be activated through hypoxia/reperfusion stimuli started immediately after the index hypoxic-ischaemic insult.

Therapeutic hypothermia, melatonin, erythropoietin and cannabinoids are examples of ways we can supplement the endogenous response to HI to obtain its full neuroprotective potential.

Achieving the correct balance of interventions at the correct time in relation to the nature and stage of injury will be a significant challenge in the next decade.”

http://www.ncbi.nlm.nih.gov/pubmed/26063194

Promising cannabinoid-based therapies for Parkinson’s disease: motor symptoms to neuroprotection.

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“Parkinson’s disease (PD) is a slow insidious neurological disorder characterized by a loss of dopaminergic neurons in the midbrain. Although several recent preclinical advances have proposed to treat PD, there is hardly any clinically proved new therapeutic for its cure.

Increasing evidence suggests a prominent modulatory function of the cannabinoid signaling system in the basal ganglia. Hence, use of cannabinoids as a new therapeutic target has been recommended as a promising therapy for PD.

The elements of the endocannabinoid system are highly expressed in the neural circuit of basal ganglia wherein they bidirectionally interact with dopaminergic, glutamatergic, and GABAergic signaling systems.

As the cannabinoid signaling system undergoes a biphasic pattern of change during progression of PD, it explains the motor inhibition typically observed in patients with PD.

Cannabinoid agonists such as WIN-55,212-2 have been demonstrated experimentally as neuroprotective agents in PD, with respect to their ability to suppress excitotoxicity, glial activation, and oxidative injury that causes degeneration of dopaminergic neurons.

Additional benefits provided by cannabinoid related compounds including CE-178253, oleoylethanolamide, nabilone and HU-210 have been reported to possess efficacy against bradykinesia and levodopa-induced dyskinesia in PD.

Despite promising preclinical studies for PD, use of cannabinoids has not been studied extensively at the clinical level. In this review, we reassess the existing evidence suggesting involvement of the endocannabinoid system in the cause, symptomatology, and treatment of PD. We will try to identify future threads of research that will help in the understanding of the potential therapeutic benefits of the cannabinoid system for treating PD.”

http://www.ncbi.nlm.nih.gov/pubmed/25888232

“To conclude, development of safe, effective cannabis-based medicines targeting different mechanisms may have a significant impact in PD therapy.”

Full-text: http://www.molecularneurodegeneration.com/content/10/1/17

http://www.thctotalhealthcare.com/category/parkinsons-disease/

Involvement of GluR2 up-regulation in neuroprotection by electroacupuncture pretreatment via cannabinoid CB1 receptor in mice.

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“We investigated whether glutamate receptor subunit 2 (GluR2) is involved in EA pretreatment-induced neuroprotection via cannabinoid CB1 receptors (CB1R) after global cerebral ischemia in mice…

In conclusion, GluR2 up-regulation is involved in neuroprotection of EA pretreatment against GCI through CB1R, suggesting that GluR2 may be a novel target for stroke intervention.”

http://www.ncbi.nlm.nih.gov/pubmed/25830356

http://www.thctotalhealthcare.com/category/stroke-2/

Neuroprotective Effect of(−)Δ9-Tetrahydrocannabinol and Cannabidiol in N-Methyl-d-Aspartate-Induced Retinal Neurotoxicity

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“In glaucoma, the increased release of glutamate is the major cause of retinal ganglion cell death. Cannabinoids have been demonstrated to protect neuron cultures from glutamate-induced death.

In this study, we test the hypothesis that glutamate causes apoptosis of retinal neurons via the excessive formation of peroxynitrite, and that the neuroprotective effect of the psychotropic Δ9-tetrahydroxycannabinol (THC) or nonpsychotropic cannabidiol (CBD) is via the attenuation of this formation…

The neuroprotection by THC and CBD was because of attenuation of peroxynitrite.

The effect of THC was in part mediated by the cannabinoid receptor CB1.

These results suggest the potential use of CBD as a novel topical therapy for the treatment of glaucoma.

THC and CBD, are similarly potent antioxidants that protect neuron cultures from glutamate-induced cell death or oxidative stress…

In addition to possessing neuroprotective or retinal neuroprotective activity… cannabinoids, such as THC, have been demonstrated to induce dose-related reductions in intraocular pressure in human and in animal models. 

This suggests that cannabinoids may offer a multifaceted therapy for glaucoma.

In conclusion, our results indicate that lipid peroxidation and ONOO− formation play an important role in NMDA-induced retinal neurotoxicity and cell loss in the retina, and that THC and CBD, by reducing the formation of these compounds, are effective neuroprotectants.

The present studies could form the basis for the development of new topical therapies for the treatment of glaucoma.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892413/

http://www.thctotalhealthcare.com/category/glaucoma-2/

The CB1 cannabinoid receptor signals striatal neuroprotection via a PI3K/Akt/mTORC1/BDNF pathway.

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“The CB1 cannabinoid receptor, the main molecular target of endocannabinoids and cannabis active components, is the most abundant G protein-coupled receptor in the mammalian brain.

In particular, the CB1 receptor is highly expressed in the basal ganglia, mostly on terminals of medium-sized spiny neurons, where it plays a key neuromodulatory function.

The CB1 receptor also confers neuroprotection in various experimental models of striatal damage…

Here, by using an array of pharmacological, genetic and pharmacogenetic approaches, we show that (1) CB1receptor engagement protects striatal cells from excitotoxic death via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin complex 1 pathway, which, in turn, (2) induces brain-derived neurotrophic factor (BDNF) expression through the selective activation of BDNF gene promoter IV, an effect that is mediated by multiple transcription factors.

Collectively, these findings unravel a molecular link between CB1 receptor activation and BDNF expression, and support the relevance of the CB1/BDNF axis in promoting striatal neuron survival.”

http://www.ncbi.nlm.nih.gov/pubmed/25698444

Cannabidiol increases survival and promotes rescue of cognitive function in a murine model of Cerebral Malaria.

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Neuroscience

“Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparuminfection that might cause permanent neurological deficits.

Cannabidiol (CBD) is a nonpsychotomimetic compound of Cannabis sativa with neuroprotective properties.

In the present work, we evaluated the effects of CBD in a murine model of CM.

CBD treatment resulted in an increase in BDNF expression in the hippocampus and decreased levels of proinflammatory cytokines in the hippocampus (TNF-α) and prefrontal cortex (IL-6).

Our results indicate that CBD exhibits neuroprotective effects in CM model and might be useful as an adjunctive therapy to prevent neurological symptoms following this disease.”

http://www.ncbi.nlm.nih.gov/pubmed/25595981

“Cannabidiol adjuvant treatment increases survival in the murine model of CM. Cannabidiol adjuvant treatment promotes rescue of behavioral and cognitive function.”

https://www.sciencedirect.com/science/article/pii/S0306452215000196

http://www.thctotalhealthcare.com/category/malaria/