Functions of the CB1 and CB 2 receptors in neuroprotection at the level of the blood-brain barrier.

“The cannabinoid (CB) receptors are the main targets of the cannabinoids, which include plant cannabinoids, endocannabinoids and synthetic cannabinoids. Over the last few years, accumulated evidence has suggested a role of the CB receptors in neuroprotection.

The blood-brain barrier (BBB) is an important brain structure that is essential for neuroprotection. A link between the CB receptors and the BBB is thus likely, but this possible connection has only recently gained attention.

Cannabinoids and the BBB share the same mechanisms of neuroprotection and both protect against excitotoxicity (CB1), cell death (CB1), inflammation (CB2) and oxidative stress (possibly CB independent)-all processes that also damage the BBB.

Several examples of CB-mediated protection of the BBB have been found, such as inhibition of leukocyte influx and induction of amyloid beta efflux across the BBB.

Moreover, the CB receptors were shown to improve BBB integrity, particularly by restoring the tightness of the tight junctions. This review demonstrated that both CB receptors are able to restore the BBB and neuroprotection, but much uncertainty about the underlying signaling cascades still exists and further investigation is needed.”

http://www.ncbi.nlm.nih.gov/pubmed/24929655

Cannabinoids Promote Oligodendrocyte Progenitor Survival: Involvement of Cannabinoid Receptors and Phosphatidylinositol-3 Kinase/Akt Signaling

Image result for the journal of neuroscience logo

“Cannabinoids exert pleiotropic actions in the CNS, including the inhibition of inflammatory responses and the enhancement of neuronal survival after injury… cannabinoid receptors are distributed widely in brain… Cannabinoids Promote Oligodendrocyte Progenitor Survival: Involvement of Cannabinoid Receptors and Phosphatidylinositol-3 Kinase/Akt Signaling.

Limited clinical studies have suggested that cannabis might ameliorate the symptomatology in multiple sclerosis patients, and beneficial effects of synthetic cannabinoids have been reported in vivoin rodent models of multiple sclerosis.

Apart from their actions on motor and pain pathways, cannabinoids regulate the immune response by reducing the production of inflammatory mediators by leukocytes, astrocytes, and microglia, which may contribute to their beneficial effects.

The results of the present study also point to a direct role of cannabinoids in promoting the survival of oligodendrocyte progenitors, particularly in unfavorable conditions, as would be the case in demyelinating diseases. Studies in progress are aimed to evaluate the function of cannabinoids in other models affecting oligodendroglial survival.

http://www.jneurosci.org/content/22/22/9742.long

Cannabidiol, neuroprotection and neuropsychiatric disorders.

“Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid derived from Cannabis sativa.

It has possible therapeutic effects over a broad range of neuropsychiatric disorders.

CBD attenuates brain damage associated with neurodegenerative and/or ischemic conditions.

It also has positive effects on attenuating psychotic-, anxiety- and depressive-like behaviors.

Moreover, CBD affects synaptic plasticity and facilitates neurogenesis.

The mechanisms of these effects are still not entirely clear but seem to involve multiple pharmacological targets.

In the present review, we summarized the main biochemical and molecular mechanisms that have been associated with the therapeutic effects of CBD, focusing on their relevance to brain function, neuroprotection and neuropsychiatric disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26845349

The Cannabinoid CB1/CB2 Agonist WIN55212.2 Promotes Oligodendrocyte Differentiation In Vitro and Neuroprotection During the Cuprizone-Induced Central Nervous System Demyelination.

“Different types of insults to the CNS lead to axon demyelination. Remyelination occurs when the CNS attempts to recover from myelin loss and requires the activation of oligodendrocyte precursor cells.

With the rationale that CB1 receptor is expressed in oligodendrocytes and marijuana consumption alters CNS myelination, we study the effects of the cannabinoid agonist WIN55212.2 in (1) an in vitro model of oligodendrocyte differentiation and (2) the cuprizone model for demyelination.

The cannabinoid agonist WIN55212.2 promotes oligodendrocyte differentiation in vitro.

Moreover, 0.5 mg/kg of the drug confers neuroprotection during cuprizone-induced demyelination, while 1 mg/kg aggravates the demyelination process.”

http://www.ncbi.nlm.nih.gov/pubmed/26842941

Cannabinoid receptors and their role in neuroprotection.

“Evidence has accumulated over the last few years suggesting that endocannabinoid-based drugs may potentially be useful to reduce the effects of neurodegeneration. In fact, exogenous and endogenous cannabinoids were shown to exert neuroprotection in a variety of in vitro and in vivo models of neuronal injury via different mechanisms,”

http://www.ncbi.nlm.nih.gov/pubmed/16052037

The endocannabinoid system as a target for the treatment of neuronal damage.

“Cannabinoids have been proposed as clinically promising neuroprotective molecules, based on their capability to normalize glutamate homeostasis, reducing excitotoxicity, to inhibit calcium influx, lowering intracellular levels and the subsequent activation of calcium-dependent destructive pathways, and to reduce the generation of reactive oxygen intermediates or to limit their toxicity, decreasing oxidative injury.

Cannabinoids are also able to decrease local inflammatory events by acting on glial processes that regulate neuronal survival, and to restore blood supply by reducing vasocontriction produced by several endothelium-derived factors.

Treatment of neurodegenerative disorders is a challenge for neuroscientists and neurologists. Unhappily, the efficacy of available medicines is still poor and there is an urgent need for novel neuroprotective agents. Cannabinoids can serve this purpose given their recognized antiexcitotoxic, antioxidant and anti-inflammatory properties.”

http://www.ncbi.nlm.nih.gov/pubmed/20230193

The neuroprotection of cannabidiol against MPP+-induced toxicity in PC12 cells involves trkA receptors, upregulation of axonal and synaptic proteins, neuritogenesis, and might be relevant to Parkinson’s disease.

“Cannabidiol (CBD) is a non-psychoactive constituent of Cannabis sativa with potential to treat neurodegenerative diseases.

Its neuroprotection has been mainly associated with anti-inflammatory and antioxidant events; however, other mechanisms might be involved.

We investigated the involvement of neuritogenesis, NGF receptors (trkA), NGF, and neuronal proteins in the mechanism of neuroprotection of CBD against MPP+ toxicity in PC12 cells…

This is the first study to report the involvement of neuronal proteins and trkA in the neuroprotection of CBD.

Our findings suggest that CBD has a neurorestorative potential independent of NGF that might contribute to its neuroprotection against MPP+, a neurotoxin relevant to Parkinson’s disease.”

http://www.ncbi.nlm.nih.gov/pubmed/26556726

Cannabidiol protects an in vitro model of the blood brain barrier (BBB) from oxygen-glucose deprivation via PPARγ and 5-HT1A.

“In vivo and in vitro studies have demonstrated a protective effect of cannabidiol (CBD) in reducing infarct size in stroke models, and against epithelial barrier damage in numerous disease models.

We aimed to investigate whether CBD also affects blood-brain barrier (BBB) permeability following ischaemia.

These data suggest that activity at the BBB could represent an as yet unrecognised mechanism of CBD-induced neuroprotection in ischaemic stroke, mediated by PPARγ and 5-HT1A .”

http://www.ncbi.nlm.nih.gov/pubmed/26497782

Cannabinoids produce neuroprotection by reducing intracellular calcium release from ryanodine-sensitive stores.

“Exogenously administered cannabinoids are neuroprotective in several different cellular and animal models.

In the current study, two cannabinoid CB1 receptor ligands (WIN 55,212-2, CP 55,940) markedly reduced hippocampal cell death, in a time-dependent manner, in cultured neurons subjected to high levels of NMDA…

The results suggest that cannabinoids prevent cell death by initiating a time and dose dependent inhibition of adenylyl cyclase, that outlasts direct action at the CB1 receptor and is capable of reducing [Ca2+](i) via a cAMP/PKA-dependent process during the neurotoxic event.”

http://www.ncbi.nlm.nih.gov/pubmed/15910885

Cannabinoid receptor type 1 agonist ACEA improves motor recovery and protects neurons in ischemic stroke in mice.

“Brain ischemia produces neuronal cell death and the recruitment of pro-inflammatory cells.

In turn, the search for neuroprotection against this type of insult has rendered results involving a beneficial role of endocannabinoid receptor agonists in the Central Nervous System.

In this work, to further elucidate the mechanisms associated to this neuroprotective effect…

Motor tests showed a progressive deterioration in motor activity in ischemic animals, which only ACEA treatment was able to counteract.

Our results suggest that CB1R may be involved in neuronal survival and in the regulation of neuroprotection during focal cerebral ischemia in mice.”

http://www.ncbi.nlm.nih.gov/pubmed/26296704

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