“Targeting the CB2 receptor afforded neuroprotection in SOD1G93A mutant mice, a model of amyotrophic lateral sclerosis (ALS). The neuroprotective effects of CB2 receptors were facilitated by their up-regulation in the spinal cord in SOD1G93A mutant mice. Herein, we have investigated whether a similar CB2 receptor up-regulation, as well as parallel changes in other endocannabinoid elements, are evident in the spinal cord of dogs with degenerative myelopathy (DM), caused from mutations in the superoxide dismutase 1 gene (SOD1). In summary, our results demonstrated a marked up-regulation of CB2 receptors occurring in the spinal cord in canine DM, which was concentrated in activated astrocytes. Such receptors may be used as a potential target to enhance the neuroprotective effects exerted by these glial cells.” https://www.ncbi.nlm.nih.gov/pubmed/28069688]]>
Tag Archives: neuroprotection
Potential roles of (endo)cannabinoids in the treatment of glaucoma: from intraocular pressure control to neuroprotection.
“Recent evidence shows that the endocannabinoid system is involved in the pathogenesis of numerous neurodegenerative diseases of the central nervous system. Pharmacologic modulation of cannabinoid receptors or the enzymes involved in the synthesis, transport, or breakdown of endogenous cannabinoids has proved to be a valid alternative to conventional treatment of these diseases.
In this review, we will examine recent findings that demonstrate the involvement of the endocannabinoid system in glaucoma, a major neurodegenerative disease of the eye that is a frequent cause of blindness.
Experimental findings indicate that the endocannabinoid system contributes to the control of intraocular pressure (IOP), by modulating both production and drainage of aqueous humor.
There is also a growing body of evidence of the involvement of this system in mechanisms leading to the death of retinal ganglion cells, which is the end result of glaucoma.
Molecules capable of interfering with the ocular endocannabinoid system could offer valid alternatives to the treatment of this disease, based not only on the reduction of IOP but also on neuroprotection.”
https://www.ncbi.nlm.nih.gov/pubmed/18929127
[Possibilities of applying cannabinoids' in the treatment of glaucoma].
“Over a period of several decades numerous scientific research has proven that, regardless of the route of administration, cannabinoids are able to decrease intraocular pressure. What is more, these compounds are characterized by neuroprotection and vasodilatation properties, that additionally substantiate it’s therapeutic utility in conservative treatment of glaucoma. So far, it has not been described in details what mechanism is used to lower the intraocular pressure by cannabinoids. Nevertheless, the presence of endocannabinoid receptors in structures of the eye responsible for formation and outflow of aqueous humor is an explanation for effectiveness of these compounds, when administered in topical form. These days, with the aid of modern pharmacological technology are available significantly bigger possibilities of improving bioavailability of cannabinoids administered to the eye than in the past, as well as limitation of it’s undesired side effects.” https://www.ncbi.nlm.nih.gov/pubmed/19112869]]>
[Possibilities of applying cannabinoids’ in the treatment of glaucoma].
“Over a period of several decades numerous scientific research has proven that, regardless of the route of administration, cannabinoids are able to decrease intraocular pressure.
What is more, these compounds are characterized by neuroprotection and vasodilatation properties, that additionally substantiate it’s therapeutic utility in conservative treatment of glaucoma.
So far, it has not been described in details what mechanism is used to lower the intraocular pressure by cannabinoids. Nevertheless, the presence of endocannabinoid receptors in structures of the eye responsible for formation and outflow of aqueous humor is an explanation for effectiveness of these compounds, when administered in topical form.
These days, with the aid of modern pharmacological technology are available significantly bigger possibilities of improving bioavailability of cannabinoids administered to the eye than in the past, as well as limitation of it’s undesired side effects.”
The arguments for and against cannabinoids application in glaucomatous retinopathy.
“Glaucoma represents several optic neuropathies leading to irreversible blindness through progressive retinal ganglion cell (RGC) loss. Reduction of intraocular pressure (IOP) is known as the only modifiable factor in the treatment of this disorder.
Application of exogenous cannabinoids to lower IOP has attracted attention of scientists as potential agents for the treatment of glaucoma.
Accordingly, neuroprotective effect of these agents has been recently described through modulation of endocannabinoid system in the eye.
In the present work, pertinent information regarding ocular endocannabinoid system, mechanism of exogenous cannabinoids interaction with the ocular endocannabinoid system to reduce IOP, and neuroprotection property of cannabinoids will be discussed according to current scientific literature.
In addition to experimental studies, bioavailability of cannabinoids, clinical surveys, and adverse effects of application of cannabinoids in glaucoma will be reviewed.”
Cannabidiol reduces brain damage and improves functional recovery in a neonatal rat model of arterial ischemic stroke.
“Currently there is no effective treatment for neonatal arterial ischemic stroke (AIS).
Cannabidiol (CBD) is neuroprotective in models of newborn hypoxic-ischemic brain damage and adult stroke.
The purpose of this work was to study the protective effect of CBD in a neonatal rat model of AIS.
RESULTS:
CBD administration improved neurobehavioral function regarding strength, hemiparesis, coordination and sensorimotor performance as assessed at P15 and P38. MRI indicated that CBD did not reduce the volume of infarct but reduced the volume of perilesional gliosis. H+-MRS indicated that CBD reduced metabolic derangement and excitotoxicty, and protected astrocyte function. Histologic studies indicated that CBD reduced neuronal loss and apoptosis, and modulated astrogliosis and microglial proliferation and activation.
CONCLUSIONS:
CBD administration after Middle Cerebral Artery Occlusion (MCAO) led to long-term functional recovery, reducing neuronal loss and astrogliosis, and modulating apoptosis, metabolic derangement, excitotoxicity and neuro-inflammation.”
https://www.ncbi.nlm.nih.gov/pubmed/28012949
“Post-stroke administration of Cannabidiol (CBD) is neuroprotective in neonatal rats. CBD neuroprotection is sustained in the long term. CBD treatment led to functional recovery in both motor and sensorimotor domains. CBD modulated excitotoxicity, astrocyte dysfunction and microglial activation.”
https://www.sciencedirect.com/science/article/pii/S0028390816305810
Cannabinoid receptors and TRPA1 on neuroprotection in a model of retinal ischemia.
“Retinal ischemia is a pathological event present in several retinopathies such as diabetic retinopathy and glaucoma, leading to partial or full blindness with no effective treatment available.
Since synthetic and endogenous cannabinoids have been studied as modulators of ischemic events in the central nervous system (CNS), the present study aimed to investigate the involvement of cannabinoid system in the cell death induced by ischemia in an avascular (chick) retina.
We observed that chick retinal treatment with a combination of WIN 55212-2 and cannabinoid receptor antagonists (either AM251/O-2050 or AM630) decreased the release of lactate dehydrogenase (LDH) induced by retinal ischemia in an oxygen and glucose deprivation (OGD) model.
Further, the increased availability of endocannabinoids together with cannabinoid receptor antagonists also had a neuroprotective effect.
Surprisingly, retinal exposure to any of these drugs alone did not prevent the release of LDH stimulated by OGD.
Since cannabinoids may also activate transient receptor potential (TRP) channels, we investigated the involvement of TRPA1 receptors (TRPA1) in retinal cell death induced by ischemic events.
We demonstrated the presence of TRPA1 in the chick retina, and observed an increase in TRPA1 content after OGD, both by western blot and immunohistochemistry.
In addition, the selective activation of TRPA1 by mustard oil (MO) did not worsen retinal LDH release induced by OGD, whereas the blockage of TRPA1 completely prevented the extravasation of cellular LDH in ischemic condition.
Hence, these results show that during the ischemic event there is an augment of TRPA1, and activation of this receptor is important in cell death induction.
The data also indicate that metabotropic cannabinoid receptors, both type 1 and 2, are not involved with the cell death found in the early stages of ischemia. Therefore, the study points to a potential role of TRPA1 as a target for neuroprotective approaches in retinal ischemia.”
Cannabinoids prevent the amyloid β-induced activation of astroglial hemichannels: A neuroprotective mechanism.
“The mechanisms involved in Alzheimer’s disease are not completely understood and how astrocytes and their gliotransmission contribute to this neurodegenerative disease remains to be fully elucidated.
Previous studies have shown that amyloid-β peptide (Aβ) induces neuronal death by a mechanism that involves the excitotoxic release of ATP and glutamate associated to astroglial hemichannel opening.
We have demonstrated that synthetic and endogenous cannabinoids (CBs) reduce the opening of astrocyte Cx43 hemichannels evoked by activated microglia or inflammatory mediators.
Nevertheless, whether CBs could prevent the astroglial hemichannel-dependent death of neurons evoked by Aβ is unknown.
We report that CBs fully prevented the hemichannel activity and inflammatory profile evoked by Aβ in astrocytes.
Moreover, CBs fully abolished the Aβ-induced release of excitotoxic glutamate and ATP associated to astrocyte Cx43 hemichannel activity, as well as neuronal damage in hippocampal slices exposed to Aβ.
Consequently, this work opens novel avenues for alternative treatments that target astrocytes to maintain neuronal function and survival during AD.”
Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke.
“Cannabis contains the psychoactive component delta⁸-tetrahydrocannabinol (delta⁸-THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and cannabigerol.
It is well-known that delta⁸-THC and other cannabinoid CB₁ receptor agonists are neuroprotective during global and focal ischemic injury.
Additionally, delta⁸-THC also mediates psychological effects through the activation of the CB₁ receptor in the central nervous system.
In addition to the CB₁ receptor agonists, cannabis also contains therapeutically active components which are CB₁ receptor independent.
Of the CB₁ receptor-independent cannabis, the most important is CBD.
In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD.
In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson’s disease, Alzheimer’s disease, and rheumatoid arthritis.
The cerebroprotective action of CBD is CB₁ receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance.
In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke.”
Neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol in hypoxic-ischemic newborn piglets.
“To test the neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol (CBD), piglets received i.v. CBD or vehicle after hypoxia-ischemia (HI: temporary occlusion of both carotid arteries plus hypoxia).
CBD administration was free from side effects; moreover, CBD administration was associated with cardiac, hemodynamic, and ventilatory beneficial effects.
In conclusion, administration of CBD after HI reduced short-term brain damage and was associated with extracerebral benefits.”