Cannabinoid receptor 2 attenuates microglial accumulation and brain injury following germinal matrix hemorrhage via ERK dephosphorylation in vivo and in vitro.

Posted on May 13, 2015 by David

“Microglia accumulation plays detrimental roles in the pathology of germinal matrix hemorrhage (GMH) in the immature preterm brain.

Here, we investigated the effects of a cannabinoid receptor 2 (CB2R) agonist on microglia proliferation and the possible involvement of the mitogen-activated protein kinase (MAPK) family pathway in a collagenase-induced GMH rat model and in thrombin-induced rat microglia cells.

Overall, these findings suggest that activation of the endocannabinoid system might attenuate inflammation-induced secondary brain injury after GMH in rats by reducing microglia accumulation through a mechanism involving ERK dephosphorylation.

Enhancing CB2R activation is a potential treatment to slow down the course of GMH in preterm newborns.”

http://www.ncbi.nlm.nih.gov/pubmed/25963415

http://www.thctotalhealthcare.com/category/brain-trauma/

A Basal Tone of 2-Arachidonoylglycerol Contributes to Early Oligodendrocyte Progenitor Proliferation by Activating Phosphatidylinositol 3-Kinase (PI3K)/AKT and the Mammalian Target of Rapamycin (MTOR) Pathways.

Posted on April 23, 2015 by David

“A basal tone of the endocannabinoid 2-arachidonoylglycerol (2-AG) enhances late oligodendrocyte progenitor cell (OPC) differentiation. Here, we investigated whether endogenous 2-AG may also promote OPC proliferation in earlier stages…

Our data suggest that proliferation of early OPCs stimulated by PDGF-AA and bFGF depends on the tonic activation of cannabinoid receptors by endogenous 2-AG and provide further evidence on the role of endocannabinoids in oligodendrocyte development, being important for the maintenance and self-renewal of the OPCs.

The results highlight the therapeutic potential of the endocannabinoid signaling in the emerging field of brain repair.”

http://www.ncbi.nlm.nih.gov/pubmed/25900077

The interactive role of cannabinoid and vanilloid systems in hippocampal synaptic plasticity in rats.

Posted on April 7, 2015 by David

“Long-term potentiation (LTP) has been most thoroughly studied in the hippocampus, which has a key role in learning and memory. Endocannabinoids are one of the endogenous systems that modulate this kind of synaptic plasticity. The activation of the vanillioid system has also been shown to mediate synaptic plasticity in the hippocampus. In addition, immunohistochemical studies have shown that cannabinoid receptor type 1 (CB1) and vanilloid receptor 1 (TRPV1) are closely located in the hippocampus.

It seems that agonists of the vanilloid system modulate cannabinoid outputs that cause an increase in synaptic plastisity, while in contemporary consumption of two agonist, TRPV1 agonist can change production of endocannabinoid, which in turn result to enhancement of LTP induction. These findings suggest that the two systems may interact or share certain common signaling pathways in the hippocampus.”

http://www.ncbi.nlm.nih.gov/pubmed/25843413

Palmitoyl Serine: An Endogenous Neuroprotective Endocannabinoid-Like Entity After Traumatic Brain Injury.

Posted on April 2, 2015 by David

“The endocannabinoid (eCB) system helps recovery following traumatic brain injury (TBI).

Treatment with 2-arachidonoylglycerol (2-AG), a cerebral eCB ligand, was found to ameliorate the secondary damage.

Interestingly, the fatty acid amino acid amide (FAAA) N-arachidonoyl-L-serine (AraS) exerts similar eCB dependent neuroprotective. The present study aimed to investigate the effects of the FAAA palmitoyl-serine (PalmS) following TBI.

We suggest that the neuroprotective action of PalmS is mediated by indirect activation of the eCB receptors following TBI. One such mechanism may involve receptor palmitoylation which has been reported to result in structural stabilization of the receptors and to an increase in their activity. Further research is required in order to establish this assumption.”

http://www.ncbi.nlm.nih.gov/pubmed/25721934

http://www.thctotalhealthcare.com/category/brain-trauma/

Cannabinoid agonist rescues learning and memory after a traumatic brain injury.

Posted on March 31, 2015 by David

“Traumatic brain injury (TBI) can cause persistent challenges including problems with learning and memory.

Previous studies suggest that the activation of the cannabinoid 1 receptor after a traumatic brain injury could be beneficial.

We tested the hypothesis that posttraumatic brain injury administration of a cannabinoid 1 receptor agonist can rescue deficits in learning and memory.

Young adult male rats were subjected to a moderately severe controlled cortical impact brain injury, with a subset given postinjury i.p. injections of a cannabinoid receptor agonist.

Utilizing novel object recognition and the morris water task, we found that the brain-injured animals treated with the agonist showed a marked recovery.”

http://www.ncbi.nlm.nih.gov/pubmed/25815355

“Taken together, this study shows that the administration of a CB1R agonist after a TBI rescues deficits in learning and memory.” http://onlinelibrary.wiley.com/doi/10.1002/acn3.163/full

http://www.thctotalhealthcare.com/category/brain-trauma/

Molecular Mechanisms of Cannabinoid Protection from Neuronal Excitotoxicity

Posted on February 25, 2015 by David

“Cannabinoids protect neurons from excitotoxic injury…

Endogenous or exogenous cannabinoids have shown neuroprotective effects…

The main finding reported here is that cannabinoids protect neurons from excitotoxic injury by a mechanism that involves the activation of CB1R and inhibition of NOS and PKA….

Cannabinoid receptor agonist drugs protect neurons…

By identifying the signaling pathways responsible for cannabinoid effects in animal models of disease and their human counterparts, it may be possible to design more specific and therefore more efficacious cannabinoid-based therapies.”

http://molpharm.aspetjournals.org/content/69/3/691.long

“Delta9-tetrahydrocannabinol protects hippocampal neurons from excitotoxicity.” http://www.ncbi.nlm.nih.gov/pubmed/17140550

Effect of Marijuana Use on Outcomes in Traumatic Brain Injury.

Posted on September 30, 2014 by David

“Traumatic brain injury (TBI) is associated with significant morbidity (sickness) and mortality (death).

Several studies have demonstrated neuroprotective effects of cannabinoids.

The objective of this study was to establish a relationship between the presence of a positive toxicology screen for tetrahydrocannabinol (THC) and mortality after TBI…

After adjusting for differences between the study cohorts on logistic regression, a THC(+) screen was independently associated with survival after TBI.

A positive THC screen is associated with decreased mortality in adult patients sustaining TBI.”

http://www.ncbi.nlm.nih.gov/pubmed/25264643

http://www.thctotalhealthcare.com/category/brain-trauma/

Using the endocannabinoid system as a neuroprotective strategy in perinatal hypoxic-ischemic brain injury.

Posted on September 12, 2014 by David

“One of the most important causes of brain injury in the neonatal period is a perinatal hypoxic-ischemic event. This devastating condition can lead to long-term neurological deficits or even death. After hypoxic-ischemic brain injury, a variety of specific cellular mechanisms are set in motion, triggering cell damage and finally producing cell death.

Effective therapeutic treatments against this phenomenon are still unavailable because of complex molecular mechanisms underlying hypoxic-ischemic brain injury. After a thorough understanding of the mechanism underlying neural plasticity following hypoxic-ischemic brain injury, various neuroprotective therapies have been developed for alleviating brain injury and improving long-term outcomes.

Among them, the endocannabinoid system emerges as a natural system of neuroprotection.

The endocannabinoid system modulates a wide range of physiological processes in mammals and has demonstrated neuroprotective effects in different paradigms of acute brain injury, acting as a natural neuroprotectant.

The aim of this review is to study the use of different therapies to induce long-term therapeutic effects after hypoxic-ischemic brain injury, and analyze the important role of the endocannabinoid system as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury.”

http://www.ncbi.nlm.nih.gov/pubmed/25206720

Mechanisms of control of neuron survival by the endocannabinoid system.

Posted on July 6, 2014 by David

“Endocannabinoids act as retrograde messengers that, by inhibiting neurotransmitter release via presynaptic CB(1) cannabinoid receptors, regulate the functionality of many synapses. In addition, the endocannabinoid system participates in the control of neuron survival.

Thus, CB(1) receptor activation has been shown to protect neurons from acute brain injury as well as in neuroinflammatory conditions and neurodegenerative diseases.

Cannabinoid neuroprotective activity relies on the inhibition of glutamatergic neurotransmission and on other various mechanisms, and is supported by the observation that the brain overproduces endocannabinoids upon damage.

Besides promoting neuroprotection, a role for the endocannabinoid system in the control of neurogenesis from neural progenitors has been put forward. In addition, activation of CB(2) cannabinoid receptors on glial cells may also participate in neuroprotection by limiting the extent of neuroinflammation.

Altogether, these findings support that endocannabinoids constitute a new family of lipid mediators that act as instructive signals in the control of neuron survival.”

http://www.ncbi.nlm.nih.gov/pubmed/18781978

Defective Adult Neurogenesis in CB1 Cannabinoid Receptor Knockout Mice

Posted on July 5, 2014 by David

Fig. 1.

“…endogenous cannabinoid signaling mechanisms may represent a key component of cell-survival programs mobilized in the injured brain.

In addition to their neuroprotective effects, cannabinergic systems may also have an important role in brain development…

…expression of endocannabinoids and cannabinoid receptors in brain…

Neurogenesis, or the birth of new neurons, continues to occur beyond development and into adulthood, and several lines of evidence suggest that cannabinoid signaling may be involved in this process as well…

In addition to the well known effects of growth factors, a variety of drugs has been shown to influence adult neurogenesis. These include excitatory amino acid receptor antagonists, antidepressants, lithium, nitric oxide donors, phosphodiesterase inhibitors, and statins.

Together with the finding that neurogenesis can be regulated by cannabinoids, these observations imply that a broad range of pharmacological approaches may exist through which to modify neurogenesis for therapeutic purposes.”

http://molpharm.aspetjournals.org/content/66/2/204.full