The Cannabinoid WIN55212-2 Promotes Neural Repair After Neonatal Hypoxia–Ischemia

Figure 1.

“In the last years, cannabinoids have emerged as promising neuroprotective agents in several animal paradigms of acute and degenerative brain damage. Most neuroprotective effects of cannabinoids result from the activation of cannabinoid Type 1 (CB1R) and Type 2 (CB2R) receptors in neural and immune cells.

Besides, the stimulating effect of cannabinoids on proliferation, survival, and differentiation of neural progenitor cells provides interesting prospects for long-term neural repair after acute brain damage.

The endocannabinoid system has been involved in the modulation of neural stem cells proliferation, survival and differentiation as well as in the generation of new oligodendrocyte progenitors in the postnatal brain. The present work aims to test the effect of the synthetic Type 1 and Type 2 cannabinoid receptor agonist WIN55212-2 on these processes in the context of neonatal rat brain hypoxia–ischemia (HI)…

Our results suggest that the activation of the endocannabinoid system promotes white and gray matter recovery after neonatal HI injury…

In conclusion, we have demonstrated that the synthetic cannabinoid WIN55212-2 enhances SVZ cell proliferation, oligodendrogenesis, white matter remyelination, and neuroblast generation after neonatal HI.

These findings, summed to the previously described neuroprotective properties of cannabinoids after acute brain damage, may possess therapeutic repercussions in the long-term management of neonatal HI encephalopathy, a prevalent and devastating condition for which no pharmacological treatments are yet available.”

http://stroke.ahajournals.org/content/41/12/2956.full

 

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Activation of cannabinoid 2 receptors protects against cerebral ischemia by inhibiting neutrophil recruitment

Figure 1.

“THE CONSEQUENCES OF ISCHEMIC INJURY in liver, heart, and brain can be ameliorated by cannabinoids, a group of diverse compounds that include constituents of the plant Cannabis sativa (phytocannabinoids), endogenous lipids (endocannabinoids), and synthetic substances. Most of the effects of cannabinoids are mediated by the G-protein-coupled receptors cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2)… 

Cannabinoids protect against ischemic stroke…

Activation of the cannabinoid 2 receptor (CB2) reduces ischemic injury in several organs…

In conclusion, our data demonstrate that by activating p38 in neutrophils, CB2 agonists inhibit neutrophil recruitment to the brain and protect against ischemic brain injury.”

http://www.fasebj.org/content/24/3/788.long

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Researchers Meet to Discuss Cannabinoid-Based Stroke Therapy

Murikinati et al., 2010 shows that brain tissue is saved after a stroke with JWH-133

“The Cannabinoid Discussion Group at Temple University met for the second time this semester to review a recent scientific publication from a German Laboratory. The presenter was Zachary Reichenbach, an MD/Ph.D student at Temple, who is currently working in the laboratory of Dr.Ron Tuma. The Tuma lab is focused on studying cannabinoid based therapies for the treatment of cerebral ischemia resulting from stroke. Mr.Reichenbach led the discussion on a research paper which showed that the cannabinoid JWH-133 activates the cannabinoid type 2 receptor (CB2R), resulting a decrease in infarct size or brain damage duringreperfusion following an ischemic event.

Mr.Reichenbach provided background on stroke, stating that it is the 3rd cause of death in this country, and 85% of those strokes are of the ischemic variety. During an ischemic event there is a hyper-immune response resulting in the recruitment of immune cells that kill brain tissue. Cannabinoids have been shown to modulate the immune system, notably the Tuma lab has published data on the CB2 receptor’s anti-inflammatory effects. Activating the CB2 receptor decreases the migration of hyper-immune cells to the brain. The more brain you save, the more you save someone from disabilities or death.

When asked about the implications of these findings on a cannabinoid that could be a potential stroke therapy, Mr.Reichenbach replied that the results of his work and others is promising…

And just in case you were wondering, THC, the active ingredient in Cannabis, activates both the CB1 and CB2 receptor.”

http://www.examiner.com/article/researchers-meet-to-discuss-cannabinoid-based-stroke-therapy

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Cannabis gives stroke patients hope

“New research by University of Otago scientists suggests some mechanisms in the brain targeted by cannabis could become drugs targets to counter brain cell damage after a stroke.

Researchers from the Medical School’s Department of Pharmacology and Toxicology have been the first in the world to show the cannabinoid CB2 receptor appears in the rat brain following a stroke. Their findings were published recently in the journal Neuroscience Letters.

Dr John Ashton says the CB2 receptor is a protein produced as part of the body’s immune response system.

“This response is triggered by stroke and causes the inflammation that leads to damage in the area of the brain around where the stroke has occurred.

“If the inflammation can be stopped or reduced then it offers the hope of reducing the extent of the damage caused by stroke – and CB2 offers a potential target for such a drug.”"

http://www.sciencealert.com.au/news/20071404-15007.html

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Cannabinoids and Neuroprotection in Stroke

“One of the most recently described neural signaling systems is that mediated by endogenous cannabinoids (endocannabinoids). Cannabinoids have recently been shown to attenuate neuronal injury induced by hypoxia and glucose deprivation in cell culture, as well as injury induced in rat brain following both global and focal cerebral ischemia in vivo.

Two endocannabinoids have been characterized in detail: N-arachidonylethanolamide and 2-arachidonylglycerol. Cannabinoid CB1 and CB2receptors have been cloned and an alternatively spliced CB1A isoform has been identified.

The development of metabolically stable, synthetic, enantiomeric cannabinoid receptor agonists and of CB1 and CB2 receptor antagonists has greatly aided the characterization of cannabinoid receptor-mediated processes, although certain aspects of cannabinoid signaling in some systems remain poorly understood.

Indirect evidence suggests that cannabinoids might serve as endogenous regulators of ischemic neuronal injury, but several recent reports provide more direct evidence bearing on such a role.

The author’s own findings provide evidence for CB1 receptor-mediated neuroprotection in vivo, but non-receptor-mediated protection in vitro.”

http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=3&p_RefId=129&p_IsPs=Y

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Cannabis may help stroke recovery

“CANNABIS may help to reduce brain damage after a stroke, new research suggests.

Chemical compounds found in the plant could help shrink the area of the brain affected by stroke, the study says.

Cannabinoids in the plant, as well as those that can be made artificially and those found naturally in the body, can also help improve brain function after a stroke attack, the authors said.

The study, which is to be presented to the annual UK Stroke Forum, examined previous studies conducted on the effect of the compound.

The authors, from the University of Nottingham, examined 94 studies evaluating the effects of cannabinoids on 1022 male rats, mice or monkeys.

They say the chemical “shows promise as a neuroprotective treatment for stroke”.

“This meta-analysis of pre-clinical stroke studies provides valuable information on the existing, and importantly, missing data on the use of cannabinoids as a potential treatment for stroke patients,” said lead author Dr Tim England, honorary consultant stroke physician at the University of Nottingham and Royal Derby Hospital.

Dr Dale Webb, director of research and information at the Stroke Association, added: “Stroke is the leading cause of adult disability in the UK, with more than half of all stroke survivors left dependent on others for everyday activities. With more people in the UK surviving a stroke, it’s never been more important to find new treatments to help more stroke patients make better recoveries.

“This new research is an example of the many new developments in the field of stroke which are being presented at this year’s UK Stroke Forum.

“The findings have identified the potential for cannabinoids to reduce brain damage caused by stroke.”

http://www.news.com.au/world/breaking-news/cannabis-may-help-stroke-recovery/story-e6frfkui-1226774100340

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Chemicals in Marijuana May Help Stroke Victims

NewsBriefs

“Scientists at the National Institute of Mental Health (NIMH) said a chemical in marijuana may protect the brain from damage inflicted by a stroke.

Their study was reported in the Proceedings of the National Academy of Sciences (Aidan Hampson, et al., “Cannabidiol and Delta-9-tetrahydrocannabinol Are Neuroprotective Antioxidants,” Proceedings of the National Academy of Sciences, July 7, 1998, Vol. 95, Issue 14, p. 8268; “Pot Chemicals Might Inhibit Breast Tumors, Stroke Damage,” Dallas Morning News, July 13, 1998; Vanessa Thorpe, “Chemicals Help Brain Damage After Stroke,” The Independent (UK), July 19, 1998).

NIMH scientists researched the effects of two cannabinoids, cannabidiol and THC, on the brains of rats. THC is the ingredient in marijuana that causes a psychoactive effect. However, cannabidiol is “a better candidate,” in part, because it does not cause a “high” in the patient, said Aidan Hampson, a neuropharmacologist at NIMH who led the study.

The cannabinoids block a neurochemical, known as glutamate, that leads to the formation of toxic oxidizing molecules that kill brain cells. Glutamate is produced in the brain if the oxygen supply is cut off, for example, as the result of blood clot leading to a stroke.

Researchers found that cannabidiol is a more effective antioxidant than vitamins A and E, which already are known to block the damaging effects of glutamate.”

http://www.ndsn.org/julaug98/medmj1.html

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Cannabis Counter Brain Cell Damage After a Stroke

“New research by University of Otago scientists suggests some mechanisms in the brain targeted by cannabis could become drugs targets to counter brain cell damage after a stroke.

Researchers from the Medical School’s Department of Pharmacology and Toxicology have been the first in the world to show the cannabinoid CB2 receptor appears in the rat brain following a stroke.

Their findings were published recently in the journal Neuroscience Letters.

Dr John Ashton says the CB2 receptor is a protein produced as part of the body’s immune response system.

“This response is triggered by stroke and causes the inflammation that leads to damage in the area of the brain around where the stroke has occurred.

“If the inflammation can be stopped or reduced then it offers the hope of reducing the extent of the damage caused by stroke – and CB2 offers a potential target for such a drug.”

Dr Ashton says cannabis targets both the CB2 and the related CB1 receptors.

“THC, the major active ingredient of cannabis, acts mainly on CB1 but it also affects CB2. While THC is known to have some positive effects in terms of pain management its use is severely limited because of the way it triggers the psychoactive CB1 receptors in the brain,” he says.

“The aim would be to develop a drug that targets the CB2 receptor without affecting CB1.”

Dr Ashton says the relationship between cannabis and cannabinoid drugs has similarities to the relationship between heroin and codeine.

“Heroin and codeine share common targets, but by designing codeine in such a way that it eliminated the psychoactive side-effects seen with heroin, a therapeutically useful drug was developed. There is the potential to do the same with cannabinoids.”

Drugs targeting CB2 could also have potential therapeutic use in other conditions involving inflammatory damage to the brain, such as Huntington’s Disease and Alzheimer’s Disease. There may also be scope to use them in pain management.

“CB2 cells are also found in the spinal cord. They regulate pain signals making them a potential target for new pain killing drugs.”"

http://www.hightimes.com/read/cannabis-counter-brain-cell-damage-after-stroke

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Cannabis compounds may limit stroke damage

“Chemical compounds found in cannabis may help to reduce brain damage following a stroke, new research has revealed.

Researchers at the University of Nottingham conducted a meta-analysis of experimental studies into cannabinoids; chemicals related to those found in cannabis, some of which also occur naturally in the body.

The findings showed that the compounds could reduce the size of stroke and improve .

Cannabinoids can be classified into those found naturally in the body (endocannabinoids), those made artificially (synthetic cannabinoids) or those derived from extracts from the plant cannabis sativa (phytocannabinoids).

The research, announced at the annual UK Stroke Forum, indicates that all three classes of cannabinoid could be effective in shrinking the area of the brain affected by stroke and in recovering neurological function.”

http://healthmedicinet.com/i/cannabis-compounds-may-limit-stroke-damage/

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Compounds in cannabis could limit stroke damage

“Researchers at the University of Nottingham conducted a meta-analysis of experimental studies into cannabinoids; chemicals related to those found in cannabis, some of which also occur naturally in the body.

The findings showed that the compounds could reduce the size of stroke and improve neurological function.”

http://www.myscience.org.uk/news/2013/compounds_in_cannabis_could_limit_stroke_damage-2013-nottingham

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