is·che·mi·aQuote:
Originally Posted by example 1Marijuana and related drugs (cannabinoids) have been proposed as treatments for a widening spectrum of medical disorders. R(+)-[2, 3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1, 4-benzoxazin-yl]-(1-naphthalenyl)methanone mesylate (R(+)-WIN 55212-2), a synthetic cannabinoid agonist, decreased hippocampal neuronal loss after transient global cerebral ischemia and reduced infarct volume after permanent focal cerebral ischemia induced by middle cerebral artery occlusion in rats. The less active enantiomer S(-)-WIN 55212-3 was ineffective, and the protective effect of R(+)-WIN 55212-2 was blocked by the specific central cannabinoid (CB1) cannabinoid receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide-hydrochloride. R(+)-WIN 55212-2 also protected cultured cerebral cortical neurons from in vitro hypoxia and glucose deprivation, but in contrast to the receptor-mediated neuroprotection observed in vivo, this in vitro effect was not stereoselective and was insensitive to CB1 and CB2 receptor antagonists. Cannabinoids may have therapeutic potential in disorders resulting from cerebral ischemia, including stroke, and may protect neurons from injury through a variety of mechanisms. http://www.erowid.org/references/refs_view.php?ID=6198
n.
A decrease in the blood supply to a bodily organ, tissue, or part caused by constriction or obstruction of the blood vessels.
hy·pox·i·a
n.
Deficiency in the amount of oxygen reaching body tissues.
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Originally Posted by example 2A cannabinoid derivative, dexanabinol (HU-211), could be the first neuroprotective agent to be approved for human use.
...it blocks glutamate-induced neurotoxicity; it scavenges both peroxy and hydroxy free-radicals; and it inhibits the action of the inflammatory cytokine alpha-tumour necrosis factor. "The triple action stops the spread of the primary neuronal damage from the core of injury to the surrounding brain tissue, even after a single intravenous injection, up to 6 hours after the initial insult", says Raphael Mechoulam, professor of pharmacology, Hadassah Medical School, Jerusalem, Israel.
http://www.erowid.org/plants/cannabi...t_1_text.shtml
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Originally Posted by example 3We tested cannabinoid receptor agonists for effects on excitatory neurotransmission between cultured rat hippocampal neurons.
Thus, activation of cannabinoid receptors inhibits the presynaptic release of glutamate via an inhibitory G-protein.
http://www.erowid.org/references/refs_view.php?ID=6185
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Originally Posted by example 4...we tested several cannabimimetics in a model of synaptically mediated neuronal death.
The cannabimimetic drug Win55212-2 (100 nM) completely blocked [Ca2+]i spiking and prevented neuronal death induced by low extracellular Mg2+ concentrations. These effects on [Ca2+]i spiking and viability were stereoselective and were prevented by the CB1 receptor antagonist SR141716 (100 nM). The partial agonist CP55940 (100 nM) also afforded significant protection from excitotoxicity. Cannabimimetic drugs did not protect cells from the direct application of glutamate (30 microM). These data suggest that cannabimimetic drugs may slow the progression of neurodegenerative diseases.
http://www.erowid.org/references/refs_view.php?ID=6192
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Originally Posted by example 5Excitotoxicity is a paradigm used to explain the biochemical events in both acute neuronal damage and in slowly progressive, neurodegenerative diseases. Here, we show in a longitudinal magnetic resonance imaging study that Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the main active compound in marijuana, reduces neuronal injury in neonatal rats injected intracerebrally with the Na(+)/K(+)-ATPase inhibitor ouabain to elicit excitotoxicity.
After 7 d, 36% less neuronal damage was observed in treated rats compared with control animals.
Coadministration of the CB(1) cannabinoid receptor antagonist SR141716 prevented the neuroprotective actions of Delta(9)-THC, indicating that Delta(9)-THC afforded protection to neurons via the CB(1) receptor. In Delta(9)-THC-treated rats the volume of astrogliotic tissue was 36% smaller. The CB(1) receptor antagonist did not block this effect.
These results provide evidence that the cannabinoid system can serve to protect the brain against neurodegeneration.
http://www.erowid.org/references/refs_view.php?ID=6193
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Originally Posted by example 6The formation of the endocannabinoids anandamide and 2-arachidonoyl glycerol is strongly enhanced after brain injury, and there is evidence that these compounds reduce the secondary damage incurred. Some plant and synthetic cannabinoids, which do not bind to the cannabinoid receptors, have also been shown to be neuroprotective, possibly through their direct effect on the excitatory glutamate system and/or as antioxidants.
http://www.erowid.org/references/refs_view.php?ID=1327
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Originally Posted by example 7Type 1 vanilloid receptors (VR1) have been identified recently in the brain, in which they serve as yet primarily undetermined purposes. The endocannabinoid anandamide (AEA) and some of its oxidative metabolites are ligands for VR1, and AEA has been shown to afford protection against ouabain-induced in vivo excitotoxicity, in a manner that is only in part dependent on the type 1 cannabinoid (CB1) receptor.
Using magnetic resonance imaging we show the following: (1) pretreatment with the reduced 12-lipoxygenase metabolite of AEA, 12-HAEA, attenuated cytotoxic edema formation in a CB1 receptor-independent manner in the acute phase after intracranial injection of the Na+/K+-ATPase inhibitor ouabain; (2) the reduced 15-lipoxygenase metabolite, 15-HAEA, enhanced the neuroprotective effect of AEA in the acute phase; (3) modulation of VR1, as tested using arvanil, the VR1 agonist capsaicin, and the antagonist capsazepine, leads to neuroprotective effects in this model, and arvanil is a potent neuroprotectant, acting at both CB1 and VR1; and (4) the in vivo neuroprotective effects of AEA are mediated by CB1 but not by lipoxygenase metabolites or VR1.
http://www.erowid.org/references/refs_view.php?ID=6197
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Originally Posted by example 8We generated conditional mutant mice that lack expression of the cannabinoid receptor type 1 in principal forebrain neurons but not in adjacent inhibitory interneurons. In mutant mice,the excitotoxin kainic acid (KA) induced excessive seizures in vivo.
The threshold to KA-induced neuronal excitation in vitro was severely reduced in hippocampal pyramidal neurons of mutants. KA administration rapidly raised hippocampal levels of anandamide and induced protective mechanisms in wild-type principal hippocampal neurons. These protective mechanisms could not be triggered in mutant mice. The endogenous cannabinoid system thus provides on-demand protection against acute excitotoxicity in central nervous system neurons.
http://www.erowid.org/references/refs_view.php?ID=6199
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Originally Posted by example 9Dexanabinol, HU-211, a synthetic cannabinoid devoid of psychotropic effects, improves neurological outcome in models of brain trauma, ischemia and meningitis. Recently, HU-211 was found to inhibit brain tumor necrosis factor (TNFalpha) production after head injury.
http://www.erowid.org/references/refs_view.php?ID=6191
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Originally Posted by example 10Research at the Hebrew University in Israel, reported in the journal Nature, shows that a cannabinoid, similar to the active ingredient found in marijuana and produced in the brains of many animals, protects mice from brain injury.
Mice that sustained brain injuries were discovered to have elevated levels of a compound known as 2-Arachodonoyl glycerol, or 2-AG. Theorizing that this cannabinoid was produced to prevent damage, the researchers administered more of the compound to injured mice and found it protected the brain.
http://www.a1b2c3.com/drugs/mj021.htm
I, just, don't know what to say.Quote:
Originally Posted by example 11Dexanabinol, a synthetic drug, is derived from the active agent in cannabis, or marijuana. It acts on the so-called secondary injury process, which is a chemical cascade that leads to progressive brain cell death after the initial trauma. The drug counters inflammation, works as an antioxidant and blocks the uncontrolled influx of calcium into the cells, which can kill them.
http://www.post-gazette.com/healthsc...head0701p1.asp
I base a lot of stuff on rats.
