I'm not sure what this is saying, ask your researchers if this is good or bad news. Inhibiting glutamate release sounds like hyperacute therapy to me.
http://www.biomedcentral.com/content/pdf/1476-511X-9-47.pdf
Background
During the last decade numerous studies have addressed
the role of the endocannabinoid (eCB) system in different
pathological conditions. Endocannabinoids (eCBs), e.g.
anandamide (AEA) and 2-arachidonoylglycerol (2-AG),
are lipid mediators synthesized "on demand" that inhibit
neurotransmitter (glutamate and GABA) release and
modulate neuroinflammation by activating specific CB1
(highly expressed in the CNS, where they mediate the
psychotropic effects of Δ9-tetrahydrocannabinol) and
CB2 (expressed by immune cells, including brain resident
microglial cells) receptors, respectively. Cannabinoid
receptor-inactive eCB-related molecules, e.g. palmitoylethanolamide
(PEA), also exert neuroprotective effects[1-
3], presumably by preventing mast cell degranulation [4],
and directly activating peroxisome proliferator-activated
receptor (PPAR)-α [5], or by enhancing the effects of
AEA on cannabinoid receptors, transient receptor potential
vanilloid type-1 (TRPV1) channels and PPAR-γ
receptors [6].
Previous murine and cell culture studies on stroke and
hypoxia postulated a neuroprotective role of eCBs, given
their ability to decrease NMDA-mediated toxicity in vascular
penumbra through a CB1-mediated mechanism [7].
Increases of AEA content, of the AEA biosynthetic precursors
(e.g. N-acyl phosphatidylethanolamines), and of
CB1 receptors expression in ischemic brain regions of
murine stroke models have been described [8-11]. CB1
knockout mice develop larger stroke volumes than wildtype
animals, with consequent increased post-stroke disability
and mortality [12]. In addition, CB1 agonist administration
was associated with a decrease of infarct volume
and with an improvement of clinical symptoms in stroketreated
mice [13]. Interestingly, there is evidence that also
low-doses of CB1 receptor antagonists, such as rimonabant,
reduce infarct volume in stroke models [9,10,14,15],
possibly by enhancing TRPV1-mediated actions [14]. It
has been also suggested that part of the neuroprotective
effects of CB1 receptor agonists in stroke is due to their
capability of lowering body temperature, and that CB1, as
opposed to CB2, receptors might otherwise play a counterprotective
role in cerebral ischemia [15].
Indeed, also CB2 receptors have been implicated in the
pathogenesis of stroke. Since such receptors are particularly
expressed on activated microglia and peripheral
immune cells (mastcells, macrophages and lymphocytes),
they may act by modulating the inflammatory response
to stroke [16], which is triggered 24-48 hours after symptoms
onset and is mainly responsible for the delayed neuronal
death [17]. Indeed CB2 agonists administration was
associated with a reduction of infarct volume and neurological
impairment in murine models of stroke and cerebral
ischemia [15,18]. However, such evidence is still
lacking in humans, despite the fact that a single case
report described an increase of AEA and PEA content in
the ischemic hemisphere of a stroke patient [19].
Aim of this study was to evaluate the possible involvement
of the eCB system in stroke patients, by measuring
plasma AEA, 2-AG, and PEA levels in the acute phase of
the disease and by correlating eCB and PEA plasmatic
levels with measures of neurological impairment and volume
of the ischemic brain tissue.
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