Modulation of the balance between cannabinoid CB1 and CB2 receptor activation during cerebral ischemic/reperfusion injury

Zhang, Ming; Martin, Billy R.; Adler, Martin W.; Razdan, Raj K.; Ganea, Doina; Tuma, Ronald F.

doi:10.1016/j.neuroscience.2008.01.022

Cited by 112 publications

(113 citation statements)

References 45 publications

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“…As far as the cannabinoid receptors are concerned, most studies showed an upregulated expression of both CB 1 R and, in particular, CB 2 R in stroke, with neurons (for CB 1 R) and microglial/macrophages, astrocytes, and neutrophils (for CB 2 R) being the most common cellular substrates for these responses [33,[51][52][53][54]. However, some studies described downregulatory responses of both receptors at very early times after induction of ischemia [33,55]. Upregulation of CB 2 R with no changes in CB 1 R have been found in TBI [56].…”

Section: Cannabinoids and Acute Brain Damage: Stroke And Brain Traumamentioning

confidence: 99%

Cannabinoids in Neurodegenerative Disorders and Stroke/Brain Trauma: From Preclinical Models to Clinical Applications

2015

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Cannabinoids form a singular family of plantderived compounds (phytocannabinoids), endogenous signaling lipids (endocannabinoids), and synthetic derivatives with multiple biological effects and therapeutic applications in the central and peripheral nervous systems. One of these properties is the regulation of neuronal homeostasis and survival, which is the result of the combination of a myriad of effects addressed to preserve, rescue, repair, and/or replace neurons, and also glial cells against multiple insults that may potentially damage these cells. These effects are facilitated by the location of specific targets for the action of these compounds (e.g., cannabinoid type 1 and 2 receptors, endocannabinoid inactivating enzymes, and nonendocannabinoid targets) in key cellular substrates (e.g., neurons, glial cells, and neural progenitor cells). This potential is promising for acute and chronic neurodegenerative pathological conditions. In this review, we will collect all experimental evidence, mainly obtained at the preclinical level, supporting that different cannabinoid compounds may be neuroprotective in adult and neonatal ischemia, brain trauma, Alzheimer's disease, Parkinson's disease, Huntington's chorea, and amyotrophic lateral sclerosis. This increasing experimental evidence demands a prompt clinical validation of cannabinoid-based medicines for the treatment of all these disorders, which, at present, lack efficacious treatments for delaying/arresting disease progression, despite the fact that the few clinical trials conducted so far with these medicines have failed to demonstrate beneficial effects.

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Section: Cannabinoids and Acute Brain Damage: Stroke And Brain Traumamentioning

confidence: 99%

Cannabinoids in Neurodegenerative Disorders and Stroke/Brain Trauma: From Preclinical Models to Clinical Applications

2015

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“…No signal changes were observed at early timepoints (4 h after stroke). [ 18 F]MK-9470 PET is thus a promising in vivo tool for the study of the effects of new drugs that target the endocannabinoid system in the subacute phase after stroke [13]. The increased CB 1 binding at these time-points was confirmed by immunohistochemical analysis.…”

Section: Discussionmentioning

confidence: 84%

“…We characterized changes in both CB 1 and CB 2 for the first time in vivo in a rat model of stroke by small-animal PET using [ Whole-brain characterization of CB 1 /CB 2 in stroke could be used in the proof-of-principle mechanistic investigation of potential pharmacological treatment approaches [13].…”

Section: Discussionmentioning

confidence: 99%

“…Our findings are thus in line with those of this previous ex vivo study, although no increased CB 1 binding was detected 3.5 h after stroke induction. Zhang et al evaluated the expression of CB 1 by real-time PCR in the ischaemic hemisphere in a mouse model with transient MCAO from 1 h after ischaemia [13]. CB 1 mRNA levels were measured at different time-points up to 24 h after MCAO, and showed a maximal increase at 6 h. There seems to be a delay between mRNA expression and increased binding observed in this model.…”

Section: Discussionmentioning

confidence: 99%

“…This progress is associated with decreased leucocyte/endothelial cell interactions. Moreover, the combination of a CB 1 antagonist (SR141716) and a CB 2 agonist (O-1966) provided an even higher level of protection in ischaemia by increasing the regional cerebral blood flow during ischaemia [12,13]. Furthermore, Murikinati et al showed that administration of the CB 2 agonist JWH-133 decreases infarct size in a mouse model of ischaemic stroke by inhibiting neutrophil recruitment to the brain [14].…”

Section: Introductionmentioning

confidence: 99%

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Small-animal PET imaging of the type 1 and type 2 cannabinoid receptors in a photothrombotic stroke model

Vandeputte

Casteels

Struys

et al. 2012

Eur J Nucl Med Mol Imaging

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Purpose Recent ex vivo and pharmacological evidence suggests involvement of the endocannabinoid system in the pathophysiology of stroke, but conflicting roles for type 1 and 2 cannabinoid receptors (CB 1 and CB 2 ) have been suggested. The purpose of this study was to evaluate CB 1 and CB 2 receptor binding over time in vivo in a rat photothrombotic stroke model using PET. Methods CB 1 and CB 2 microPET imaging was performed at regular time-points up to 2 weeks after stroke using [18 F] MK-9470 and [11 C]NE40. Stroke size was measured using MRI at 9.4 T. Ex vivo validation was performed via immunostaining for CB 1 and CB 2 . Immunofluorescent double stainings were also performed with markers for astrocytes (GFAP) and macrophages/microglia (CD68). Results [18 F]MK-9470 PET showed a strong increase in CB 1 binding 24 h and 72 h after stroke in the cortex surrounding the lesion, extending to the insular cortex 24 h after surgery. These alterations were consistently confirmed by CB 1 immunohistochemical staining. [11 C]NE40 did not show any significant differences between stroke and sham-operated animals, although staining for CB 2 revealed minor immunoreactivity at 1 and 2 weeks after stroke in this model. Both CB 1 + and CB 2 + cells showed minor immunoreactivity for CD68. Conclusion Time-dependent and regionally strongly increased CB 1 , but not CB 2 , binding are early consequences of photothrombotic stroke. Pharmacological interventions should primarily aim at CB 1 signalling as the role of CB 2 seems minor in the acute and subacute phases of stroke.

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The Cerebral Microcirculation

Tuma

2008

Comprehensive Physiology

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Modulation of the balance between cannabinoid CB1 and CB2 receptor activation during cerebral ischemic/reperfusion injury

Cited by 112 publications

References 45 publications

Cannabinoids in Neurodegenerative Disorders and Stroke/Brain Trauma: From Preclinical Models to Clinical Applications

Cannabinoids in Neurodegenerative Disorders and Stroke/Brain Trauma: From Preclinical Models to Clinical Applications

Small-animal PET imaging of the type 1 and type 2 cannabinoid receptors in a photothrombotic stroke model

The Cerebral Microcirculation

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