PMID- 22020035
OWN - NLM
STAT- MEDLINE
DCOM- 20120814
LR  - 20210105
IS  - 1524-4628 (Electronic)
IS  - 0039-2499 (Linking)
VI  - 43
IP  - 1
DP  - 2012 Jan
TI  - Cannabinoid type 2 receptor activation downregulates stroke-induced classic and 
      alternative brain macrophage/microglial activation concomitant to 
      neuroprotection.
PG  - 211-9
LID - 10.1161/STROKEAHA.111.631044 [doi]
AB  - BACKGROUND AND PURPOSE: Ischemic stroke continues to be one of the main causes of 
      death worldwide. Inflammation accounts for a large part of damage in this 
      pathology. The cannabinoid type 2 receptor (CB2R) has been proposed to have 
      neuroprotective properties in neurological diseases. Therefore, our aim was to 
      determine the effects of the activation of CB2R on infarct outcome and on 
      ischemia-induced brain expression of classic and alternative markers of 
      macrophage/microglial activation. METHODS: Swiss wild-type and CB2R knockout male 
      mice were subjected to a permanent middle cerebral artery occlusion. Mice were 
      treated with either a CB2R agonist (JWH-133), with or without a CB2R antagonist 
      (SR144528) or vehicle. Infarct outcome was determined by measuring infarct volume 
      and neurological outcome. An additional group of animals was used to assess mRNA 
      and protein expression of CB2R, interleukin (IL)-1beta, IL-6, tumor necrosis factor 
      alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory 
      peptide (MIP) -1alpha, RANTES, inducible nitric oxide synthase (iNOS), 
      cyclooxygenase-2, IL-4, IL-10, transforming growth factor beta (TGF-beta), arginase I, 
      and Ym1. RESULTS: Administration of JWH-133 significantly improved infarct 
      outcome, as shown by a reduction in brain infarction and neurological impairment. 
      This effect was reversed by the CB2R antagonist and was absent in CB2R knockout 
      mice. Concomitantly, administration of JWH-133 led to a lower intensity of Iba1+ 
      microglia/macrophages and a decrease in middle cerebral artery occlusion-induced 
      gene expression of both classic (IL-6, TNF-alpha, MCP-1, MIP-1alpha, RANTES, and iNOS) 
      and alternative mediators/markers (IL-10, TGF-beta, and Ym1) of 
      microglial/macrophage activation after permanent middle cerebral artery 
      occlusion. CONCLUSIONS: The inhibitory effect of CB2R on the activation of 
      different subpopulations of microglia/macrophages may account for the protective 
      effect of the selective CB2R agonist JWH-133 after stroke.
FAU - Zarruk, Juan G
AU  - Zarruk JG
AD  - Unidad de Investigacio n Neurovascular, Dpto. Farmacologia, Facultad Medicina, 
      Universidad Complutense (UCM), Madrid, Spain.
FAU - Fernandez-Lopez, David
AU  - Fernandez-Lopez D
FAU - Garcia-Yebenes, Isaac
AU  - Garcia-Yebenes I
FAU - Garcia-Gutierrez, Maria S
AU  - Garcia-Gutierrez MS
FAU - Vivancos, Jose
AU  - Vivancos J
FAU - Nombela, Florentino
AU  - Nombela F
FAU - Torres, Magdalena
AU  - Torres M
FAU - Burguete, Maria C
AU  - Burguete MC
FAU - Manzanares, Jorge
AU  - Manzanares J
FAU - Lizasoain, Ignacio
AU  - Lizasoain I
FAU - Moro, Maria A
AU  - Moro MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111020
PL  - United States
TA  - Stroke
JT  - Stroke
JID - 0235266
RN  - 0 (Camphanes)
RN  - 0 (Cannabinoids)
RN  - 0 (Cytokines)
RN  - 0 (Pyrazoles)
RN  - 0 (Receptor, Cannabinoid, CB2)
RN  - 0 (SR 144528)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - TDG8048RDA (1,1-dimethylbutyl-1-deoxy-Delta(9)-THC)
SB  - IM
MH  - Animals
MH  - Brain/drug effects/*metabolism/pathology
MH  - Camphanes/pharmacology
MH  - Cannabinoids/pharmacology
MH  - Cyclooxygenase 2/metabolism
MH  - Cytokines/metabolism
MH  - Down-Regulation/drug effects
MH  - Infarction, Middle Cerebral Artery/*metabolism/pathology
MH  - Macrophages/drug effects/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Microglia/drug effects/*metabolism/pathology
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Pyrazoles/pharmacology
MH  - Receptor, Cannabinoid, CB2/genetics/*metabolism
EDAT- 2011/10/25 06:00
MHDA- 2012/08/15 06:00
CRDT- 2011/10/25 06:00
PHST- 2011/10/25 06:00 [entrez]
PHST- 2011/10/25 06:00 [pubmed]
PHST- 2012/08/15 06:00 [medline]
AID - STROKEAHA.111.631044 [pii]
AID - 10.1161/STROKEAHA.111.631044 [doi]
PST - ppublish
SO  - Stroke. 2012 Jan;43(1):211-9. doi: 10.1161/STROKEAHA.111.631044. Epub 2011 Oct 
      20.