PMID- 29886251
OWN - NLM
STAT- MEDLINE
DCOM- 20190927
LR  - 20191210
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1697
DP  - 2018 Oct 15
TI  - A cannabinoid receptor 2 agonist reduces blood-brain barrier damage via induction 
      of MKP-1 after intracerebral hemorrhage in rats.
PG  - 113-123
LID - S0006-8993(18)30333-0 [pii]
LID - 10.1016/j.brainres.2018.06.006 [doi]
AB  - BACKGROUND AND PURPOSE: The blood-brain barrier (BBB) disruption and the 
      following development of brain edema, is the most life-threatening secondary 
      injury after intracerebral hemorrhage (ICH). This study is to investigate a 
      potential role and mechanism of JWH133, a selected cannabinoid receptor type2 
      (CB2R) agonist, on protecting blood-brain barrier integrity after ICH. METHODS: 
      192 adult male Sprague-Dawley (SD) rats were randomly divided into Sham; 
      ICH + Vehicle; ICH + JWH 1.0 mg/kg, ICH + JWH 1.5 mg/kg and ICH + JWH 2.0 mg/kg; 
      ICH + SR + JWH respectively. Animals were euthanized at 24 h following western 
      blots and immunofluorescence staining, we also examined the effect of JWH133 on 
      the brain water contents, neurobehavioral deficits and blood brain barrier (BBB) 
      permeability, meanwhile reassessed the inflammatory cytokines concentrations 
      around the hematoma by enzyme-linked immunosorbent assay (ELISA) in each group. 
      RESULTS: JWH133 (1.5 mg/kg) administration ameliorated brain edema, neurological 
      deficits and blood-brain barrier damage, as well as microglia activation. The 
      expression of pro-inflammatory mediators interleukin 1beta (IL-1beta), interleukin-6 
      (IL-6), tumor necrosis factor-alpha (TNF-alpha) and matrix metallopeptidase-2/9 (MMP2/9) 
      were attenuated, but not monocyte chemoattractant protein-1 (MCP-1). 
      Additionally, decreases in zonula occludens-1 (ZO-1) and claudin-5 expression 
      were partially recovered by JWH133. Furthermore, JWH133 upregulated the 
      expression level of MKP-1, which leads to the inhibition of MAPKs signaling 
      pathway activation, especially for ERK and P38. However, these effects were 
      reversed by pretreatment with a selective CB2R antagonist, SR144528. CONCLUSIONS: 
      CB2R agonist alleviated neuroinflammation and protected blood-brain barrier 
      permeability in a rat ICH model. Further molecular mechanisms revealed which is 
      probably mediated by enhancing the expression of MKP-1, then inhibited MAPKs 
      signal transduction.
CI  - Copyright (c) 2018. Published by Elsevier B.V.
FAU - Li, Lin
AU  - Li L
AD  - Department of Neurosurgery, Nanchong Central Hospital, Nanchong 637000, China.
FAU - Yun, Debo
AU  - Yun D
AD  - Department of Neurosurgery, Nanchong Central Hospital, Nanchong 637000, China.
FAU - Zhang, Yuan
AU  - Zhang Y
AD  - Department of Neurosurgery, Nanchong Central Hospital, Nanchong 637000, China.
FAU - Tao, Yihao
AU  - Tao Y
AD  - Department of Neurosurgery, Southwest Hospital, Third Military Medical 
      University, Chongqing 400038, China.
FAU - Tan, Qiang
AU  - Tan Q
AD  - Department of Neurosurgery, Southwest Hospital, Third Military Medical 
      University, Chongqing 400038, China.
FAU - Qiao, Fei
AU  - Qiao F
AD  - Department of Neurosurgery, Nanchong Central Hospital, Nanchong 637000, China.
FAU - Luo, Bo
AU  - Luo B
AD  - Department of Neurosurgery, Nanchong Central Hospital, Nanchong 637000, China.
FAU - Liu, Yi
AU  - Liu Y
AD  - Department of Neurosurgery, Nanchong Central Hospital, Nanchong 637000, China.
FAU - Fan, Runjin
AU  - Fan R
AD  - Department of Neurosurgery, Nanchong Central Hospital, Nanchong 637000, China.
FAU - Xian, Jishu
AU  - Xian J
AD  - Department of Neurosurgery, Southwest Hospital, Third Military Medical 
      University, Chongqing 400038, China. Electronic address: lilin025683@sina.com.
FAU - Yu, Anyong
AU  - Yu A
AD  - Department of Emergency, The First Affiliated Hospital of Zunyi Medical College, 
      Guizhou 563003, China. Electronic address: anyongyu@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180607
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Camphanes)
RN  - 0 (Cannabinoids)
RN  - 0 (Cnr2 protein, rat)
RN  - 0 (Cytokines)
RN  - 0 (Pyrazoles)
RN  - 0 (Receptor, Cannabinoid, CB2)
RN  - 0 (SR 144528)
RN  - EC 3.1.3.48 (Dual Specificity Phosphatase 1)
RN  - EC 3.1.3.48 (Dusp1 protein, rat)
RN  - TDG8048RDA (1,1-dimethylbutyl-1-deoxy-Delta(9)-THC)
SB  - IM
MH  - Animals
MH  - Biological Transport
MH  - Blood-Brain Barrier/drug effects
MH  - Brain/metabolism/pathology
MH  - Brain Edema/drug therapy/*pathology
MH  - Camphanes/pharmacology
MH  - Cannabinoids/*metabolism/pharmacology
MH  - Cerebral Hemorrhage/pathology
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Dual Specificity Phosphatase 1/metabolism/physiology
MH  - Male
MH  - Permeability
MH  - Pyrazoles/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Cannabinoid, CB2/agonists/*metabolism
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - Blood-brain barrier
OT  - Cannabinoid receptor type 2
OT  - Intracerebral hemorrhage
OT  - MKP-1
OT  - Neuroinflammation
EDAT- 2018/06/11 06:00
MHDA- 2019/09/29 06:00
CRDT- 2018/06/11 06:00
PHST- 2018/02/01 00:00 [received]
PHST- 2018/05/30 00:00 [revised]
PHST- 2018/06/05 00:00 [accepted]
PHST- 2018/06/11 06:00 [pubmed]
PHST- 2019/09/29 06:00 [medline]
PHST- 2018/06/11 06:00 [entrez]
AID - S0006-8993(18)30333-0 [pii]
AID - 10.1016/j.brainres.2018.06.006 [doi]
PST - ppublish
SO  - Brain Res. 2018 Oct 15;1697:113-123. doi: 10.1016/j.brainres.2018.06.006. Epub 
      2018 Jun 7.