PMID- 24939000
OWN - NLM
STAT- MEDLINE
DCOM- 20150511
LR  - 20181202
IS  - 1097-4547 (Electronic)
IS  - 0360-4012 (Linking)
VI  - 92
IP  - 11
DP  - 2014 Nov
TI  - GluN2B N-methyl-D-aspartic acid receptor subunit mediates atorvastatin-Induced 
      neuroprotection after focal cerebral ischemia.
PG  - 1529-48
LID - 10.1002/jnr.23426 [doi]
AB  - Statins are potent cholesterol biosynthesis inhibitors that exert protective 
      effects in humans and in experimental models of stroke. The mechanisms involved 
      in these protective actions are not completely understood. This study evaluates 
      whether atorvastatin (ATV) treatment affects the GluN1 and GluN2B subunits of the 
      N-methyl-D-aspartic acid receptor in the somatosensory cerebral cortex at short 
      and long periods following ischemia. Sham and ischemic male Wistar rats received 
      10 mg/kg of ATV or placebo by gavage every 24 hr for 3 consecutive days. The 
      first dose was administered 6 hr after ischemia-reperfusion or the sham 
      operation. ATV treatment resulted in faster recovery of neurological scores than 
      placebo, prevented the appearance of pyknotic neurons, and restored 
      microtubule-associated protein 2 and neuronal nuclei staining to control values 
      in the somatosensory cerebral cortex and the hippocampus at 72 hr and 15 days 
      postischemia. Furthermore, ATV prevented spatial learning and memory deficits 
      caused by cerebral ischemia. Cerebral ischemia reduced the number of GluN1/PSD-95 
      and GluN2B/PSD-95 colocalization clusters in cortical pyramidal neurons and 
      reduced the levels of brain-derived neurotrophic factor (BDNF) in the cerebral 
      cortex. These effects of the ischemic insult were prevented by ATV, which also 
      induced GluN2B/PSD-95 colocalization in neuronal processes and an association of 
      GluN2B with TrkB. The GluN2B pharmacological inhibitor ifenprodil prevented the 
      increase in BDNF levels and the motor and cognitive function recovery caused by 
      ATV in ischemic rats. These findings indicate that GluN2B is involved in the 
      neuroprotective mechanism elicited by ATV to promote motor and cognitive recovery 
      after focal cerebral ischemia.
CI  - Copyright (c) 2014 Wiley Periodicals, Inc.
FAU - Gutierrez-Vargas, Johanna Andrea
AU  - Gutierrez-Vargas JA
AD  - Cellular and Molecular Neurobiology Area, Group of Neuroscience of Antioquia, 
      Faculty of Medicine, SIU, University of Antioquia, Medellin, Colombia.
FAU - Munoz-Manco, Juan Ignacio
AU  - Munoz-Manco JI
FAU - Garcia-Segura, Luis Miguel
AU  - Garcia-Segura LM
FAU - Cardona-Gomez, Gloria Patricia
AU  - Cardona-Gomez GP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140617
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Heptanoic Acids)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Piperidines)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Pyrroles)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - A0JWA85V8F (Atorvastatin)
RN  - R8OE3P6O5S (ifenprodil)
SB  - IM
MH  - Animals
MH  - Anticholesteremic Agents/pharmacology/*therapeutic use
MH  - Atorvastatin
MH  - Brain Ischemia/complications/*drug therapy/pathology
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Disease Models, Animal
MH  - Embryo, Mammalian
MH  - Heptanoic Acids/pharmacology/*therapeutic use
MH  - Male
MH  - Maze Learning
MH  - Nerve Tissue Proteins/metabolism
MH  - Nervous System Diseases/drug therapy/etiology
MH  - Piperidines/pharmacology/therapeutic use
MH  - Platelet Aggregation Inhibitors/pharmacology/therapeutic use
MH  - Pyrroles/pharmacology/*therapeutic use
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, N-Methyl-D-Aspartate/genetics/*metabolism
MH  - Recovery of Function/drug effects
MH  - Somatosensory Cortex/drug effects
MH  - Time Factors
OTO - NOTNLM
OT  - BDNF
OT  - atorvastatin
OT  - cerebral ischemia, GluN2B
OT  - neuroprotection
OT  - synaptic plasticity
EDAT- 2014/06/19 06:00
MHDA- 2015/05/12 06:00
CRDT- 2014/06/19 06:00
PHST- 2014/03/30 00:00 [received]
PHST- 2014/05/04 00:00 [revised]
PHST- 2014/05/07 00:00 [accepted]
PHST- 2014/06/19 06:00 [entrez]
PHST- 2014/06/19 06:00 [pubmed]
PHST- 2015/05/12 06:00 [medline]
AID - 10.1002/jnr.23426 [doi]
PST - ppublish
SO  - J Neurosci Res. 2014 Nov;92(11):1529-48. doi: 10.1002/jnr.23426. Epub 2014 Jun 
      17.