PMID- 23500607
OWN - NLM
STAT- MEDLINE
DCOM- 20131115
LR  - 20181202
IS  - 1872-9754 (Electronic)
IS  - 0197-0186 (Linking)
VI  - 62
IP  - 7
DP  - 2013 Jun
TI  - Atorvastatin prevents cell damage via modulation of oxidative stress, glutamate 
      uptake and glutamine synthetase activity in hippocampal slices subjected to 
      oxygen/glucose deprivation.
PG  - 948-55
LID - S0197-0186(13)00074-0 [pii]
LID - 10.1016/j.neuint.2013.03.002 [doi]
AB  - Oxygen-glucose deprivation (OGD) in brain cells increases extracellular glutamate 
      concentration leading to excitotoxicity. Glutamate uptake from the synaptic cleft 
      is carried out by glutamate transporters, which are likely to be modulated by 
      oxidative stress. Therefore, oxidative stress is associated with reduced activity 
      of glutamate transporters and glutamine synthetase, thus increasing extracellular 
      glutamate levels that may aggravate damage to brain cells. Atorvastatin, a 
      cholesterol-lowering agent, has been shown to exert neuroprotective effects. The 
      aim of this study was to investigate if in vivo atorvastatin treatment would have 
      protective effects against hippocampal slices subjected to OGD, ex vivo. 
      Atorvastatin pretreatment promoted increased cell viability after OGD and 
      reoxygenation of hippocampal slices. Atorvastatin-induced neuroprotection may be 
      related to diminished oxidative stress, since it prevented OGD-induced decrement 
      of non-proteic thiols (NPSH) levels and increase in the production of reactive 
      oxygen species (ROS). Atorvastatin pretreatment also prevented the OGD-induced 
      decrease in glutamate uptake and glutamine synthetase activity, although it had 
      no effect on OGD-induced excitatory aminoacids release. Addition of cholesterol 
      before OGD and reoxygenation, abolished the protective effect of atorvastatin on 
      cellular viability as well as on glutamate uptake and glutamine synthetase 
      activity. Therefore, atorvastatin is capable of preventing OGD-induced cell 
      death, an effect achieved due to modulation of glutamate uptake and glutamine 
      synthetase activity, and associated with diminished oxidative stress. 
      Additionally, atorvastatin effects were dependent on its action on cholesterol 
      synthesis inhibition. Thus, atorvastatin might be a useful strategy in the 
      prevention of glutamate exitotoxicity involved in brain injuries such as vascular 
      disorders.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Vandresen-Filho, Samuel
AU  - Vandresen-Filho S
AD  - Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal 
      de Santa Catarina, Trindade, 88040-900 Florianopolis, SC, Brazil.
FAU - Martins, Wagner C
AU  - Martins WC
FAU - Bertoldo, Daniela B
AU  - Bertoldo DB
FAU - Mancini, Gianni
AU  - Mancini G
FAU - Herculano, Bruno A
AU  - Herculano BA
FAU - de Bem, Andreza F
AU  - de Bem AF
FAU - Tasca, Carla I
AU  - Tasca CI
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130314
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 0 (Heptanoic Acids)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Pyrroles)
RN  - 0 (Reactive Oxygen Species)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - A0JWA85V8F (Atorvastatin)
RN  - EC 6.3.1.2 (Glutamate-Ammonia Ligase)
RN  - IY9XDZ35W2 (Glucose)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Atorvastatin
MH  - Cell Death/drug effects
MH  - Glucose/metabolism
MH  - Glutamate-Ammonia Ligase/*metabolism
MH  - Glutamic Acid/drug effects/*metabolism
MH  - Heptanoic Acids/*pharmacology
MH  - Hippocampus/*drug effects
MH  - Male
MH  - Mice
MH  - Neurons/drug effects/metabolism
MH  - Neuroprotective Agents/pharmacology
MH  - Oxidative Stress/*drug effects
MH  - Oxygen/metabolism
MH  - Pyrroles/*pharmacology
MH  - Reactive Oxygen Species/metabolism
EDAT- 2013/03/19 06:00
MHDA- 2013/11/16 06:00
CRDT- 2013/03/19 06:00
PHST- 2012/07/11 00:00 [received]
PHST- 2013/02/28 00:00 [revised]
PHST- 2013/03/03 00:00 [accepted]
PHST- 2013/03/19 06:00 [entrez]
PHST- 2013/03/19 06:00 [pubmed]
PHST- 2013/11/16 06:00 [medline]
AID - S0197-0186(13)00074-0 [pii]
AID - 10.1016/j.neuint.2013.03.002 [doi]
PST - ppublish
SO  - Neurochem Int. 2013 Jun;62(7):948-55. doi: 10.1016/j.neuint.2013.03.002. Epub 
      2013 Mar 14.