PMID- 24631672
OWN - NLM
STAT- MEDLINE
DCOM- 20141212
LR  - 20140505
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 268
DP  - 2014 May 30
TI  - Ceftriaxone alleviates early brain injury after subarachnoid hemorrhage by 
      increasing excitatory amino acid transporter 2 expression via the PI3K/Akt/NF-kappaB 
      signaling pathway.
PG  - 21-32
LID - S0306-4522(14)00207-3 [pii]
LID - 10.1016/j.neuroscience.2014.02.053 [doi]
AB  - Early brain injury (EBI) after subarachnoid hemorrhage (SAH) is characterized by 
      a reduction in excitatory amino acid transporter 2 (EAAT2) expression and severe 
      amino acid excitotoxicity. The aim of this study was to explore the 
      neuroprotective effect of ceftriaxone (CEF), a potent compound that up-regulates 
      EAAT2, against EBI and the potential mechanisms using in vitro experiments and a 
      rat model of SAH. Intracisternal treatment with CEF significantly improved 
      neurological outcomes and alleviated extracellular glutamate accumulation after 
      SAH. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling 
      assay (TUNEL) staining and Western blot analysis of cleaved caspase 3 showed that 
      CEF decreased hippocampal neuronal apoptosis following SAH. Immunofluorescent 
      staining and Western blotting revealed that CEF significantly reversed the 
      down-regulation of EAAT2 expression following SAH. In Morris water maze (MWM) 
      tests, CEF remarkably ameliorated the SAH-induced cognitive dysfunction in 
      spatial learning memory and reference memory. CEF promoted the nuclear 
      translocation of p65 as well as the activation of Akt in hippocampal astrocytes 
      in vitro and in vivo. These findings suggest that CEF may exert significant 
      protective effects against EBI following SAH by modulating the PI3K/Akt/NF-kappaB 
      signaling pathway.
CI  - Copyright (c) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Feng, D
AU  - Feng D
AD  - Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an 710032, Shaanxi Province, China.
FAU - Wang, W
AU  - Wang W
AD  - Department of Anesthesiology, School of Stomatology, Fourth Military Medical 
      University, Xi'an 710032, Shaanxi Province, China.
FAU - Dong, Y
AU  - Dong Y
AD  - Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an 710032, Shaanxi Province, China; Department of Neurosurgery, 463rd Hospital 
      of PLA, Shenyang 110042, Liaoning Province, China.
FAU - Wu, L
AU  - Wu L
AD  - Department of Biochemistry and Molecular Biology, Fourth Military Medical 
      University, Xi'an 710032, Shaanxi Province, China.
FAU - Huang, J
AU  - Huang J
AD  - Department of Anatomy, Histology and Embryology, Fourth Military Medical 
      University, Xi'an 710032, Shaanxi Province, China.
FAU - Ma, Y
AU  - Ma Y
AD  - Department of Anesthesiology, Xijing Hospital, Fourth Military Medical 
      University, Xi'an 710032, Shaanxi Province, China.
FAU - Zhang, Z
AU  - Zhang Z
AD  - Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an 710032, Shaanxi Province, China.
FAU - Wu, S
AU  - Wu S
AD  - Department of Biochemistry and Molecular Biology, Fourth Military Medical 
      University, Xi'an 710032, Shaanxi Province, China.
FAU - Gao, G
AU  - Gao G
AD  - Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an 710032, Shaanxi Province, China. Electronic address: 
      guodonggao2013@163.com.
FAU - Qin, H
AU  - Qin H
AD  - Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an 710032, Shaanxi Province, China. Electronic address: huaizhouqin@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140312
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Excitatory Amino Acid Transporter 2)
RN  - 0 (NF-kappa B)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nucleocytoplasmic Transport Proteins)
RN  - 0 (Slc1a2 protein, rat)
RN  - 0 (p65 oncofetal mRNA transport protein, rat)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 75J73V1629 (Ceftriaxone)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/physiology
MH  - Astrocytes/drug effects/physiology
MH  - Brain Injuries/*drug therapy/etiology/mortality/physiopathology
MH  - Caspase 3/metabolism
MH  - Ceftriaxone/*pharmacology
MH  - Cells, Cultured
MH  - Cognition Disorders/drug therapy/etiology/physiopathology
MH  - Disease Models, Animal
MH  - Excitatory Amino Acid Transporter 2/*metabolism
MH  - Glutamic Acid/metabolism
MH  - Hippocampus/drug effects/physiopathology
MH  - Male
MH  - NF-kappa B/metabolism
MH  - Neoplasm Proteins/metabolism
MH  - Neurons/physiology
MH  - Neuroprotective Agents/*pharmacology
MH  - Nucleocytoplasmic Transport Proteins/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
MH  - Subarachnoid Hemorrhage/*complications/drug therapy/mortality/physiopathology
OTO - NOTNLM
OT  - apoptosis
OT  - ceftriaxone
OT  - early brain injury
OT  - excitatory amino acid transporter 2
OT  - subarachnoid hemorrhage
EDAT- 2014/03/19 06:00
MHDA- 2014/12/17 06:00
CRDT- 2014/03/18 06:00
PHST- 2013/11/07 00:00 [received]
PHST- 2014/02/25 00:00 [revised]
PHST- 2014/02/26 00:00 [accepted]
PHST- 2014/03/18 06:00 [entrez]
PHST- 2014/03/19 06:00 [pubmed]
PHST- 2014/12/17 06:00 [medline]
AID - S0306-4522(14)00207-3 [pii]
AID - 10.1016/j.neuroscience.2014.02.053 [doi]
PST - ppublish
SO  - Neuroscience. 2014 May 30;268:21-32. doi: 10.1016/j.neuroscience.2014.02.053. 
      Epub 2014 Mar 12.