scholarly journals The Upregulation of Glial Glutamate Transporter-1 Participates in the Induction of Brain Ischemic Tolerance in Rats

2007 ◽  
Vol 27 (7) ◽  
pp. 1352-1368 ◽  
Author(s):  
Min Zhang ◽  
Wen-Bin Li ◽  
Jin-Xia Geng ◽  
Qing-Jun Li ◽  
Xiao-Cai Sun ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Pyramidal Neurons ◽  
Glutamate Transporter ◽  
Protective Role ◽  
Ischemic Tolerance ◽  
Delayed Neuronal Death ◽  
Ischemic Insult ◽  
Glial Glutamate Transporter ◽  
Glutamate Transporter 1

Glial glutamate transporter-1 (GLT-1) plays an essential role in removing glutamate from the extracellular space and maintaining the glutamate below neurotoxic level in the brain. To explore whether GLT-1 plays a role in the acquisition of brain ischemic tolerance (BIT) induced by cerebral ischemic preconditioning (CIP), the present study was undertaken to observe in vivo changes in the expression of GLT-1 and glial fibrillary acidic protein (GFAP) in the CA1 hippocampus during the induction of BIT, and the effect of dihydrokainate (DHK), an inhibitor of GLT-1, on the acquisition of BIT in rats. Immunohistochemistry for GFAP showed that the processes of astrocytes were prolonged after a CIP 2 days before the lethal ischemic insult, which could protect pyramidal neurons in the CA1 hippocampus against delayed neuronal death induced normally by lethal ischemic insult. The prolonged processes extended into the area between the pyramidal neurons and tightly surrounded them. These changes made the pyramidal layer look like a ‘shape grid’. Simultaneously, the prolonged and extended processes showed a great deal of GLT-1. Western blotting analysis showed significant upregulation of GLT-1 expression after the CIP, especially when it was administered 2 days before the subsequent lethal ischemic insult. Neuropathological evaluation by thionin staining showed that DHK dose-dependently blocked the protective role of CIP against delayed neuronal death induced normally by lethal brain ischemia. It might be concluded that the surrounding of pyramidal neurons by astrocytes and upregulation of GLT-1 induced by CIP played an important role in the acquisition of the BIT induced by CIP.

scholarly journals Activation of p38 MAPK participates in the sulbactam-induced cerebral ischemic tolerance mediated by glial glutamate transporter-1 upregulation in rats

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiao-Hui Xian ◽  
Jun-Xia Gao ◽  
Jie Qi ◽  
Shu-Juan Fan ◽  
Min Zhang ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Hippocampal Neurons ◽  
Time Course ◽  
Glutamate Transporter ◽  
Global Cerebral Ischemia ◽  
Ischemic Insult ◽  
Glial Glutamate Transporter ◽  
Cerebral Ischemic ◽  
Glutamate Transporter 1

AbstractOur previous studies have shown that sulbactam can play a neuroprotection role in hippocampal neurons by upregulating the expression and function of glial glutamate transporter-1 (GLT-1) during ischemic insult. Here, using rat global cerebral ischemia model, we studied in vivo the role of p38 mitogen-activated protein kinases (MAPK) in the sulbactam-induced GLT-1 upregulation and neuroprotection against ischemia. The hippocampal CA1 field was selected as observing target. The expressions of phosphorylated-p38 MAPK and GLT-1 were assayed with western blot analysis and immunohistochemistry. The condition of delayed neuronal death (DND) was assayed with neuropathological evaluation under thionin staining. It was shown that administration of sulbactam protected CA1 hippocampal neurons against ischemic insult accompanied with significantly upregulation in the expressions of phosphorylated-p38 MAPK and GLT-1. The time course analysis showed that sulbactam activated p38 MAPK before the GLT-1 upregulation in either normal or global cerebral ischemic rats. Furthermore, inhibiting p38 MAPK activation by SB203580 blocked the GLT-1 upregulation and neuroprotection induced by sulbactam. The above results suggested that p38 MAPK, at least partly, participated in the sulbactam-induced brain tolerance to ischemia mediated by GLT-1 upregulation in rats.

Delayed Neuronal Death and Ischemic Tolerance

1995 ◽  
pp. 19-28
Author(s):  
T. Kirino ◽  
T. Nakagomi ◽  
H. Kanemitsu ◽  
A. Tamura
Keyword(s):  
Neuronal Death ◽  
Ischemic Tolerance ◽  
Delayed Neuronal Death

Caffeine Releasable Stores of Ca2+ Show Depletion Prior to the Final Steps in Delayed CA1 Neuronal Death

2004 ◽  
Vol 92 (5) ◽  
pp. 2960-2967 ◽  
Author(s):  
Hong Xing ◽  
Aryan Azimi-Zonooz ◽  
C. William Shuttleworth ◽  
John A. Connor
Keyword(s):  
Endoplasmic Reticulum ◽  
Neuronal Death ◽  
Carotid Arteries ◽  
Cell Function ◽  
Mean Amplitude ◽  
Delayed Neuronal Death ◽  
Ischemic Insult ◽  
Cell Degeneration ◽  
Ca1 Neurons ◽  
The Mean

In addition to their role in signaling, Ca2+ ions in the endoplasmic reticulum also regulate important steps in protein processing and trafficking that are critical for normal cell function. Chronic depletion of Ca2+ in the endoplasmic reticulum has been shown to lead to cell degeneration and has been proposed as a mechanism underlying delayed neuronal death following ischemic insults to the CNS. Experiments here have assessed the relative content of ryanodine receptor-gated stores in CA1 neurons by measuring cytoplasmic Ca2+ increases induced by caffeine. These measurements were performed on CA1 neurons, in slice, from normal gerbils, and compared with responses from this same population of neurons 54–60 h after animals had undergone a standard ischemic insult: 5-min bilateral occlusion of the carotid arteries. The mean amplitude of responses in the postischemic population were less than one-third of those in control or sham-operated animals, and 35% of the neurons from postischemic animals showed very small responses that were ∼10% of the control population mean. Refilling of these stores after caffeine challenges was also impaired in postischemic neurons. These observations are consistent with our earlier finding that voltage-gated influx is sharply reduced in postischemic in CA1 neurons and the hypothesis that the resulting depletion in endosomal Ca2+ is an important cause of delayed neuronal death.

scholarly journals Genome-Wide Gene Expression Analysis for Induced Ischemic Tolerance and Delayed Neuronal Death following Transient Global Ischemia in Rats

2004 ◽  
Vol 24 (2) ◽  
pp. 212-233 ◽  
Author(s):  
Nobutaka Kawahara ◽  
Yan Wang ◽  
Akitake Mukasa ◽  
Kazuhide Furuya ◽  
Tatsuya Shimizu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Neuronal Death ◽  
Gene Expression Analysis ◽  
Ischemic Tolerance ◽  
Global Ischemia ◽  
Delayed Neuronal Death ◽  
Regulation Of Transcription ◽  
Genome Wide ◽  
A Genome

enome-wide gene expression analysis of the hippocampal CA1 region was conducted in a rat global ischemia model for delayed neuronal death and induced ischemic tolerance using an oligonucleotide-based DNA microarray containing 8,799 probes. The results showed that expression levels of 246 transcripts were increased and 213 were decreased following ischemia, corresponding to 5.1% of the represented probe sets. These changes were divided into seven expression clusters using hierarchical cluster analysis, each with distinct conditions and time-specific patterns. Ischemic tolerance was associated with transient up-regulation of transcription factors (c-Fos, JunB Egr-1, −2, −4, NGFI-B), Hsp70 and MAP kinase cascade-related genes (MKP-1), which are implicated cell survival. Delayed neuronal death exhibited complex long-lasting changes of expression, such as up-regulation of proapoptotic genes (GADD153, Smad2, Dral, Caspase-2 and −3) and down-regulation of genes implicated in survival signaling (MKK2, and PI4 kinase, DAG/PKC signaling pathways), suggesting an imbalance between death and survival signals. Our study provides a differential gene expression profile between delayed neuronal death and induced ischemic tolerance in a genome-wide analysis, and contributes to further understanding of the complex molecular pathophysiology in cerebral ischemia.

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