Abstract | BACKGROUND AND PURPOSE: METHODS: CTX (200 mg/kg per day, IP) was administered for 5 consecutive days before transient focal ischemia, which was induced by intraluminal thread occlusion of the middle cerebral artery for 90 minutes or permanently. RESULTS: Repeated CTX injections enhanced GLT-1 mRNA and protein expressions after 3 and 5 days of treatment, respectively. CTX-pretreated animals showed a reduction in infarct volume by 58% (reperfusion) and 39% (permanent), compared with the vehicle-pretreated animals at 24 hours postischemia (P<0.01). Lower doses of CTX (20 mg/kg per day and 100 mg/kg per day) reduced infarct volumes to a lesser degree. The injection of GLT-1 inhibitor ( dihydrokainate) at 30 minutes before ischemia ameliorated the effect of CTX pretreatment. However, CTX administration at 30 minutes after ischemia produced no significant reduction in infarct volume. CTX reduced the levels of proinflammatory cytokines ( tumor necrosis factor-alpha, FasL), matrix metalloproteinase (MMP)-9, and activated caspase-9 (P<0.01). In addition, CTX-pretreated animals showed better functional recovery at day 1 to week 5 after ischemia (P<0.05). CONCLUSIONS: This study presents evidence that CTX induces ischemic tolerance in focal cerebral ischemia and that this is mediated by GLT-1 upregulation.
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Authors | Kon Chu, Soon-Tae Lee, Dong-In Sinn, Song-Yi Ko, Eun-Hee Kim, Jeong-Min Kim, Se-Jeong Kim, Dong-Kyu Park, Keun-Hwa Jung, Eun-Cheol Song, Sang Kun Lee, Manho Kim, Jae-Kyu Roh |
Journal | Stroke
(Stroke)
Vol. 38
Issue 1
Pg. 177-82
(Jan 2007)
ISSN: 1524-4628 [Electronic] United States |
PMID | 17122424
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Bacterial Agents
- Excitatory Amino Acid Transporter 2
- Neuroprotective Agents
- Neurotoxins
- RNA, Messenger
- Glutamic Acid
- Ceftriaxone
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Topics |
- Animals
- Anti-Bacterial Agents
(pharmacology)
- Astrocytes
(drug effects, metabolism)
- Brain
(blood supply, drug effects, physiopathology)
- Brain Ischemia
(drug therapy, metabolism, physiopathology)
- Ceftriaxone
(pharmacology)
- Cell Communication
(drug effects, physiology)
- Cytoprotection
(drug effects, physiology)
- Disease Models, Animal
- Excitatory Amino Acid Transporter 2
(drug effects, genetics, metabolism)
- Glutamic Acid
(metabolism)
- Male
- Neurons
(metabolism)
- Neuroprotective Agents
(pharmacology)
- Neurotoxins
(antagonists & inhibitors, metabolism)
- RNA, Messenger
(drug effects, metabolism)
- Rats
- Rats, Sprague-Dawley
- Treatment Outcome
- Up-Regulation
(drug effects, physiology)
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