Abstract | BACKGROUND AND PURPOSE: METHODS: To induce focal ischemia, the middle cerebral artery (MCA) was occluded by using the intraluminal thread technique (tMCAO). 1400W was administered, after tMCAO, by using an Alzet osmotic pump to yield a drug delivery rate of 2.5 mg/kg/h. Results. Postischemic treatment with 1400W induced a reduction in the neurofunctional impairment and in the total volume of brain infarct. Western blot analysis showed ischemia-induced expression of iNOS. Treatment with 1400W partially prevented delayed ATP reduction and produced inhibition of the subsequent delayed increase in glutamate levels caused by the ischemic insult. CONCLUSIONS: Our data indicate that 1400W improves stroke outcome, an effect concomitant to the inhibition of both ischemia-induced decrease in brain ATP levels and increase in glutamate release. These results provide evidence indicating that the expression of iNOS induced by ischemia may contribute to the progression of the ischemic infarct and have important therapeutic implications for the management of stroke.
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Authors | Fernando J Pérez-Asensio, Olivia Hurtado, María C Burguete, María A Moro, Juan B Salom, Ignacio Lizasoain, Germán Torregrosa, Juan C Leza, Enrique Alborch, José Castillo, Richard G Knowles, Pedro Lorenzo |
Journal | Neurobiology of disease
(Neurobiol Dis)
Vol. 18
Issue 2
Pg. 375-84
(Mar 2005)
ISSN: 0969-9961 [Print] United States |
PMID | 15686966
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amidines
- Amino Acid Transport System X-AG
- Benzylamines
- Enzyme Inhibitors
- N-(3-(aminomethyl)benzyl)acetamidine
- Neuroprotective Agents
- Nitric Oxide
- Glutamic Acid
- Adenosine Triphosphate
- Nitric Oxide Synthase
- Nitric Oxide Synthase Type II
- Nos2 protein, rat
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Topics |
- Adenosine Triphosphate
(metabolism)
- Amidines
(pharmacology, therapeutic use)
- Amino Acid Transport System X-AG
(metabolism)
- Animals
- Benzylamines
(pharmacology, therapeutic use)
- Brain
(drug effects, metabolism, physiopathology)
- Cerebral Infarction
(drug therapy, metabolism, physiopathology)
- Cytoprotection
(drug effects, physiology)
- Disease Models, Animal
- Down-Regulation
(drug effects, physiology)
- Enzyme Inhibitors
(pharmacology)
- Glutamic Acid
(metabolism)
- Infarction, Middle Cerebral Artery
(drug therapy, metabolism, physiopathology)
- Ischemic Attack, Transient
(drug therapy, metabolism, physiopathology)
- Male
- Neuroprotective Agents
(pharmacology)
- Nitric Oxide
(biosynthesis)
- Nitric Oxide Synthase
(antagonists & inhibitors, metabolism)
- Nitric Oxide Synthase Type II
- Rats
- Rats, Wistar
- Stroke
(drug therapy, metabolism, physiopathology)
- Treatment Outcome
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