Transient focal ischemia produced by local infusion of endothelin-1 (ET1) in the territory of the middle cerebral artery has been proposed as a potentially useful model for the screening of drugs developed for the treatment of thrombo-embolic stroke. However, most of the data rely exclusively on the assessment of the infarct volume, which is only a partial predictor of the neurological outcome of stroke. Here, we have validated the model using a multimodal approach for the assessment of neuroprotection, which includes (i) determination of the infarct volume by 2,3,5-triphenyltetrazolium chloride staining; (ii) an in-depth behavioral analysis of the neurological deficit; and (iii) an EEG analysis of electrophysiological abnormalities in the peri-infarct somatosensory forelimb cortical area, S1FL. The noncompetitive NMDA receptor antagonist, MK-801 (3 mg/kg, injected i.p. 20 min after ET1 infusion in conscious rats) could reduce the infarct volume, reverse the EEG changes occurring at early times post-ET1, and markedly improve the neurological deficit in ischemic animals. The latter effect, however, was visible at day 3 post-ET1, because the drug itself produced substantial behavioral abnormalities at earlier times. We conclude that a multimodal approach can be applied to the ET1 model of focal ischemia, and that MK-801 can be used as a reference compound to which the activity of safer neuroprotective drugs should be compared. (c) 2007 Elsevier B.V. All rights reserved.

Multimodal assessment of neuroprotection applied to the use of MK-801 in the endothelin-1 model of transient focal brain ischemia / Slavianka Georgieva, Moyanova; Lidia Vasileva, Kortenska; Rumiana Gesheva, Mitreva; Vyara Dincova, Pashova; Richard Teke, Ngomba; Nicoletti, Ferdinando. - In: BRAIN RESEARCH. - ISSN 0006-8993. - 1153:1(2007), pp. 58-67. [10.1016/j.brainres.2007.03.070]

Multimodal assessment of neuroprotection applied to the use of MK-801 in the endothelin-1 model of transient focal brain ischemia

NICOLETTI, Ferdinando
2007

Abstract

Transient focal ischemia produced by local infusion of endothelin-1 (ET1) in the territory of the middle cerebral artery has been proposed as a potentially useful model for the screening of drugs developed for the treatment of thrombo-embolic stroke. However, most of the data rely exclusively on the assessment of the infarct volume, which is only a partial predictor of the neurological outcome of stroke. Here, we have validated the model using a multimodal approach for the assessment of neuroprotection, which includes (i) determination of the infarct volume by 2,3,5-triphenyltetrazolium chloride staining; (ii) an in-depth behavioral analysis of the neurological deficit; and (iii) an EEG analysis of electrophysiological abnormalities in the peri-infarct somatosensory forelimb cortical area, S1FL. The noncompetitive NMDA receptor antagonist, MK-801 (3 mg/kg, injected i.p. 20 min after ET1 infusion in conscious rats) could reduce the infarct volume, reverse the EEG changes occurring at early times post-ET1, and markedly improve the neurological deficit in ischemic animals. The latter effect, however, was visible at day 3 post-ET1, because the drug itself produced substantial behavioral abnormalities at earlier times. We conclude that a multimodal approach can be applied to the ET1 model of focal ischemia, and that MK-801 can be used as a reference compound to which the activity of safer neuroprotective drugs should be compared. (c) 2007 Elsevier B.V. All rights reserved.
2007
electrophysiological outcome; endothelin-1 model of ischemia; mk-801; neurological deficit; neuroprotection
01 Pubblicazione su rivista::01a Articolo in rivista
Multimodal assessment of neuroprotection applied to the use of MK-801 in the endothelin-1 model of transient focal brain ischemia / Slavianka Georgieva, Moyanova; Lidia Vasileva, Kortenska; Rumiana Gesheva, Mitreva; Vyara Dincova, Pashova; Richard Teke, Ngomba; Nicoletti, Ferdinando. - In: BRAIN RESEARCH. - ISSN 0006-8993. - 1153:1(2007), pp. 58-67. [10.1016/j.brainres.2007.03.070]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/17938
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