Document Detail

Pre- and postischemic effects of the NMDA receptor antagonist dizocilpine maleate (MK-801) on collateral cerebral blood flow.
MedLine Citation:
PMID:  9384406     Owner:  NLM     Status:  MEDLINE    
The authors studied the effects of pre- and postischemic administration of dizocilpine maleate (MK-801) on collateral and regional cerebral blood flow (CBF). The ischemic penumbra appears to benefit most from the neuroprotective effects of MK-801. The precise mechanism by which MK-801 provides this neuroprotection remains controversial. Alterations in CBF have been demonstrated with MK-801 administration, but whether the response is an increase or decrease in flow has remained unclear. A left-sided craniectomy was performed in 20 dogs. A branch of the middle cerebral artery (MCA) was cannulated and collateral blood supply-dependent tissue (CDT) was identified using the "shadow flow" technique. Regional CBF was measured using radiolabeled microspheres. Six dogs received MK-801 (1 mg/kg administered intravenously) before they underwent MCA branch occlusion; the remaining 14 dogs received MK-801 after they underwent MCA occlusion. Cerebral blood flow and vascular pressures were measured 30 and 60 minutes after MK-801 administration. In animals that received MK-801 before MCA occlusion, CBF did not change significantly from baseline values before or after occlusion. In contrast, in animals that received MK-801 after MCA occlusion, CBF was significantly reduced in all regions of the brain, including the CDT. Collateral blood supply-dependent tissue showed a 51.7% reduction in flow, whereas normal CBF was reduced by 29.7%. The MK-801 induced cerebral vasoconstriction in both groups. The neuroprotective effects of MK-801 do not appear to be caused by the augmentation of collateral or global cerebral circulation and, in fact, may block the glutamate-mediated vasodilation that occurs during ischemia.
S C Robertson; N M Wetjen; B J Beer; C M Loftus
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of neurosurgery     Volume:  87     ISSN:  0022-3085     ISO Abbreviation:  J. Neurosurg.     Publication Date:  1997 Dec 
Date Detail:
Created Date:  1997-12-18     Completed Date:  1997-12-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0253357     Medline TA:  J Neurosurg     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  927-33     Citation Subset:  AIM; IM    
Division of Neurosurgery, University of Iowa College of Medicine, Iowa City 52242, USA.
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MeSH Terms
Blood Pressure / drug effects
Brain Ischemia / drug therapy*,  physiopathology,  radionuclide imaging
Cerebral Arteries / drug effects
Cerebrovascular Circulation / drug effects*
Collateral Circulation / drug effects*
Dizocilpine Maleate / administration & dosage,  therapeutic use*
Excitatory Amino Acid Antagonists / administration & dosage,  therapeutic use*
Injections, Intravenous
Neuroprotective Agents / administration & dosage,  therapeutic use*
Radiopharmaceuticals / diagnostic use
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
Vascular Resistance / drug effects
Vasoconstrictor Agents / therapeutic use
Vasodilation / drug effects
Reg. No./Substance:
0/Excitatory Amino Acid Antagonists; 0/Neuroprotective Agents; 0/Radiopharmaceuticals; 0/Receptors, N-Methyl-D-Aspartate; 0/Vasoconstrictor Agents; 77086-22-7/Dizocilpine Maleate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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