title: Effect of N-methyl-D-aspartate and inhibition of neuronal nitric oxide on collateral cerebral blood flow after middle cerebral artery occlusion.
abstract: OBJECTIVE
  To study the role of N-methyl-D-aspartate (NMDA) receptor activation and selective inhibition of neuronal nitric oxide synthase with 7-nitroindazole (7-NI) on blood flow to collateral-dependent tissue (CDT) after middle cerebral artery (MCA) occlusion.
  
  
  METHODS
  A left craniotomy was performed in each of 11 dogs with the animals under halothane anesthesia. A branch of the MCA was occluded and cannulated distally for determination of CDT, using a "shadow flow" technique. Cerebral blood flow (CBF) and vascular pressures were measured and used to calculate vascular resistance.
  
  
  METHODS
  Our shadow flow model has the ability to identify an area of CDT, with minimal contamination from overlap flow within a morphologically identified "risk area" for MCA branch occlusion.
  
  
  RESULTS
  NMDA increased blood flow to CDT by 56.2%, while normal ipsilateral and contralateral cerebrum increased by at least 35% from baseline. 7-NI caused a significant drop in regional CBF, with the greatest drop of 41.7% occurring in the CDT. Normal ipsilateral and contralateral CBF was reduced by 31.7 and 23.9%, respectively. The dilator response to NMDA was significantly attenuated after 7-NI administration, except in CDT where flow increased ("inverse steal"). Cerebral vascular resistance decreased in response to NMDA and increased with 7-NI.
  
  
  CONCLUSIONS
  Neuronal nitric oxide production seems to play an important role in regulating vascular tone and CBF to CDT after MCA occlusion. Selective preservation of blood flow to CDT seems to be mediated by NMDA receptor activation but independent of neuronal nitric oxide production.
authors.affiliation: Division of Neurosurgery, University of Iowa College of Medicine, Iowa City, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Robertson
authors.forename: C M
authors.initials: CM
authors.lastname: Loftus
mesh_terms: D000818:Animals; D001157:Arterial Occlusive Diseases / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D002561:Cerebrovascular Disorders / Q000503:physiopathology*; D003097:Collateral Circulation / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007191:Indazoles / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D007191:Indazoles; D009569:Nitric Oxide; D016202:N-Methylaspartate; C080122:7-nitroindazole