title: Thrombotic stroke in the anesthetized monkey (Macaca mulatta): characterization by MRI--a pilot study.
abstract: BACKGROUND
  The lack of a relevant stroke model in large nonhuman primates hinders the development of innovative diagnostic/therapeutic approaches concerned with this cerebrovascular disease. Our objective was to develop a novel and clinically relevant model of embolic stroke in the anesthetized monkey that incorporates readily available clinical imaging techniques and that would allow the possibility of drug delivery including strategies of reperfusion.
  
  
  METHODS
  Thrombin was injected into the lumen of the middle cerebral artery (MCA) in 12 anesthetized (sevoflurane) male rhesus macaques (Macaca mulatta). Sequential MRI studies (including angiography, FLAIR, PWI, DWI, and gadolinium-enhanced T1W imaging) were performed in a 3T clinical MRI. Physiological and biochemical parameters were monitored throughout the investigations.
  
  
  RESULTS
  Once standardized, the surgical procedure induced transient occlusion of the middle cerebral artery in all operated animals. All animals studied showed spontaneous reperfusion, which occurred some time between 2 h and 7 days post-ictus. Eighty percent of the studied animals showed diffusion/perfusion mismatch. The ischemic lesions at 24 h spared both superficial and profound territories of the MCA. Some animals presented hemorrhagic transformation at 7 days post-ictus.
  
  
  CONCLUSIONS
  In this study, we developed a pre-clinically relevant model of embolic stroke in the anesthetized nonhuman primate.
authors.affiliation: INSERM U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, GIP Cyceron, Université de Caen-Basse Normandie, Caen, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Gauberti
authors.forename: Pauline
authors.initials: P
authors.lastname: Obiang
authors.forename: Pierre
authors.initials: P
authors.lastname: Guedin
authors.forename: Anne
authors.initials: A
authors.lastname: Balossier
authors.forename: Clément
authors.initials: C
authors.lastname: Gakuba
authors.forename: Anne Sophie
authors.initials: AS
authors.lastname: Diependaele
authors.forename: Laurent
authors.initials: L
authors.lastname: Chazalviel
authors.forename: Denis
authors.initials: D
authors.lastname: Vivien
authors.forename: Alan R
authors.initials: AR
authors.lastname: Young
authors.forename: Véronique
authors.initials: V
authors.lastname: Agin
authors.forename: Cyrille
authors.initials: C
authors.lastname: Orset
mesh_terms: D000758:Anesthesia; D000778:Anesthetics, Dissociative; D018685:Anesthetics, Inhalation; D000818:Animals; D001279:Atracurium; D003399:Craniotomy; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D004195:Disease Models, Animal; D007091:Image Processing, Computer-Assisted; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology; D007649:Ketamine; D008253:Macaca mulatta; D018810:Magnetic Resonance Angiography / Q000379:methods; D008279:Magnetic Resonance Imaging; D008297:Male; D008738:Methyl Ethers; D009460:Neurologic Examination; D003473:Neuromuscular Nondepolarizing Agents; D009609:Nitrous Oxide; D010865:Pilot Projects; D015203:Reproducibility of Results; D000077149:Sevoflurane; D020521:Stroke / Q000209:etiology* / Q000473:pathology*; D013923:Thromboembolism / Q000150:complications* / Q000473:pathology*
chemical_list: D000778:Anesthetics, Dissociative; D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D003473:Neuromuscular Nondepolarizing Agents; D001279:Atracurium; D000077149:Sevoflurane; D007649:Ketamine; D009609:Nitrous Oxide