title: Malignant infarction of the middle cerebral artery in a porcine model. A pilot study.
abstract: OBJECTIVE
  Interspecies variability and poor clinical translation from rodent studies indicate that large gyrencephalic animal stroke models are urgently needed. We present a proof-of-principle study describing an alternative animal model of malignant infarction of the middle cerebral artery (MCA) in the common pig and illustrate some of its potential applications. We report on metabolic patterns, ionic profile, brain partial pressure of oxygen (PtiO2), expression of sulfonylurea receptor 1 (SUR1), and the transient receptor potential melastatin 4 (TRPM4).
  
  
  METHODS
  A 5-hour ischemic infarct of the MCA territory was performed in 5 2.5-to-3-month-old female hybrid pigs (Large White x Landrace) using a frontotemporal approach. The core and penumbra areas were intraoperatively monitored to determine the metabolic and ionic profiles. To determine the infarct volume, 2,3,5-triphenyltetrazolium chloride staining and immunohistochemistry analysis was performed to determine SUR1 and TRPM4 expression.
  
  
  RESULTS
  PtiO2 monitoring showed an abrupt reduction in values close to 0 mmHg after MCA occlusion in the core area. Hourly cerebral microdialysis showed that the infarcted tissue was characterized by reduced concentrations of glucose (0.03 mM) and pyruvate (0.003 mM) and increases in lactate levels (8.87mM), lactate-pyruvate ratio (4202), glycerol levels (588 μM), and potassium concentration (27.9 mmol/L). Immunohistochemical analysis showed increased expression of SUR1-TRPM4 channels.
  
  
  CONCLUSIONS
  The aim of the present proof-of-principle study was to document the feasibility of a large animal model of malignant MCA infarction by performing transcranial occlusion of the MCA in the common pig, as an alternative to lisencephalic animals. This model may be useful for detailed studies of cerebral ischemia mechanisms and the development of neuroprotective strategies.
authors.affiliation: Department of Neurosurgery, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.|Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Fuat
authors.identifier: http://orcid.org/0000-0002-9459-0915
authors.initials: F
authors.lastname: Arikan
authors.affiliation: Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Tamara
authors.initials: T
authors.lastname: Martínez-Valverde
authors.affiliation: Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Ángela
authors.initials: Á
authors.lastname: Sánchez-Guerrero
authors.affiliation: Experimental Surgery Unit, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Campos
authors.affiliation: Experimental Surgery Unit, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Marielle
authors.initials: M
authors.lastname: Esteves
authors.affiliation: Department of Neurosurgery, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Dario
authors.initials: D
authors.lastname: Gandara
authors.affiliation: Department of Neurosurgery, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.|Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Torné
authors.affiliation: Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Lidia
authors.initials: L
authors.lastname: Castro
authors.affiliation: IRTA, Animal Breeding and Genetics Program, Monells, Girona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Dalmau
authors.affiliation: IRTA, Animal Breeding and Genetics Program, Monells, Girona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Tibau
authors.affiliation: Department of Neurosurgery, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.|Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Sahuquillo
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019344:Lactic Acid / Q000378:metabolism; D020768:Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology*; D010092:Oximetry; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D011188:Potassium / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism; D064233:Sulfonylurea Receptors / Q000235:genetics / Q000378:metabolism; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism
chemical_list: D064233:Sulfonylurea Receptors; D050053:TRPM Cation Channels; D019344:Lactic Acid; D019289:Pyruvic Acid; D005947:Glucose; D005990:Glycerol; D011188:Potassium; D010100:Oxygen