title: Brain tissue sodium is a ticking clock telling time after arterial occlusion in rat focal cerebral ischemia.
abstract: OBJECTIVE
  Many patients with acute stroke are excluded from receiving thrombolysis agents within the necessary time limit (3 or 6 hours from stroke onset) because they or their family members are unable provide the time of stroke onset. Brain tissue sodium concentration ([Na(+)]) increases gradually and incessantly during the initial hours of experimental focal cerebral ischemia but only in severely damaged brain regions. We propose that this steady increase in [Na(+)] can be used to estimate the time after arterial occlusion in the rat middle cerebral artery occlusion model of ischemic stroke.
  
  
  METHODS
  Sixteen anesthetized Sprague-Dawley rats underwent permanent middle cerebral artery occlusion combined with bilateral common artery occlusion. After 100 to 450 minutes, diffusion-weighted MRI was used to generate apparent diffusion coefficient (ADC) maps, cerebral blood flow (CBF) was determined with (14)C-iodoantipyrine (in a subset of 7 animals), and the brain was frozen. Autoradiographic CBF sections and punch samples for Na(+) analysis were obtained from the brain at the same level of the MR image. Severely at risk regions were identified with an ADC of <520 microm(2)/s and, in the subset, with both ADC of <520 microm(2)/s and CBF of <40 mL. 100 g(-1). min(-1).
  
  
  RESULTS
  Both CBF and the ADC dropped quickly and remained stable in the initial hours after ischemic onset. Linear regression revealed strong linearity between [Na(+)] and time after onset, with a slope of 0.95 or 1.00 (mEq/kg DW)/min, with both ADC and ADC-plus-CBF criteria, respectively. The 95% CIs at 180 and 360 minutes were between 41 and 52 minutes.
  
  
  CONCLUSIONS
  The time after ischemic onset can be estimated with this 2-step process. First, ADC and CBF are used to identify severely endangered regions. Second, the [Na(+)] in these regions is used to estimate time after onset. The favorable 95% CIs at the time limits for thrombolytic therapy and the availability of measurements of ADC, CBF, and [Na(+)] in humans through the use of MRI suggest that this time-estimation scheme could be used to assess the appropriateness of thrombolysis for patients who do not know when the stroke occurred.
authors.affiliation: Department of Anesthesiology, Allegheny General Hospital, Pittsburgh, PA 15212-4772, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: W
authors.initials: W
authors.lastname: Hu
authors.forename: A D
authors.initials: AD
authors.lastname: Perez-Trepichio
authors.forename: T C
authors.initials: TC
authors.lastname: Ng
authors.forename: A J
authors.initials: AJ
authors.lastname: Furlan
authors.forename: A W
authors.initials: AW
authors.lastname: Majors
authors.forename: S C
authors.initials: SC
authors.lastname: Jones
mesh_terms: D000818:Animals; D001683:Biological Clocks; D015415:Biomarkers; D001923:Brain Chemistry; D002545:Brain Ischemia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D017536:Carotid Artery, Common; D016893:Carotid Stenosis / Q000150:complications / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D004058:Diffusion; D004334:Drug Administration Schedule; D007091:Image Processing, Computer-Assisted; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D015912:Thrombolytic Therapy; D013997:Time Factors
chemical_list: D015415:Biomarkers; D012964:Sodium