title: Gray Matter Hypoxia in the Brain of the Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis.
abstract: BACKGROUND
  Multiple sclerosis (MS) has a significant inflammatory component and may have significant gray matter (GM) pathophysiology. Brain oxygenation is a sensitive measurement of the balance between metabolic need and oxygen delivery. There is evidence that inflammation and hypoxia are interdependent. In this paper, we applied novel, implanted PO2 sensors to measure hypoxia in cortical and cerebellar GM, in an inflammation-induced mouse model of MS.
  
  
  OBJECTIVE
  Quantify oxygenation in cortical and cerebellar GM in the awake, unrestrained experimental autoimmune encephalomyelitis (EAE) mouse model and to relate the results to symptom level and disease time-course.
  
  
  METHODS
  C57BL/6 mice were implanted with a fiber-optic sensor in the cerebellum (n = 13) and cortex (n = 24). Animals were induced with stimulation of the immune response and sensitization to myelin oligodendrocyte glycoprotein (MOG). Controls did not have MOG. We measured PO2 in awake, unrestrained animals from pre-induction (baseline) up to 36 days post-induction for EAE and controls.
  
  
  RESULTS
  There were more days with hypoxia than hyperoxia (cerebellum: 34/67 vs. 18/67 days; cortex: 85/112 vs. 22/112) compared to time-matched controls. The average decline in PO2 on days that were significantly lower than time-matched controls was -8.8±6.0 mmHg (mean ± SD) for the cerebellum and -8.0±4.6 for the cortex. Conversely, the average increase in PO2 on days that were significantly hyperoxic was +3.2±2.8 mmHg (mean ± SD) for the cerebellum and +0.8±2.1 for the cortex. Cortical hypoxia related to increased behavioral deficits. Evidence for hypoxia occurred before measurable behavioral deficits.
  
  
  CONCLUSIONS
  A highly inflammatory condition primed to a white matter (WM) autoimmune response correlates with significant hypoxia and increased variation in oxygenation in GM of both cerebellum and cortex in the mouse EAE model of MS.
authors.affiliation: Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Johnson
authors.affiliation: Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Nabeela
authors.initials: N
authors.lastname: Nathoo
authors.affiliation: Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: James A
authors.initials: JA
authors.lastname: Rogers
authors.affiliation: Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Wee Yong
authors.affiliation: Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jeff F
authors.initials: JF
authors.lastname: Dunn
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism*; D005260:Female; D066128:Gray Matter / Q000378:metabolism* / Q000473:pathology; D000860:Hypoxia / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010101:Oxygen Consumption; D013997:Time Factors