title: MRI evidence that glibenclamide reduces acute lesion expansion in a rat model of spinal cord injury.
abstract: METHODS
  Experimental, controlled, animal study.
  
  
  OBJECTIVE
  To use non-invasive magnetic resonance imaging (MRI) to corroborate invasive studies showing progressive expansion of a hemorrhagic lesion during the early hours after spinal cord trauma and to assess the effect of glibenclamide, which blocks Sur1-Trpm4 channels implicated in post-traumatic capillary fragmentation, on lesion expansion.
  
  
  METHODS
  Baltimore.
  
  
  METHODS
  Adult female Long-Evans rats underwent unilateral impact trauma to the spinal cord at C7, which produced ipsilateral but not contralateral primary hemorrhage. In series 1 (six control rats and six administered glibenclamide), hemorrhagic lesion expansion was characterized using MRI at 1 and 24 h after trauma. In series 2, hemorrhagic lesion size was characterized on coronal tissue sections at 15 min (eight rats) and at 24 h after trauma (eight control rats and eight administered glibenclamide).
  
  
  RESULTS
  MRI (T2 hypodensity) showed that lesions expanded 2.3±0.33-fold (P<0.001) during the first 24 h in control rats, but only 1.2±0.07-fold (P>0.05) in glibenclamide-treated rats. Measuring the areas of hemorrhagic contusion on tissue sections at the epicenter showed that lesions expanded 2.2±0.12-fold (P<0.001) during the first 24 h in control rats, but only 1.1±0.05-fold (P>0.05) in glibenclamide-treated rats. Glibenclamide treatment was associated with significantly better neurological function (unilateral BBB scores) at 24 h in both the ipsilateral (median scores, 9 vs 0; P<0.001) and contralateral (median scores, 12 vs 2; P<0.001) hindlimbs.
  
  
  CONCLUSIONS
  MRI is an accurate non-invasive imaging biomarker of lesion expansion and is a sensitive measure of the ability of glibenclamide to reduce lesion expansion.
authors.affiliation: 1] Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA [2] Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA [3] Department of Physiology, University of Maryland School of Medicine, Baltimore MD, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Simard
authors.forename: P G
authors.initials: PG
authors.lastname: Popovich
authors.forename: O
authors.initials: O
authors.lastname: Tsymbalyuk
authors.forename: J
authors.initials: J
authors.lastname: Caridi
authors.forename: R P
authors.initials: RP
authors.lastname: Gullapalli
authors.forename: M J
authors.initials: MJ
authors.lastname: Kilbourne
authors.forename: V
authors.initials: V
authors.lastname: Gerzanich
mesh_terms: D000375:Aging; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005905:Glyburide / Q000627:therapeutic use*; D006470:Hemorrhage / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D051381:Rats; D020318:Rats, Long-Evans; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D005905:Glyburide
references.citation: Magn Reson Med. 2000 Apr;43(4):594-600
references.pmid: 10748436
references.citation: Sci Transl Med. 2010 Apr 21;2(28):28ra29
references.pmid: 20410530
references.citation: J Neurotrauma. 2013 Mar 15;30(6):441-52
references.pmid: 23517137
references.citation: J Neurotrauma. 2014 Feb 1;31(3):239-55
references.pmid: 23859435
references.citation: Exp Neurol. 2012 Jan;233(1):566-74
references.pmid: 22177998
references.citation: Lab Invest. 1978 Sep;39(3):236-53
references.pmid: 713489
references.citation: J Neurosurg Spine. 2012 Sep;17(1 Suppl):157-229
references.pmid: 22985382
references.citation: Nat Med. 2009 Feb;15(2):185-91
references.pmid: 19169264
references.citation: Spinal Cord. 1999 Aug;37(8):580-4
references.pmid: 10455535
references.citation: Exp Neurol. 1999 May;157(1):19-42
references.pmid: 10222106
references.citation: Ann N Y Acad Sci. 1999;890:366-84
references.pmid: 10668443
references.citation: Spine (Phila Pa 1976). 1990 Jul;15(7):630-8
references.pmid: 2218708
references.citation: Exp Neurol. 2012 Feb;233(2):829-35
references.pmid: 22197047
references.citation: Nat Med. 2006 Apr;12(4):433-40
references.pmid: 16550187
references.citation: AAPS PharmSciTech. 2009;10(3):928-34
references.pmid: 19629706
references.citation: J Neurosurg Spine. 2012 Sep;17(3):243-50
references.pmid: 22794535
references.citation: Exp Neurol. 2012 Feb;233(2):615-22
references.pmid: 21145891
references.citation: Transl Stroke Res. 2012 Jun;3(2):286-95
references.pmid: 22707989
references.citation: J Neurotrauma. 1995 Feb;12(1):1-21
references.pmid: 7783230
references.citation: Brain Sci. 2013 Mar 7;3(1):215-38
references.pmid: 23667741
references.citation: Stroke. 2009 Feb;40(2):604-9
references.pmid: 19023097
references.citation: J Comput Assist Tomogr. 1994 May-Jun;18(3):357-62
references.pmid: 8188899
references.citation: No Shinkei Geka. 1993 Jan;21(1):45-51
references.pmid: 8426687
references.citation: Spinal Cord. 2006 Sep;44(9):523-9
references.pmid: 16389270
references.citation: Acta Neurochir Suppl. 1999;73:103-10
references.pmid: 10494351
references.citation: J Clin Invest. 2007 Aug;117(8):2105-13
references.pmid: 17657312
references.citation: J Biol Chem. 2013 Feb 1;288(5):3655-67
references.pmid: 23255597
references.citation: Behav Brain Res. 2001 Feb 15;119(1):1-13
references.pmid: 11164520