Functional consequences of ethidium bromide demyelination of the mouse ventral spinal cord.
Ethidium bromide (EB) has been extensively used in the rat as a model of spinal cord demyelination. However, this lesion has not been addressed in the adult mouse, a model with unlimited genetic potential. Here we characterize behavioral function, inflammation, myelin status and axonal viability following bilateral injection of 0.20 mg/mL ethidium bromide or saline into the ventral white matter (VWM) of female C57Bl/6 mice. EB-induced VWM demyelination significantly reduced spared VWM and Basso Mouse Scale (BMS) scores persisting out to 2 months. Chronic hindlimb dysfunction was accompanied by a persistent inflammatory response (demonstrated by CD45(+) immunofluorescence) and axonal loss (demonstrated by NF-M immunofluorescence and electron microscopy; EM). These cellular responses differ from the rat where inflammation resolves by 3-4 weeks and axon loss is minimal following EB demyelination. As these data suggest that EB-injection in the mouse spinal cord is a non-remyelinating lesion, we sought to ask whether wheel running could promote recovery by enhancing plasticity of local lumbar circuitry independent of remyelination. This did not occur as BMS and Treadscan assessment revealed no significant effect of wheel running on recovery. However, this study defines the importance of descending ventral motor pathways to locomotor function in the mouse as VWM loss results in a chronic hindlimb deficit.
['Kuypers|Nicholas J|NJ|', 'James|Kurtis T|KT|', 'Enzmann|Gaby U|GU|', 'Magnuson|David S K|DS|', 'Whittemore|Scott R|SR|']
D000818:Animals D003711:Demyelinating Diseases D004195:Disease Models, Animal D004305:Dose-Response Relationship, Drug D004791:Enzyme Inhibitors D004996:Ethidium D005260:Female D005786:Gene Expression Regulation D005904:Glial Fibrillary Acidic Protein D006614:Hindlimb D017493:Leukocyte Common Antigens D051379:Mice D008810:Mice, Inbred C57BL D046529:Microscopy, Electron, Transmission D009043:Motor Activity D009413:Nerve Fibers, Myelinated D016900:Neurofilament Proteins D020127:Recovery of Function D012720:Severity of Illness Index D013116:Spinal Cord D013119:Spinal Cord Injuries D013997:Time Factors
Ethidium bromide Ethidium bromide Demyelination Inflammation ventral white matter Basso mouse scale electron microscopy (1)EB (10)PFA (11)SWM (12)ROI (13)IHC (14)BSA (15)NDS (16)TBS (17)NF-M (18)GFAP (19)MBP (2)mtDNA (20)EM (21)qRT-PCR (22)Fn1 (23)Gapdh (24)RW (25)SCI (26)BBB (27)MLR (28)MedRF (29)PLR (3)VLF (30)DLF (31)ACS (32)PCS (4)VC (5)VWM (6)EC (7)BMS (8)RI (9)PBS Basso, Beattie, and Bresnahan Locomotion Spared white matter Spinal cord injury anterior cord syndrome bovine serum albumin dorsolateral funiculus ethidium bromide fibronectin 1 glial fibrilary acidic protein glyceraldehyde 3-phosphate dehydrogenase immunohistochemistry iron eriochrome cyanine mesencephalic locomotor region mitochondrial DNA myelin basic protein neurofilament M normal donkey serum paraformaldehyde phosphate buffered saline pontomedullary locomotor region pontomedullary reticular formation posterior cord syndrome quantitative real-time polymerase chain reaction regions of interest regularity index running wheel spared white matter spinal cord injury tris buffered saline ventral column ventrolateral funiculus