A re-assessment of minocycline as a neuroprotective agent in a rat spinal cord contusion model.
This study was initiated due to an NIH "Facilities of Research--Spinal Cord Injury" contract to support independent replication of published studies that could be considered for a clinical trial in time. Minocycline has been shown to have neuroprotective effects in models of central nervous system injury, including in a contusive spinal cord injury (SCI) model at the thoracic level. Beneficial effects of minocycline treatment included a significant improvement in locomotor behavior and reduced histopathological changes [Lee, S.M., Yune, T.Y., Kim, S.J., Park, D.O.W., Lee, Y.K., Kim, Y.C., Oh, Y.J., Markelonis, G.J., Oh, T.H., 2003. Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat. J Neurotrauma. 20, 1017-1027.] To verify these important observations, we repeated this study in our laboratory. The NYU (MASCIS) Impactor was used to produce a moderate cord lesion at the vertebral level T9-T10 (height 12.5 mm, weight 10 g), (n=45), followed by administration of minocycline, 90 mg/kg (group 1: minocycline IP, n=15; group 2: minocycline IV, n=15; group 3: vehicle IP, n=8; group 4: vehicle IV, n=7) immediately after surgery and followed by two more doses of 45 mg/kg/IP at 12 h and 24 h. Open field locomotion (BBB) and subscores were examined up to 6 weeks after SCI and cords were processed for quantitative histopathological analysis. Administration of minocycline after SCI did not lead to significant behavioral or histopathological improvement. Although positive effects with minocycline have been reported in several animal models of injury with different drug administration schemes, the use of minocycline following contusive SCI requires further investigation before clinical trials are implemented.
The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, 1095 NW 14(th) Terrace, LPLC 2-30, Miami, FL 33136, USA.
Alberto
A
Pinzon
Alexander
A
Marcillo
Ada
A
Quintana
Sarah
S
Stamler
Mary Bartlett
MB
Bunge
Helen M
HM
Bramlett
W Dalton
WD
Dietrich
D000818:Animals; D004195:Disease Models, Animal; D004525:Efferent Pathways / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D007794:Lameness, Animal / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008911:Minocycline / Q000494:pharmacology* / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010243:Paralysis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D015203:Reproducibility of Results; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013904:Thoracic Vertebrae; D017211:Treatment Failure
D018696:Neuroprotective Agents; D008911:Minocycline