A re-assessment of minocycline as a neuroprotective agent in a rat spinal cord contusion model

Alberto Pinzon, Alexander Marcillo, Ada Quintana, Sarah Stamler, Mary B Bunge, Helen Bramlett, W. Dalton Dietrich

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)146-151
Number of pages6
JournalBrain Research
Volume1243
DOIs
StatePublished - Dec 3 2008

Fingerprint

Minocycline
Neuroprotective Agents
Spinal Cord Injuries
Clinical Trials
Nervous System Trauma
Locomotion
Contracts
Cell Death
Thorax
Central Nervous System
Animal Models
Weights and Measures

Keywords

  • Behavioral outcome
  • Minocycline
  • Neuroprotection
  • Spinal cord injury

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

A re-assessment of minocycline as a neuroprotective agent in a rat spinal cord contusion model. / Pinzon, Alberto; Marcillo, Alexander; Quintana, Ada; Stamler, Sarah; Bunge, Mary B; Bramlett, Helen; Dalton Dietrich, W.

In: Brain Research, Vol. 1243, 03.12.2008, p. 146-151.

Research output: Contribution to journalArticle

Pinzon, Alberto ; Marcillo, Alexander ; Quintana, Ada ; Stamler, Sarah ; Bunge, Mary B ; Bramlett, Helen ; Dalton Dietrich, W. / A re-assessment of minocycline as a neuroprotective agent in a rat spinal cord contusion model. In: Brain Research. 2008 ; Vol. 1243. pp. 146-151.
@article{b2a9c882341c42109960bc0947302066,
title = "A re-assessment of minocycline as a neuroprotective agent in a rat spinal cord contusion model",
abstract = "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.",
keywords = "Behavioral outcome, Minocycline, Neuroprotection, Spinal cord injury",
author = "Alberto Pinzon and Alexander Marcillo and Ada Quintana and Sarah Stamler and Bunge, {Mary B} and Helen Bramlett and {Dalton Dietrich}, W.",
year = "2008",
month = "12",
day = "3",
doi = "10.1016/j.brainres.2008.09.047",
language = "English",
volume = "1243",
pages = "146--151",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",

}

TY - JOUR

T1 - A re-assessment of minocycline as a neuroprotective agent in a rat spinal cord contusion model

AU - Pinzon, Alberto

AU - Marcillo, Alexander

AU - Quintana, Ada

AU - Stamler, Sarah

AU - Bunge, Mary B

AU - Bramlett, Helen

AU - Dalton Dietrich, W.

PY - 2008/12/3

Y1 - 2008/12/3

N2 - 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.

AB - 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.

KW - Behavioral outcome

KW - Minocycline

KW - Neuroprotection

KW - Spinal cord injury

UR - http://www.scopus.com/inward/record.url?scp=55649088905&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=55649088905&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2008.09.047

DO - 10.1016/j.brainres.2008.09.047

M3 - Article

C2 - 18838063

AN - SCOPUS:55649088905

VL - 1243

SP - 146

EP - 151

JO - Brain Research

JF - Brain Research

SN - 0006-8993

ER -