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Rice et al. Neuroimmunol Neuroinflammation 2017;4:243-53 Neuroimmunology and
DOI: 10.20517/2347-8659.2017.51
Neuroinflammation

www.nnjournal.net
Original Article Open Access

Neuroprotection by minocycline in murine

traumatic spinal cord injury: analyses of

matrix metalloproteinases

Tiffany Rice , Jennifer E.A. Larsen , Hui Li , Robert K. Nuttall , Peter H. Larsen , Steven Casha , John Hurlbert ,
2*
2,4
2
2
1*
3
2
Dylan R. Edwards , V. Wee Yong 2
3
1 Department of Anesthesia, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
2 Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
3 School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK.
4 Division of Neurosurgery, University of Arizona, Tucson, AZ 85721, USA.
* Authors contributed equally.
Correspondence to: Dr. V. Wee Yong, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive, Calgary, Alberta T2N 4N1, Canada.
E-mail: vyong@ucalgary.ca
How to cite this article: Rice T, Larsen JEA, Li H, Nuttall RK, Larsen PH, Casha S, Hurlbert J, Edwards DR, Yong VW. Neuroprotection by
minocycline in murine traumatic spinal cord injury: analyses of matrix metalloproteinases. Neuroimmunol Neuroinflammation 2017;4:243-53.
ABSTRACT
Article history: Aim: Minocycline has neuroprotective activities in several models of neurological disorders
Received: 1 Oct 2017 including spinal cord injury (SCI) where it prevents axonal loss and improves functional
First Decision: 17 Oct 2017 recovery. There are still gaps of knowledge on minocycline in SCI including whether
Revised: 20 Nov 2017 it ameliorates neuronal loss at the focal site of trauma, and whether minocycline reduces
Accepted: 20 Nov 2017 the activity of matrix metalloproteinases (MMPs), a family of enzymes implicated in the
Published: 28 Nov 2017 pathophysiology of SCI. This study addressed these gaps. Methods: Mice were treated with
Key words: either minocycline or vehicle control after a spinal cord contusion. MMPs were compared
Minocycline, between the two groups using real time polymerase chain reaction and zymography.
matrix metalloproteinases, Immunohistochemistry was used to examine microglial activation and neuronal cell death.
spinal cord injury, Results: While several MMP members were elevated in the spinal cord following injury,
neuroprotection treatment with minocycline did not affect their expression. Importantly, minocycline reduced
the loss of neurons in the epicenter of damage to the spinal cord and in segments caudal and
rostral to the injury. Conclusion: Despite the inability of minocycline to alter MMPs, the
results of neuroprotection at the lesion site support the continued testing of minocycline as a
neuroprotective medication in experimental and clinical SCI.

INTRODUCTION decades.It has been proposed as a promising
neuroprotective agent in multiple central nervous
Minocycline, a synthetic derivative of tetracycline, system (CNS) pathologies including stroke,
has been used for the treatment of acne for several Huntington’s disease, amyotrophic lateral sclerosis
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