Online citations, reference lists, and bibliographies.
Referencing for people who value simplicity, privacy, and speed.
Get Citationsy
← Back to Search

Minocycline Protects Motor But Not Autonomic Neurons After Cauda Equina Injury

T. Hoang, M. Akhavan, J. Wu, L. Havton
Published 2008 · Medicine

Save to my Library
Download PDF
Analyze on Scholarcy Visualize in Litmaps
Share
Reduce the time it takes to create your bibliography by a factor of 10 by using the world’s favourite reference manager
Time to take this seriously.
Get Citationsy
Conus medullaris/cauda equina injuries typically result in loss of bladder, bowel, and sexual functions, partly as a consequence of autonomic and motor neuron death. To mimic these injuries, we previously developed a rodent lumbosacral ventral root avulsion (VRA) injury model, where both autonomic and motor neurons progressively die over several weeks. Here, we investigate whether minocycline, an antibiotic with putative neuroprotective effects, may rescue degenerating autonomic and motor neurons after VRA injury. Adult female rats underwent lumbosacral VRA injuries followed by a 2-week treatment with either minocycline or vehicle injected intraperitoneally. The sacral segment of the spinal cord was studied immunohistochemically using choline acetyltransferase (ChAT) and activated caspase-3 at 4 weeks post-operatively. Minocycline increased the survival of motoneurons but not preganglionic parasympathetic neurons (PPNs). Further investigations demonstrated that a larger proportion of motoneurons expressed activated caspase-3 compared to PPNs after VRA injury and indicated an association with minocycline’s differential neuroprotective effect. Our findings suggest that minocycline may protect degenerating motoneurons and expand the therapeutic window of opportunity for surgical repair of proximal root lesions affecting spinal motoneurons.
This paper references
10.1016/S0074-7742(08)60183-X
The Axon Reaction: A Review of the Principal Features of Perikaryal Responses to Axon Injury
Lieberman Ar (1971)
10.1002/glia.20140
Constitutive nuclear localization of activated caspase 3 in subpopulations of the astroglial family of cells
M. H. Noyan-Ashraf (2005)
10.1002/NEU.10026
Injury-induced spinal motor neuron apoptosis is preceded by DNA single-strand breaks and is p53- and Bax-dependent.
L. Martin (2002)
10.1016/0304-3940(95)12078-I
Brain-derived neurotrophic factor promotes survival and blocks nitric oxide synthase expression in adult rat spinal motoneurons after ventral root avulsion
L. Novikov (1995)
10.1016/S0166-2236(96)01000-4
The c-Jun transcription factor – bipotential mediator of neuronal death, survival and regeneration
T. Herdegen (1997)
10.1016/j.neulet.2005.10.037
Complement activation after lumbosacral ventral root avulsion injury
M. Ohlsson (2006)
10.3171/JNS.2000.93.2.0237
Analysis of aqueductal cerebrospinal fluid flow after endoscopic aqueductoplasty by using cine phase-contrast magnetic resonance imaging.
H. Schroeder (2000)
10.1177/1073858405275175
Minocycline as a Neuroprotective Agent
D. P. Stirling (2005)
10.1016/S0166-2236(98)01362-9
Stereological methods for estimating the total number of neurons and synapses: issues of precision and bias
M. West (1999)
10.1002/ana.10614
Minocycline and doxycycline are not beneficial in a model of Huntington's disease
D. Smith (2003)
10.1002/CNE.902060103
Afferent and efferent connections of the rat tail flick reflex (a model used to analyze pain control mechanisms)
M. L. Grossman (1982)
10.1016/j.pain.2005.12.023
Activation of glia and microglial p38 MAPK in medullary dorsal horn contributes to tactile hypersensitivity following trigeminal sensory nerve injury
Z. G. Piao (2006)
10.1016/j.jneumeth.2004.09.031
Titanium mesh implantation—A method to stabilize the spine and protect the spinal cord following a multilevel laminectomy in the adult rat
J. H. Nieto (2005)
10.1073/PNAS.95.26.15769
Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia.
J. Yrjänheikki (1998)
10.1523/JNEUROSCI.1259-06.2006
Functional Reinnervation of the Rat Lower Urinary Tract after Cauda Equina Injury and Repair
T. Hoang (2006)
10.1016/0306-4522(89)90144-9
Motoneurons reinnervate skeletal muscle after ventral root implantation into the spinal cord of the cat
S. Cullheim (1989)
10.1038/417074a
Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice
S. Zhu (2002)
10.1523/JNEUROSCI.1661-07.2007
Minocycline Alleviates Death of Oligodendrocytes by Inhibiting Pro-Nerve Growth Factor Production in Microglia after Spinal Cord Injury
T. Y. Yune (2007)
10.1097/00001756-200103050-00022
Caspase inhibitors promote the survival of avulsed spinal motoneurons in neonatal rats
Y. M. Chan (2001)
10.1016/0006-8993(88)90635-X
Loss of transmitter-associated enzyme staining following axotomy does not indicate death of brainstem cholinergic neurons
B. Lams (1988)
10.1016/j.expneurol.2006.11.003
At-level neuropathic pain is induced by lumbosacral ventral root avulsion injury and ameliorated by root reimplantation into the spinal cord
A. Bigbee (2007)
10.1006/exnr.2002.7897
Effect of Lumbar 5 Ventral Root Transection on Pain Behaviors: A Novel Rat Model for Neuropathic Pain without Axotomy of Primary Sensory Neurons
L. Li (2002)
10.1002/NEU.480270410
Differential regulation of motor neuron survival and choline acetyltransferase expression following axotomy.
S. Kou (1995)
10.1089/089771503770195867
Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat.
S. Lee (2003)
10.1523/JNEUROSCI.5275-03.2004
Minocycline Treatment Reduces Delayed Oligodendrocyte Death, Attenuates Axonal Dieback, and Improves Functional Outcome after Spinal Cord Injury
D. P. Stirling (2004)
10.1016/S0306-4522(98)00562-4
Re-expression of p75NTR by adult motor neurons after axotomy is triggered by retrograde transport of a positive signal from axons regrowing through damaged or denervated peripheral nerve tissue
K. V. Bussmann (1999)
10.1016/J.NBD.2004.07.012
Clinical potential of minocycline for neurodegenerative disorders
D. Blum (2004)
10.1111/j.1471-4159.2006.03799.x
Minocycline neuroprotects, reduces microgliosis, and inhibits caspase protease expression early after spinal cord injury
B. Festoff (2006)
10.1212/01.WNL.0000133403.30559.FF
Minocycline safety and tolerability in Huntington disease
(2004)
10.1097/00001756-200402090-00012
Differential expression of mGluR5 in human lumbosacral motoneurons
J. Anneser (2004)
10.1124/JPET.103.052407
Inhibition of Microglial Activation Attenuates the Development but Not Existing Hypersensitivity in a Rat Model of Neuropathy
V. Raghavendra (2003)
10.1016/j.nbd.2005.03.019
Minocycline fails to protect cerebellar granular cell cultures against malonate-induced cell death
F. J. Fernandez-Gomez (2005)
10.1002/(SICI)1096-9861(19960101)364:1<6::AID-CNE2>3.0.CO;2-9
Methods for determining numbers of cells and synapses: A case for more uniform standards of review
R. Coggeshall (1996)
10.1002/CNE.903420105
Ventral root avulsion: An experimental model of death of adult motor neurons
V. Koliatsos (1994)
10.1002/CNE.903630207
Axotomy induces a different modulation of both low‐affinity nerve growth factor receptor and choline acetyltransferase between adult rat spinal and brainstem motoneurons
M. Rende (1995)
10.1016/S0022-510X(96)05313-0
Involvement of Onuf's nucleus in amyotrophic lateral sclerosis
T. Kihira (1997)
10.1016/s0074-7742(08)60183-x
The axon reaction: a review of the principal features of perikaryal responses to axon injury.
A. Lieberman (1971)
E V ect of lumbar 5 ventral root transection on pain behaviors : A novel rat model for neuropathic pain without axotomy to primary sensory neurons
L Li (2002)
10.1038/SC.1994.13
International Standards for Neurological and Functional Classification of Spinal Cord Injury. American Spinal Injury Association.
J. Ditunno (1997)
10.1073/PNAS.0306239101
Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury.
Y. Teng (2004)
10.1002/cne.10928
Autonomic and motor neuron death is progressive and parallel in a lumbosacral ventral root avulsion model of cauda equina injury
T. Hoang (2003)
10.1016/S0079-6123(05)52012-0
Novel repair strategies to restore bladder function following cauda equina/conus medullaris injuries.
T. Hoang (2006)
10.1016/S0020-1383(97)00080-6
Lumbosacral nerve root avulsion.
C. H. Chin (1997)
10.1038/sc.1994.13
The International Standards Booklet for Neurological and Functional Classification of Spinal Cord Injury
J. Ditunno (1994)
10.1002/(SICI)1096-9861(19980629)396:2<158::AID-CNE2>3.0.CO;2-#
Characterization of spinal motoneuron degeneration following different types of peripheral nerve injury in neonatal and adult mice
L. Li (1998)
10.1097/01.nrl.0000106920.84668.37
Programmed Cell Death in Amyotrophic Lateral Sclerosis: a Mechanism of Pathogenic and Therapeutic Importance
S. Przedborski (2004)
10.1111/J.1748-1716.1986.TB08024.X
Reinnervation of hind limb muscles after ventral root avulsion and implantation in the lumbar spinal cord of the adult rat.
T. Carlstedt (1986)
10.1002/CNE.901920313
Organization of the motoneurons innervating the pelvic muscles of the male rat
H. D. Schrøder (1980)
10.3171/SPI.2000.93.2.0237
Spinal nerve root repair and reimplantation of avulsed ventral roots into the spinal cord after brachial plexus injury.
T. Carlstedt (2000)
10.1016/S0079-6123(05)52005-3
Mechanisms underlying the recovery of lower urinary tract function following spinal cord injury.
W. D. de Groat (2006)
10.1038/sj.sc.3100432
International Standards for Neurological and Functional Classification of Spinal Cord Injury
F. Maynard (1997)



This paper is referenced by
10.1016/j.pharmthera.2011.05.001
Pharmacological interventions for spinal cord injury: where do we stand? How might we step forward?
A. Rabchevsky (2011)
10.1111/ejn.13089
Clinical and neurobiological advances in promoting regeneration of the ventral root avulsion lesion
R. Eggers (2016)
10.1016/j.brainres.2008.09.047
A re-assessment of minocycline as a neuroprotective agent in a rat spinal cord contusion model
A. Pinzon (2008)
Chapter 11 Mesenchymal Stem Cells in Spinal Cord Injury
R. Pal (2017)
10.3389/fneur.2016.00135
New Treatments for Spinal Nerve Root Avulsion Injury
T. Carlstedt (2016)
10.1111/jne.12031
Distribution of Androgen and Oestrogen Receptors‐α in the Seminal Vesicle‐Related Spinal Neurones in Male Rats
X. Sun (2013)
10.1016/j.expneurol.2016.05.026
A ventral root avulsion injury model for neurogenic underactive bladder studies
Huiyi H Chang (2016)
10.21315/mjms2017.24.1.4
The Effects of Minocycline on Spinal Root Avulsion Injury in Rat Model.
T. Y. Chin (2017)
10.1097/WCO.0b013e328331b63f
Repair and rehabilitation of plexus and root avulsions in animal models and patients
L. Havton (2009)
10.5772/58323
Mesenchymal Stem Cells in Spinal Cord Injury
N. K. Venkataramanaa (2014)
10.1016/B978-0-444-52137-8.00021-8
The longitudinal spinal cord injury: lessons from intraspinal plexus, cauda equina and medullary conus lesions.
T. Carlstedt (2012)
10.3389/fbioe.2020.583184
GDNF Gene Therapy to Repair the Injured Peripheral Nerve
R. Eggers (2020)
Histological analysis of motoneuron survival and microglia inhibitionafter nerve root avulsion treated with nerve graft implantationand minocycline: an experimental study
Faizul H. Ghazali (2016)
10.5772/INTECHOPEN.82431
Nerve Root Reimplantation in Brachial Plexus Injuries
V. Vanaclocha-Vanaclocha (2019)
Chapter 4 Nerve Root Reimplantation in Brachial Plexus Injuries
V. Vanaclocha-Vanaclocha (2019)
10.1002/syn.20993
Granulocyte colony stimulating factor neuroprotective effects on spinal motoneurons after ventral root avulsion
Camila Marques De Freria (2012)
10.1016/j.jpain.2014.03.001
The effects of minocycline or riluzole treatment on spinal root avulsion-induced pain in adult rats.
D. Chew (2014)
Semantic Scholar Logo Some data provided by SemanticScholar