Abstract
Spinal cord injury (SCI) is a highly debilitating pathology. Although innovative medical
care has been improved, drug therapies to counteract neuronal damage and promote regeneration
are limited.
An experimental mouse model of SCI was designed to examine the possible neuroprotective
role of the glucosinolate (RS)-glucoraphanin (RS-GRA), bioactivated with myrosinase enzyme (MYR-activated RS-GRA).
Methodologically, the injury was induced by application of an aneurysm clip (force
of 24g) for 1 min via four-level T5–T8 after laminectomy. MYR-activated RS-GRA was administered in mice (10 mg/kg i.p.) 1 and 6 h after the trauma, identified as the therapeutic intervention window.
The treatment with MYR-activated RS-GRA significantly decreased histological damage resulted by proinflammatory events
as well as by apoptosis cascade. Overall, by quantitative analysis of immunohistochemical
images, the neuroprotection has been quite evident. MYR-activated RS-GRA has given a histological quantification around zero in all determinations. Particularly,
looking at the strongest data obtained, regarding the glial fibrillary acidic protein
(GFAP), result the high tissue localization of this damage marker mediated by astrocyte
activity, estimated as about 80% of positive staining, was shot down by MYR-activated
RS-GRA treatment.
Taken together, our results show that MYR-activated RS-GRA could represent an interesting approach for the management of secondary damage
following SCI.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of the Neurological SciencesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Characterization of a new rat model of experimental combined neurotrauma.Shock. 2005; 23: 476-481
- Cell proliferation and replacement following contusive spinal cord injury.Glia. 2005; 50: 247-257
- The epidemiology and economics of spinal cord injury.Paraplegia. 1987; 25: 225-228
- Cell death in models of spinal cord injury.Prog Brain Res. 2002; 137: 37-47
- Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms.J Neurosurg. 1991; 75: 15-26
- Degenerative and regenerative mechanisms governing spinal cord injury.Neurobiol Dis. 2004; 15: 415-436
- Cell death and plasticity after experimental spinal cord injury.Prog Brain Res. 2000; 128: 9-21
- Post-traumatic inflammation following spinal cord injury.Spinal Cord. 2003; 41: 369-378
- The role of excitotoxicity in secondary mechanisms of spinal cord injury: a review with an emphasis on the implications for white matter degeneration.J Neurotrauma. 2004; 21: 754-774
- Oxidative stress, redox homeostasis and cellular stress response in Meniere's disease: role of vitagenes.Neurochem Res. 2010; 35: 2208-2217
- Current developments in spinal cord injury research.Spine J. 2002; 2: 116-128
- Resveratrol commonly displays hormesis: occurrence and biomedical significance.Hum Exp Toxicol. 2010; 29: 980-1015
- Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders.Antioxid Redox Signal. 2010; 13: 1763-1811
- Increased oxidative-related mechanisms in the spinal cord injury in old rats.Neurosci Lett. 2006; 393: 141-146
- Redox proteomics in aging rat brain: involvement of mitochondrial reduced glutathione status and mitochondrial protein oxidation in the aging process.J Neurosci Res. 2010; 88: 3498-3507
- The enzymic and chemically induced decomposition of glucosinolates.Phytochemistry. 2006; 67: 1053-1067
- Hydrolysis of glucosinolates using nylon-immobilized myrosinase to produce pure bioactive molecules.Biotechnol Bioeng. 2000; 68: 660-664
- The natural chemopreventive phytochemical R-sulforaphane is a far more potent inducer of the carcinogen-detoxifying enzyme systems in rat liver and lung than the S-isomer.Int J Cancer. 2011; 128: 2775-2782
- Vegetable and fruit consumption and lung cancer risk in the Netherlands Cohort Study on diet and cancer.Cancer Causes Control. 2000; 11: 101-115
- Cruciferous vegetable consumption and lung cancer risk: a systematic review.Cancer Epidemiol Biomarkers Prev. 2009; 18: 184-195
- Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway.Annu Rev Pharmacol Toxicol. 2007; 47: 89-116
- The cancer chemopreventive actions of phytochemicals derived from glucosinolates.Eur J Nutr. 2008; 47: 73-88
- Protective Role of (RS)-glucoraphanin bioactivated with myrosinase in an experimental model of multiple sclerosis.CNS Neurosci Ther. 2013; 19: 577-584
- Effect of duration of acute spinal cord compression in a new acute cord injury model in the rat.Surg Neurol. 1978; 10: 38-43
- Intact glucosinolates modulate hepatic cytochrome P450 and phase II conjugation activities and may contribute directly to the chemopreventive activity of cruciferous vegetables.Toxicology. 2010; 277: 74-85
- Enclosure VIII.Offic J Eur Commun. 1990; 170: 27-34
- An improved method for the purification of myrosinase and its physicochemical characterization.Arch Biochem Biophys. 1990; 280: 383-389
- Natural sulforaphane as a functional chemopreventive agent: including a review of isolation, purification and analysis methods.Crit Rev Biotechnol. 2012; 32: 218-234
- Molecular evidence for the involvement of PPAR-delta and PPAR-gamma in anti-inflammatory and neuroprotective activities of palmitoylethanolamide after spinal cord trauma.J Neuroinflammation. 2013; 10: 20
- Nrf2/ARE signaling pathway: key mediator in oxidative stress and potential therapeutic target in ALS.Neurol Res Int. 2012; 2012: 878030
- Pathophysiology and pharmacologic treatment of acute spinal cord injury.Spine J. 2004; 4: 451-464
- The NF-kappa B activation pathway: a paradigm in information transfer from membrane to nucleus.Sci STKE. 1999; 1999: RE1
- Nuclear factor (NF)-kappaB proteins: therapeutic targets.Ann Rheum Dis. 2004; 63: ii57-ii61
- A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes.Nature. 1992; 356: 768-774
- GFAP and astrogliosis.Brain Pathol. 1994; 4: 229-237
- Regulation of T-cell responses by CNS antigen-presenting cells: different roles for microglia and astrocytes.Immunol Today. 2000; 21: 141-147
- In situ hybridization analysis of glial fibrillary acidic protein mRNA reveals evidence of biphasic astrocyte activation during acute experimental autoimmune encephalomyelitis.Am J Pathol. 1996; 148: 889-896
- Robust regeneration of adult sensory axons in degenerating white matter of the adult rat spinal cord.J Neurosci. 1999; 19: 5810-5822
- Beneficial effects of Nrf2 overexpression in a mouse model of Alexander disease.J Neurosci. 2012; 32: 10507-10515
- Astrocyte-specific overexpression of Nrf2 protects striatal neurons from mitochondrial complex II inhibition.Toxicol Sci. 2010; 115: 557-568
- Apoptosis of oligodendrocytes occurs for long distances away from the primary injury after compression trauma to rat spinal cord.Acta Neuropathol. 1999; 98: 473-480
- Functional role and therapeutic implications of neuronal caspase-1 and -3 in a mouse model of traumatic spinal cord injury.Neuroscience. 2000; 99: 333-342
- The central role of Fas-ligand cell signaling in inflammatory lung diseases.J Cell Mol Med. 2004; 8: 285-293
- Inhibition of Fas-mediated apoptosis through administration of soluble Fas receptor improves functional outcome and reduces posttraumatic axonal degeneration after acute spinal cord injury.J Neurotrauma. 2006; 23: 604-616
- Inflammation and apoptosis: linked therapeutic targets in spinal cord injury.Trends Mol Med. 2004; 10: 580-583
- Induction of apoptosis by the Bcl-2 homologue Bak.Nature. 1995; 374: 733-736
- Widespread elimination of naturally occurring neuronal death in Bax-deficient mice.J Neurosci. 1998; 18: 1428-1439
Article info
Publication history
Published online: August 30, 2013
Accepted:
July 25,
2013
Received in revised form:
June 24,
2013
Received:
March 22,
2013
Identification
Copyright
© 2013 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
