Attenuation of acute inflammatory response by atorvastatin after spinal cord injury in rats
- 16 December 2004
- journal article
- research article
- Published by Wiley in Journal of Neuroscience Research
- Vol. 79 (3), 340-350
- https://doi.org/10.1002/jnr.20345
Abstract
Spinal cord injury (SCI) is a devastating and complex clinical condition involving proinflammatory cytokines and nitric oxide toxicity that produces a predictable pattern of progressive injury entailing neuronal loss, axonal destruction, and demyelination at the site of impact. The involvement of proinflammatory cytokines and inducible nitric oxide synthase (iNOS) in exacerbation of SCI pathology is well documented. We have reported previously the antiinflammatory properties and immunomodulatory activities of statins (3-hydroxy-3-methylglutaryl [HMG]-CoA reductase inhibitors) in the animal model of multiple sclerosis, experimental allergic encephalitis (EAE). The present study was undertaken to investigate the efficacy of atorvastatin (Lipitor; LP) treatment in attenuating SCI-induced pathology. Immunohistochemical detection and real-time PCR analysis showed increased expression of iNOS, tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β) after SCI. In addition, neuronal apoptosis was detected 24 hr after injury followed by a profound increase in ED1-positive inflammatory infiltrates, glial fibrillary acidic protein (GFAP)-positive reactive astrocytes, and oligodendrocyte apoptosis by 1 week after SCI relative to control. LP treatment attenuated the SCI-induced iNOS, TNFα, and IL-1β expression. LP also provided protection against SCI-induced tissue necrosis, neuronal and oligodendrocyte apoptosis, demyelination, and reactive gliosis. Furthermore, rats treated with LP scored much higher on the locomotor rating scale after SCI (19.13 ± 0.53) than did untreated rats (9.04 ± 1.22). This study therefore reports the beneficial effect of atorvastatin for the treatment of SCI-related pathology and disability.Keywords
This publication has 75 references indexed in Scilit:
- Gene expression patterns for GDNF and its receptors in the human putamen affected by Parkinson's disease: A real-time PCR studyMolecular and Cellular Endocrinology, 2006
- The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune diseaseNature, 2002
- GTPase RhoB: An Early Predictor of Neuronal Death after Transient Focal Ischemia in MiceMolecular and Cellular Neuroscience, 2001
- Neuroprotection mediated by changes in the endothelial actin cytoskeletonJCI Insight, 2000
- Inducible Nitric Oxide Synthase Expression after Traumatic Brain Injury and Neuroprotection with Aminoguanidine Treatment in RatsNeurosurgery, 1998
- Nitric OxideJournal of SPINAL DISORDERS, 1998
- A Sensitive and Reliable Locomotor Rating Scale for Open Field Testing in RatsJournal of Neurotrauma, 1995
- Neurogenic inflammationTrends in Pharmacological Sciences, 1990
- Methylprednisolone in Spinal Cord Injury: The Possible Mechanism of ActionJournal of Neurotrauma, 1990
- Arachidonic Acid and Its Metabolites in Cerebral IschemiaaAnnals of the New York Academy of Sciences, 1989