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Attenuation of acute inflammatory response by atorvastatin after spinal cord injury in rats
Author(s) -
Pannu Ravinder,
Barbosa Ernest,
Singh Avtar K.,
Singh Inderjit
Publication year - 2004
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20345
Subject(s) - atorvastatin , medicine , inflammatory response , spinal cord injury , spinal cord , anesthesia , pharmacology , inflammation , psychiatry
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. © 2004 Wiley‐Liss, Inc.