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Attenuation of acute inflammatory response by atorvastatin after spinal cord injury in rats.
J Neurosci Res. 2005 Feb 01; 79(3):340-50.JN

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 alpha (TNFalpha) and interleukin 1beta (IL-1beta) 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, TNFalpha, and IL-1beta 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.

Authors+Show Affiliations

Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina 29425, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15605375

Citation

Pannu, Ravinder, et al. "Attenuation of Acute Inflammatory Response By Atorvastatin After Spinal Cord Injury in Rats." Journal of Neuroscience Research, vol. 79, no. 3, 2005, pp. 340-50.
Pannu R, Barbosa E, Singh AK, et al. Attenuation of acute inflammatory response by atorvastatin after spinal cord injury in rats. J Neurosci Res. 2005;79(3):340-50.
Pannu, R., Barbosa, E., Singh, A. K., & Singh, I. (2005). Attenuation of acute inflammatory response by atorvastatin after spinal cord injury in rats. Journal of Neuroscience Research, 79(3), 340-50.
Pannu R, et al. Attenuation of Acute Inflammatory Response By Atorvastatin After Spinal Cord Injury in Rats. J Neurosci Res. 2005 Feb 1;79(3):340-50. PubMed PMID: 15605375.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Attenuation of acute inflammatory response by atorvastatin after spinal cord injury in rats. AU - Pannu,Ravinder, AU - Barbosa,Ernest, AU - Singh,Avtar K, AU - Singh,Inderjit, PY - 2004/12/18/pubmed PY - 2005/6/11/medline PY - 2004/12/18/entrez SP - 340 EP - 50 JF - Journal of neuroscience research JO - J Neurosci Res VL - 79 IS - 3 N2 - 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 alpha (TNFalpha) and interleukin 1beta (IL-1beta) 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, TNFalpha, and IL-1beta 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. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/15605375/Attenuation_of_acute_inflammatory_response_by_atorvastatin_after_spinal_cord_injury_in_rats_ L2 - https://doi.org/10.1002/jnr.20345 DB - PRIME DP - Unbound Medicine ER -