[Atorvastatin-meloxicam association inhibits neuroinflammation and attenuates the cellular damage in cerebral ischemia by arterial embolism]

Biomedica. 2014 Jul-Sep;34(3):366-78. doi: 10.1590/S0120-41572014000300007.
[Article in Spanish]

Abstract

Introduction: Stroke is the second leading cause of death and the first cause of disability in the world, with more than 85% of the cases having ischemic origin.

Objective: To evaluate in an embolism model of stroke the effect of atorvastatin and meloxicam on neurons, astrocytes and microglia. This evaluation was done administering each medication individually and in association.

Materials and methods: Wistar rats were subjected to carotid arterial embolism and treatment with meloxicam and atorvastatin at 6, 24, 48 and 72 hours. Using immunohistochemistry, we evaluated the immunoreactivity of COX-2 protein, GFAP and OX-42 in neurons, astrocytes and microglia by densitometric and morphological studies. Data were evaluated by variance analysis and non-parametric multiple comparison.

Results: Cerebral ischemia by arterial embolism increased significantly the reactivity of microglia and astrocytes (p<0.001), whereas it was reduced by atorvastatin, meloxicam and their association. Ischemia produced astrocytic shortening, cellular thickening, protoplasmic rupture expansions (clasmatodendrosis) and microglial morphological changes characteristic of various activity stages. In perifocal areas, immunoreactivity of COX-2 was increased and in the ischemic focus it was reduced, while meloxicam and atorvastatin significantly reduced (p<0.001) perifocal immunoreactivity, restoring the marking of cyclooxygenase in the ischemic focus.

Conclusion: These results suggest that the meloxicam-atorvastatin association attenuates astrocytic and microglial response in the inflammatory process after cerebral ischemia by arterial embolism, reducing neurodegeneration and restoring the morphological and functional balance of nervous tissue .

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / pathology
  • Atorvastatin
  • Biomarkers
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / etiology
  • Brain Ischemia / pathology
  • CD11b Antigen / analysis
  • Carotid Stenosis / complications
  • Carotid Stenosis / pathology
  • Cyclooxygenase 2
  • Cyclooxygenase Inhibitors / administration & dosage
  • Cyclooxygenase Inhibitors / therapeutic use*
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Female
  • Glial Fibrillary Acidic Protein / analysis
  • Heptanoic Acids / administration & dosage
  • Heptanoic Acids / therapeutic use*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Inflammation
  • Intracranial Embolism / complications*
  • Intracranial Embolism / pathology
  • Meloxicam
  • Microglia / drug effects
  • Microglia / pathology
  • Nerve Degeneration / prevention & control*
  • Nerve Tissue Proteins / analysis
  • Pyrroles / administration & dosage
  • Pyrroles / therapeutic use*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Thiazines / administration & dosage
  • Thiazines / therapeutic use*
  • Thiazoles / administration & dosage
  • Thiazoles / therapeutic use*

Substances

  • Biomarkers
  • CD11b Antigen
  • Cyclooxygenase Inhibitors
  • Glial Fibrillary Acidic Protein
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Nerve Tissue Proteins
  • Pyrroles
  • Thiazines
  • Thiazoles
  • Atorvastatin
  • Cyclooxygenase 2
  • Meloxicam