title: Atorvastatin protects GABAergic and dopaminergic neurons in the nigrostriatal system in an experimental rat model of transient focal cerebral ischemia.
abstract: BACKGROUND
  Cerebral ischemia is the third leading cause of death and the primary cause of permanent disability worldwide. Atorvastatin is a promising drug with neuroprotective effects that may be useful for the treatment of stroke. However, the effects of atorvastatin on specific neuronal populations within the nigrostriatal system following cerebral ischemia are unknown.
  
  
  OBJECTIVE
  To evaluate the effects of atorvastatin on dopaminergic and GABAergic neuronal populations in exofocal brain regions in a model of transient occlusion of the middle cerebral artery.
  
  
  METHODS
  Twenty-eight male eight-week-old Wistar rats were used in this study. Both sham and ischemic rats were treated with atorvastatin (10 mg/kg) or carboxymethylcellulose (placebo) by gavage at 6, 24, 48 and 72 hours post-reperfusion. We analyzed the immunoreactivity of glutamic acid decarboxylase and tyrosine hydroxylase in the globus pallidus, caudate putamen and substantia nigra.
  
  
  RESULTS
  We observed neurological damage and cell loss in the caudate putamen following ischemia. We also found an increase in tyrosine hydroxylase immunoreactivity in the medial globus pallidus and substantia nigra reticulata, as well as a decrease in glutamic acid decarboxylase immunoreactivity in the lateral globus pallidus in ischemic animals treated with a placebo. However, atorvastatin treatment was able to reverse these effects, significantly decreasing tyrosine hydroxylase levels in the medial globus pallidus and substantia nigra reticulata and significantly increasing glutamic acid decarboxylase levels in the lateral globus pallidus.
  
  
  CONCLUSIONS
  Our data suggest that post-ischemia treatment with atorvastatin can have neuro-protective effects in exofocal regions far from the ischemic core by modulating the GABAergic and dopaminergic neuronal populations in the nigrostriatal system, which could be useful for preventing neurological disorders.
authors: Grupo de Modelos Experimentales para las Ciencias Zoohumanas, Facultad de Ciencias Básicas, Universidad del Tolima, Ibagué, Colombia.
authors: Angélica María
authors: AM
authors: Sabogal
authors: Fundación Valle del Lili, Cali, Colombia.
authors: César Augusto
authors: CA
authors: Arango
authors: Grupo de Investigación en Enfermedades Neurodegenerativas, Departamento de Salud Animal, Facultad de Medicina Veterinaria, Universidad del Tolima, Ibagué, Ibagué, Colombia.
authors: Gloria Patricia
authors: GP
authors: Cardona
authors: Grupo de Neurociencias de Antioquia, Área de Neurobiología Celular y Molecular, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
authors: Ángel Enrique
authors: ÁE
authors: Céspedes
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D001522:Behavior, Animal; D003342:Corpus Striatum / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D004790:Enzyme Induction / Q000187:drug effects; D059330:GABAergic Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D005968:Glutamate Decarboxylase / Q000096:biosynthesis / Q000235:genetics; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009069:Movement Disorders / Q000209:etiology / Q000517:prevention & control; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D012678:Sensation Disorders / Q000209:etiology / Q000517:prevention & control; D013047:Specific Pathogen-Free Organisms; D013378:Substantia Nigra / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis / Q000235:genetics
chemical_list: D006538:Heptanoic Acids; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011758:Pyrroles; D000069059:Atorvastatin; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2