title: Neuroprotection of early and short-time applying atorvastatin in the acute phase of cerebral ischemia: down-regulated 12/15-LOX, p38MAPK and cPLA2 expression, ameliorated BBB permeability.
abstract: BACKGROUND
  It has been proved that chronic administration and pre-treatment with atorvastatin could protect brain tissue against ischemic injury. However, little is known regarding the effect of atorvastatin in the acute phase of ischemic stroke. This study investigated the potential neuroprotective effects of atorvastatin and underlying mechanisms in vivo.
  
  
  METHODS
  Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO). Experiment 1 was used to evaluate time course expressions of 12/15-LOX, mitogen-activated protein kinase (MAPK), phosphorylated-p38MAPK (phospho-p38MAPK) and cytosolic phospholipase A2 (cPLA2) after cerebral ischemia, seven time points were included. Experiment 2 was used to detect atorvastatin's neuroprotection in the acute phase of ischemic stroke; atorvastatin was administered immediately after MCAO. Neurological deficit, brain water content and infarct size were measured at 24h after stoke. Immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to analyze the expression of 12/15-LOX, p38MAPK, phospho-p38MAPK and cPLA2. Experiment 3 was used to detect atorvastatin's influence on blood-brain barrier (BBB).
  
  
  RESULTS
  12/15-LOX, p38MAPK, phospho-p38MAPK and cPLA2 were up-regulated after cerebral ischemia. Compared with MCAO group, atorvastatin dramatically reduced brain water content and infarct sizes, and the over-expressions of 12/15-LOX, p38MAPK, phospho-p38MAPK and cPLA2 were significantly decreased in high dose group (20mg/kg, P<0.05). Meanwhile, extra-vascular IgG was not only reduced, but BBB permeability was also ameliorated.
  
  
  CONCLUSIONS
  Atorvastatin protected brain from damage caused by MCAO at the early stage; this effect may be through down-regulation of 12/15-LOX, p38MAPK and cPLA2 expressions, and ameliorating BBB permeability.
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Cui
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.forename: Lingling
authors.initials: L
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Du
mesh_terms: D000208:Acute Disease; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D000069059:Atorvastatin; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D054510:Phospholipases A2, Cytosolic / Q000378:metabolism; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C475064:12-15-lipoxygenase; D006538:Heptanoic Acids; D018696:Neuroprotective Agents; D011758:Pyrroles; D000069059:Atorvastatin; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D048051:p38 Mitogen-Activated Protein Kinases; D054510:Phospholipases A2, Cytosolic