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

Lili Cui, Xiangjian Zhang, Rui Yang, Lina Wang, Lingling Liu, Min Li, Wei Du
Brain Research 2010 April 14, 1325: 164-73

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.

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