pitavastatin and Brain-Ischemia

It remains unclear whether the decrease in the ADMA level associated with statin treatment results from the LDL-C-lowering effect or the pleiotropic effects of statins. A prospective, controlled study was conducted to examine whether statin treatment affects serum ADMA concentrations in ischemic stroke patients.. Consecutive outpatients with non-cardiogenic ischemic stroke who had never been treated with statins and whose LDL-cholesterol level was higher than 140 mg/dL were enrolled and compared with control patients whose LDL-cholesterol level was lower than 140 mg/dL. Overall, 114 patients were enrolled in the study (56 and 58 in statin-treated and non-statin-treated groups, respectively). Patients in the statin group were treated with pravastatin 10 mg/day (n=15), fluvastatin 20 mg/day (n=14), pitavastatin 1 mg/day (n=14), or atorvastatin 10 mg/day (n=13).. The serum ADMA concentration and LDL-C level were significantly decreased by statin treatment (p=0.003 and p< 0.001, respectively), and the ADMA concentration in subjects treated with statins was significantly lower than that of the control (p=0.028). Multiple linear regression analysis showed that age (β=0.26, p< 0.05) and statin use (β=-0.20, p< 0.05) were independently associated with the ADMA level.. A significant relation between statin treatment and decreased levels of ADMA was demonstrated in ischemic stroke patients with an adequately controlled lipid profile, suggesting the statin treatment might prevent atherosclerotic disease in ischemic stroke patients through suppression of ADMA concentration.

Topics: Aged; Aged, 80 and over; Arginine; Atherosclerosis; Atorvastatin; Brain Ischemia; Cholesterol, LDL; Fatty Acids, Monounsaturated; Female; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Linear Models; Male; Middle Aged; Pravastatin; Prospective Studies; Pyrroles; Quinolines; Stroke

We investigated the neuroprotective effects of a novel 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (pitavastatin) on ischemic neuronal damage in gerbils using immunohistochemistry. The animals were allowed to survive for 14 days after 5 min of ischemia induced by bilateral occlusion of the common carotid arteries. Five days after ischemia, severe neuronal cell loss was observed in the hippocampal CA1 sector. Prophylactic treatment with pitavastatin dose-dependently prevented the hippocampal CA1 neuronal cell loss 5 days after ischemia. Immunohistochemical study did not show the change of nNOS and iNOS expression in the hippocampus except for, in a few regions, up to 1 day after ischemia. Thereafter, the expression of iNOS was observed in the hippocampal CA1 sector 5 and 14 days after ischemia. In contrast, the expression of nNOS and eNOS gradually decreased in the hippocampal CA1 sector up to 14 days after ischemia. Prophylactic treatment with pitavastatin also prevented the expression of iNOS and the decrease of eNOS expression and the number of nNOS-positive cells in the hippocampal CA1 sector 5 days after ischemia. However, prophylactic treatment with pitavastatin at a dose of 10 mg kg(-1) did not change the immunoreactivity of iNOS and nNOS in the hippocampus at an early phase after ischemia. In contrast, this drug prevented the reduction of eNOS immunoreactivity in the hippocampal CA1 neurons at an early phase after ischemia. These findings demonstrate that the HMG-CoA reductase inhibitor pitavastatin can protect hippocampal CA1 neurons after transient forebrain ischemia through up-regulation of eNOS expression in this region. Thus pharmacological modulation of eNOS expression may offer a novel therapeutic strategy for cerebral ischemic stroke.

Topics: Animals; Brain Ischemia; Gerbillinae; Hippocampus; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Neurons; Neuroprotective Agents; Quinolines