Effect of pitavastatin against expression of S100beta protein in the gerbil hippocampus after transient cerebral ischaemia.

Abstract

We investigated the immunohistochemical alterations of S100beta-, S100-, glial fibrillary acidic protein (GFAP)- and isolectin B4-positive cells in the hippocampus after 5 min of transient cerebral ischaemia in gerbils. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor pitavastatin against neuronal damage in the hippocampal CA1 sector after ischaemia. Severe neuronal damage was observed in the hippocampal CA1 pyramidal neurons from 5 days after ischaemia. GFAP-positive cells increased gradually in the hippocampus from 5 days after ischaemia. Five and 14 days after ischaemia, significant increases in the number of GFAP-positive cells and isolectin B4-positive cells were observed in the hippocampal CA1 and CA3 sector. Mild increases in the number of S100 and S100beta-positive cells were observed in the hippocampal CA1 sector from 1 h to 2 days after ischaemia. Thereafter, S100beta-positive cells increased in the hippocampal CA1 sector after ischaemia, whereas S100-positive cells decreased in this region. In our double-labelled immunostainings, S100 and S100beta immunoreactivity was found in GFAP-positive astrocytes, but not in isolectin B4-positive microglia. Pharmacological study showed that HMG-CoA reductase inhibitor, pitavastatin, can protect against the hippocampal CA1 neuronal damage after ischaemia. This drug also prevented increases in the number of GFAP-positive astrocytes, isolectin B4-positive microglia, S100-positive astrocytes and S100beta-positive astrocytes after ischaemia. The present study demonstrates that pitavastatin can decrease the neuronal damage of hippocampal CA1 sector after ischaemia. This beneficial effect may be, at least in part, mediated by inhibiting the expression of astrocytic activation in the hippocampus at the acute phase after ischaemia. Thus the modulation of astrocytic activation may offer a novel therapeutic strategy of ischaemic brain damage.