Recent reports and our previous study suggest that mast cells play: a crucial role in the pathological processes that follow cerebral ischemia. In this study, the effect of mast cells on neuron injury after cerebral ischemia was determined by adding in vitro ischemia-induced supernatant from mast cells to neurons and PC 12 cells under the same conditions (oxygen-glucose deprivation, OGD). The degree of cell injury was evaluated by the 3-[4,5-dimethylthiazol-2-yll-2,5-dipheny-Itetrazolium bromide (MTT) assay. Mast cell-derived supernatant protected against OGD-induced injury of PC12 cells and neurons, and this protection was reversed by a histamine H, antagonist and by anti-histamine serum, but not by an H-2 antagonist. However, histamine and nerve growth factor (NGF) added separately or. together did not have protective effects against OGD-induced injury. These results indicate that mast cell-derived protection during in vitro ischemia is histamine-dependent, and involves cooperation with other mediators, but not NGF. (C) 2007 Elsevier Ireland Ltd. All rights reserved.