Expression of death-related proteins in dentate granule cells in human bacterial meningitis

Neuronal apoptosis in the dentate gyrus has been observed in animal models of bacterial meningitis and in humans dying in the course of the disease. To evaluate the mechanisms of neuronal cell death, hippocampal sections of 20 patients dying from bacterial meningitis were investigated by immunohistochemistry using antibodies against the proform of caspase-3 and the active enzyme, bcl-2, bax and p53. In the dentate granule cell layer, the median density of neurons with an apoptotic morphology was 7.6/mm(2) (0-15.6/mm(2)). The median density of immunoreactive neurons was 2.3/mm(2) (procaspase-3), 0.9/mm(2) (activated caspase-3), 1.8/mm(2) (bcl-2), 1.1/mm(2) (bax) and 0.4/mm(2) (p53). 80% of neurons immunoreactive for active caspase-3 had an apoptotic morphology, whereas only 10% of all procaspase-3 stained neurons showed signs of apoptosis. Apoptotic cell death is present in humans dying in the course of bacterial meningitis in the dentate gyrus of the Formatio hippocampi. Neuronal expression of caspase-3, bcl-2 and bax suggests an involvement of these proteins in neuronal death.