Two different constituents of plasma increase cytosolic calcium selectively in neurons or glia of primary rat cerebellar cultures.

1. The ability of several serum fractions to increase the cytosolic calcium concentration ([Ca2+]i) was tested in rat cerebellar cells maintained in primary culture. 2. Serum filtered through an ultrafiltration membrane with 3000 Da molecular mass cut-off (filtered serum, FS) selectively stimulated neurons whereas dialysed serum (DS) selectively stimulated glia. 3. The effects of FS were due to glutamate as they were reproduced by N-methyl-D-aspartate (NMDA), blocked by NMDA receptor antagonists and prevented by enzymatic removal of glutamate. 4. The effects of DS on glia were not reproduced by platelet-activating factor, thrombin or bradykinin. They were not lost on heating or extraction with diethyl ether. They were reproduced by a methanol-chloroform-HCl extract from DS and by several commercial fraction V plasma albumins. 5. These [Ca2+]i-increasing factors present in blood could contribute to brain damage during ischaemia if they reached the brain interstitium on disruption of the blood-brain barrier.