Morphological effects of excitatory amino acid analogs on primary astroglial cultures

In vivo administration of excitatory amino acids (excitotoxins) causes gliotoxicity in addition to neurotoxicity. The astrocyte reaction has been proposed to be secondary to neurotoxic effects, but this suggestion is based on circumstantial evidence. In the present study, this issue was addressed by examination of morphological alterations of astrocytes in primary culture to exposure of different excitotoxins. Two-week-old rat hippocampal cultures were exposed to the type agonists N-methyl-d-aspartate (NMDA), kainic acid (KA), quisqualate (QA) and to the mixed agonist glutamate (GLU). Agonists were included at 1 mM and exposure was continued for 22 h. NMDA-treated cultures did not differ from controls. However, KA induced a complex pattern of morphological reactions. Further, GLU and QA caused astrocyte swelling which was spontaneously reversed after GLU addition while QA killed astrocytes after 22 h of incubation. Excitotoxins induce astrocyte edema in vivo regardless of their receptor preference. The present study failed to disclose a similar stereotyped response, suggesting that in vivo gliotoxicity of excitotoxins is unrelated to direct effects on astroglia.