Massive astrocytic swelling in response to extracellular glutamate--a possible mechanism for post-traumatic brain swelling?

Little attention has been paid to the responses of astrocytes in the brain to the application of neurotoxic excitatory transmitters such as glutamate. We have developed a simple model to study the responses of cells within the cerebral cortex to neurotoxic levels of glutamate. After short periods of perfusion with glutamate, perivascular and interstitial astrocytes swell and become electron lucent. The astrocyte swelling extends, with increasing periods of perfusion, up to 400 um into the adjacent, intact neuropil. After 90 minutes of glutamate perfusion, intermediate filament bundles and glycogen granules occur within the astrocyte cytoplasm. We obtained no evidence for compromised blood flow. We suggest that astrocyte swelling serves to limit the diffusion of glutamate from the site of the lesion.