Development of cytotoxic cerebral edema in rats following intracaudatum injection of tACPD, an agonist of metabotropic glutamate receptors

OBJECTIVE: To explore the involvement of metabotropic glutamate receptors (mGluRs) in the formation of cerebral edema. METHODS: Male Wistar rats weighing from 250 g to 300 g were used. Trans-1-aminocyclopentane-1, 3-diacarboxylic acid (tACPD), an agonist of mGluRs, was microinjected into the right caudatum. Brain water content was determined by a wet weight/dry weight technique and Na+, K+ and Ca2+ contents were measured by inductive Couple Plasma-9000 at 6 h, 24 h and 48 h post-injection. Extravasation of Evan's blue (EB) into the brain was determined as an indicator of disturbance in the blood-brain barrier (BBB) and endothelial cells. Histologic studies were performed under a Leitz microscope and a Philips EM208s electron microscope. RESULTS: Dose-dependent and time-related increase of brain water was induced after tACPD (10, 50, 500 and 1000 nmol) injection. A significant increase in Na+ and K+ content but not in Ca2+ content was observed. EB extravasation showed no blue stain, indicating no increase in BBB permeability induced by tACPD-injection. Electron microscope study confirmed this finding and revealed remarkable swelling of astrocytes especially endfoot processes of astrocytes around capillaries at 6 h after tACPD-injection. In addition, all changes mentioned above occurred in both caudatum. CONCLUSION: These results indicate that activation of mGluRs by tACPD injected into the caudatum induced cytotoxic brain edema and interfered with astrocyte K+ buffering. This may provide new clues for therapeutic intervention.