title: Development of cytotoxic cerebral edema in rats following intracaudatum injection of tACPD, an agonist of metabotropic glutamate receptors.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Beijing Neurosurgical Institute, Beijing 100050, China. yuanff@sina.com
authors.forename: F
authors.initials: F
authors.lastname: Yuan
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Luo
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: B
authors.initials: B
authors.lastname: Qu
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000139:chemically induced / Q000209:etiology*; D003515:Cycloleucine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*
chemical_list: D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane