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.


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.
Yuan
F
F
Beijing Neurosurgical Institute, Beijing 100050, China. yuanff@sina.com
Wang
T
T
Luo
L
L
Sun
Y
Y
Zhang
L
L
Qu
B
B
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*
D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane