title: Might astrocytes play a role in maintaining the seizure-prone state?
abstract: The amygdala-kindling model is used to study complex partial epilepsy with secondary generalization. The present study was designed to (A) quantify astrocytic changes in the piriform cortex of amygdala-kindled subjects over time and (B) investigate the role that astrocytes might play in maintaining the seizure-prone state. In Study A, once the experimental subjects reached five stage 5 seizures, stimulation was stopped, and both kindled and control rats were allowed to survive for the interval appropriate to their group (7, 18, 30, or 90 days). Following each interval, the kindled and control animals were given 10 intraperitoneal injections of bromodeoxyuridine (BrdU) and sacrificed 24 h following the last injection. Significantly higher numbers of dividing astrocytes (identified by co-labeling for BrdU and to one of the astrocytic intermediate filament proteins glial fibrillary acidic protein or vimentin) were found in the kindled brains. All kindled groups had significantly higher numbers of double-labeled cells on the side contralateral to the stimulation site, except for those in the 90 day survival group. In Study B, rats were implanted with chemotrodes, were kindled as in Study A, and were subsequently infused with either saline or with L alpha-AA (to lesion astrocytes) during a further 25 stimulations (1/day). L alpha-AA infused rats had significantly diminished levels of behavioral seizures, higher after discharge thresholds, lower after discharge durations, and decreased numbers of double-labeled astrocytes in piriform cortex than did saline infused rats. Together, the data indicate that astrocytes may play a role in maintaining the seizure-prone state.
authors.affiliation: Institute of Medical Science, Medical Science Building, University of Toronto, Toronto, ON, Canada M5S 1A8. mvessal@stanford.edu
authors.forename: Mani
authors.initials: M
authors.lastname: Vessal
authors.forename: Chandrasagar B
authors.initials: CB
authors.lastname: Dugani
authors.forename: Dianand A
authors.initials: DA
authors.lastname: Solomon
authors.forename: W
authors.initials: W
authors.lastname: McIntyre Burnham
authors.forename: Gwen O
authors.initials: GO
authors.lastname: Ivy
mesh_terms: D015074:2-Aminoadipic Acid / Q000633:toxicity; D000679:Amygdala / Q000503:physiopathology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology*; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D012640:Seizures / Q000503:physiopathology*; D012720:Severity of Illness Index; D013997:Time Factors; D014746:Vimentin / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D014746:Vimentin; D015074:2-Aminoadipic Acid; D001973:Bromodeoxyuridine