title: Status epilepticus-induced neuronal damage in the rat amygdaloid complex: distribution, time-course and mechanisms.
abstract: The present study was designed to elucidate the distribution, time-course and mechanism(s) of status epilepticus-induced neuronal damage in the rat amygdaloid complex. Status epilepticus was induced with kainate (9 mg/kg, i.p.), and the behavioral and electrographic seizure activity of each rat was monitored via cortical electrodes attached to a continuous video electrocorticogram system. Rats were subsequently perfused 1, 2, 4, 8, 16, 24 or 48 h after kainate injection. The first signs of amygdaloid damage were seen in rats perfused 4 h after kainate injection, though the severity and temporal appearance of damage varied substantially between the different amygdaloid nuclei and their subdivisions. Second, terminal transferase dUTP nick-end labeling (TUNEL)-positive nuclei and laddering of DNA in gel electrophoresis appeared in the amygdala 8 and 16 h after kainate, respectively. The distribution and density of TUNEL-positive nuclei in the different amygdaloid nuclei correlated with the distribution of neuronal damage in Thionin- and silver-stained sections. Third, the immunoreactivity of Bax protein, a promoter of apoptotic neuronal death, increased in the vulnerable medial division of the lateral nucleus prior to the appearance of argyrophilic neurons and TUNEL-positive nuclei. Fourth, the severity of neuronal damage progressed in some, but not all, amygdaloid regions throughout the 48-h follow-up, even though the occurrence of high-amplitude and frequency discharges, which are typically associated with behavioral seizure activity, extinguished after 7 h. These data show that status epilepticus-induced neuronal damage in the amygdala is a dynamic region-specific process, the severity of which depends on the duration of seizure activity. At least one mechanism underlying the damage involves apoptosis, which continues long after the behavioral and electrographic seizures have subsided.
authors.affiliation: A. I. Virtanen Institute, University of Kuopio, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Tuunanen
authors.forename: K
authors.initials: K
authors.lastname: Lukasiuk
authors.forename: T
authors.initials: T
authors.lastname: Halonen
authors.forename: A
authors.initials: A
authors.lastname: Pitkänen
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D017209:Apoptosis; D004569:Electroencephalography; D007608:Kainic Acid; D008297:Male; D009474:Neurons / Q000473:pathology* / Q000502:physiology*; D009928:Organ Specificity; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology*; D013997:Time Factors; D051028:bcl-2-Associated X Protein
chemical_list: C494828:Bax protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D007608:Kainic Acid