TY - JOUR T1 - Patterns of Status Epilepticus-Induced Neuronal Injury during Development and Long-Term Consequences JF - The Journal of Neuroscience JO - J. Neurosci. SP - 8382 LP - 8393 DO - 10.1523/JNEUROSCI.18-20-08382.1998 VL - 18 IS - 20 AU - Raman Sankar AU - Don H. Shin AU - Hantao Liu AU - Andrey Mazarati AU - Anne Pereira de Vasconcelos AU - Claude G. Wasterlain Y1 - 1998/10/15 UR - http://www.jneurosci.org/content/18/20/8382.abstract N2 - The lithium–pilocarpine model of status epilepticus (SE) was used to study the type and distribution of seizure-induced neuronal injury in the rat and its consequences during development. Cell death was evaluated in hematoxylin- and eosin-stained sections and by electron microscopy. Damage to the CA1 neurons was maximal in the 2- and 3-week-old pups and decreased as a function of age. On the other hand, damage to the hilar and CA3 neurons was minimal in the 2-week-old rat pups but reached an adult-like pattern in the 3-week-old animals, and damage to amygdalar neurons increased progressively with age. The 3-week-old animals also demonstrated vulnerability of the dentate granule cells. To evaluate neuronal apoptosis, we used terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) stain, confocal fluorescence microscopy of ethidium bromide-stained sections, electron microscopy, and DNA electrophoresis. Neurons displaying all of those features of apoptotic death in response to SE were seen in the CA1 region of the 2-week-old pups and in the hilar border of the dentate granule cells of the 3-week-old animals. Some (3/11) of the animals that underwent SE at 2 weeks of age and most of the animals that underwent SE at 3 or 4 weeks of age (8/11 and 6/8, respectively) developed spontaneous seizures later in life; the latter showed SE-induced synaptic reorganization as demonstrated by Timm methodology. These results provide strong evidence for the vulnerability of the immature brain to seizure-induced damage, which bears features of both necrotic and apoptotic death and contributes to synaptic reorganization and the development of chronic epilepsy. ER -