Summary: Purpose:The aim of the present study was to observe possible cortical abnormalities after repetitive pilocarpineinduced status epilepticus (SE) in rats during development.Methods: Wistar rats received intraperitoneal injection of pilocarpine hydrochloride 2% (380 mg/kg) at P7, P8, and P9. All experimental rats displayed SE after pilocarpine injections. Rats were killed at P10 and P35, and immunocytochemistry procedures were performed on 50-µm vibratome sections, by using antibodies against nonphosphorylated neurofilament (SMI-311), parvalbumin (PV), calbindin (CB), calretinin (CR), and glutamate decarboxylase (GAD-65). Selected sections were used for the TUNEL method and double-labeling experiments, with different mixtures of the same markers.
Results:The major findings of the present work were (a) altered intracortical circuitry development; (b) anticipation of PV immunoreactivity in neocortical interneurons; (c) increased GAD-65 immunoreactivity; and (d) reduced neocortical apoptotic process.Conclusions: From these results, we suggest that previously healthy brain, without genetic abnormalities, might develop an "acquired" disruption of cortical development whose evolution reproduces some characteristics of the childhood epilepsies associated with cognitive impairment. Key Words: Immature brain-Early insult-Apoptosis-Neocortex-Interneurons.In humans, the incidence of seizures is higher in the first year of life and decreases until adulthood (1,2). Although most of the early-life seizures are inherently benign, symptomatic febrile or hypoxic seizures are present in the history of many patients with temporal lobe epilepsy (TLE) and are believed to be associated with an underlying progressive epileptogenic process (3). Despite increasing knowledge of basic epileptology, the role of early-life seizures in the development of TLE remains an open question.In rats, neonatal seizures induce a range of hippocampal changes, such as glia activation and cytokine increase (4), altered glutamate and γ -aminobutyric acid (GABA)(A)-receptor gene immunoreactivity (5), persistent changes in intrinsic properties of CA1 cells (6), long-term behavioral deficits (7), and reduced hippocampal neurogenesis (8). Nevertheless, several studies have shown that the immature brain is resistant to seizure-induced hippocampal neuronal cell loss (9-12) and synaptic reorganization (11,13,14). Despite hippocampal resistance to neuronal Address correspondence and reprint requests to Dr. A. V. Silva at Lab Neurologia Experimental UNIFESP-EPM, Rua Botucatú, 862, CEP 04023-900 São Paulo, SP, Brazil. E-mail: valotta.nexp@epm.br damage during early development, Santos and colleagues (15,16) recently demonstrated that multiple episodes of pilocarpine-induced status epilepticus (SE) in developing rats (P7-P9) led to progressive neocortical/hippocampal epileptiform activity, persistent in vitro hyperexcitability, increased hippocampal/thalamic apoptosis, and severe cognitive impairment in adulthood.In contrast to adult rats that develop hippocam...