Abstracts

RATIONALE: Audiogenic seizures (AS) are a model of generalized tonic-clonic epilepsy that can be triggered by high-intensity sound stimulation. Behavioral and electrophysiological data indicate they are generated in the brainstem. However, following chronic AS, the so-called audiogenic kindling (AUK), recruitment of limbic structures is detected. Furthermore, in different models of epileptic seizures, it has been shown increased hippocampal neurogenesis, suggesting that the newly generated neurons might be part of a vast number of morphological and functional changes (e.g: cell loss, axonal sprouting) that could contribute to epileptogenesis. Here we present a preliminary study aimed to evaluate the occurrence of neurogenesis in the DG of Wistar Audiogenic Rats (WARs) submitted to AUK and expressing limbic seizures. METHODS:_Normal rats (n=3) and WARs (n=3) were stimulated with a bell sound (120 dB/1 min) 2/day for 14 days. Behavioral evaluation was done by means of brainstem and limbic seizure severity indexes. After the last stimulation, they received 4 injections of BrdU (50mg/kg, i.p.) 6-6 h and were perfused 24 h later. The brains were removed, post-fixed, cryoprotected and frozen sections of 40 ?m were processed for BrdU immuhistochemistry (Oncogene BrdU kit). RESULTS:_WARs presented a progression from brainstem to limbic seizures, but none of the control rats presented any type of seizures. Cell counts were done in 13 WAR and 9 control hippocampi in anterior and posterior levels. The average of BrdU-positive nuclei presented in the DG of WARs with more than 6 class 4/5 seizures (rearing and falling) showed statistically significant increase (p<0.004; Mann-Whitney test) when compared to controls. CONCLUSIONS:_Therefore, our data suggest that the hippocampus could be involved in limbic seizures evoked after audiogenic kindling. Additional behavioral and electrophysiological data from our own laboratory suggest this happens through activation of amygdala. Financial Support: FAPESP, CNPq, PROAP-CAPES, FAEPA, PRONEX