Abstracts

RATIONALE: The neonatal freeze lesion and adult partial cortical isolation ([dsquote]undercut[dsquote]) are models of epileptogenic microgyria and post-traumatic epileptogenesis, respectively. Results of field potential and neuronal recordings have shown that epileptiform activity occurs in [italic]in vitro[/italic] slices of both models. The expression of c-fos is known to be enhanced in regions of high neuronal activity, such as occur during epileptiform discharges. We hypothesized that chronic epileptiform activities occurring in vivo in neocortex of these lesional models would result in chronic elevations in c-fos immunoreactivity (IR).
METHODS: Immunocytochemical staining for the K-25 polyclonal c-fos antibody (Santa Cruz Biotechnology) was performed in coronal sections (35 [mu]M) from freeze-lesioned, undercut, and na[iuml]ve littermate control rats. Lesions were made as previously described, and all animals were perfused with 4% paraformaldehyde. Freeze lesions were made within 48 hours of birth and perfused between 30 and 40 days postnatally (P). Undercuts were made at P21 and perfused 3-4 weeks after the lesion.
RESULTS: Our results in control animals confirmed previous findings (Herdegen et al 1993 JCN,333:271.): there was little c-fos IR within neocortex, except within a few scattered cells in layer II/III and some layer VI cells. In the undercut model, the intensity of cellular c-fos IR was enhanced in layers II-VI within the undercut region, and particularly along the transcortical lesion. In freeze-lesioned cortex, both cellular and neuropil c-fos labeling were enhanced within the microgyrus and in superficial layers, extending several millimeters (mm) away from the sulcus. Cellular and prominent dendritic labeling was also increased in layer V adjacent to the microgyrus. In both models, the c-fos enhancement extended for several mm adjacent to the lesioned area. Neocortex contralateral to both undercuts and freeze lesions was similar to control neocortex in both level and pattern of c-fos IR.
CONCLUSIONS: Results suggest that lesions in both neonates and adult animals produce a long-lasting increase in neuronal activities within both the lesioned area and adjacent neocortical regions. Chronic increases in the expression of this immediate early gene may contribute to the substantial reorganization within the injured cortex that leads to epileptogenesis. These results further suggest that these animals may have either subclinical or behavioral seizures that have not yet been observed.
Support: NIH grant NS12151 from the NINDS.