Systemic administration of
kainic acid induces repeated convulsive
seizures (KA convulsions) that result in neuropathological changes similar to
temporal lobe epilepsy and the appearance of spontaneous recurrent
seizures (SRS). The appearance of SRS is considered a result of the remodeling of neuronal networks following neuronal degeneration. We investigated the changes in
chondroitin sulfate proteoglycans (CSPGs) in the limbic structures after KA convulsions in the rat using
monoclonal antibodies 1G2, which recognizes full-length
neurocan and the C-terminal half of
neurocan,
neurocan C, and 6B4, which recognize
phosphacan and
protein tyrosine phosphatase zeta. After KA convulsions, full-length
neurocan appeared by 24 h and reached a peak by 48 to 72 h, whereas
phosphacan decreased within 24 h in the hippocampus. In immunohistochemistry,
neurocan increased in the limbic structures coincident with the appearance of reactive astrocytes.
Phosphacan decreased coincident with pyramidal cell loss in the hippocampus, and the number of
phosphacan-positive perineuronal nets around
parvalbumin neurons decreased, whereas
parvalbumin neurons were relatively conserved. In contrast,
phosphacan increased in the entorhinal and piriform cortices in correlation with the severity of neuronal loss. Both
neurocan and
phosphacan recovered to the control level by 8 weeks after KA convulsions in some rats, but the changes in
neurocan and
phosphacan described above still persisted in more than half the rats. The results indicate that KA convulsions induce prolonged changes in
neurocan and
phosphacan similar to those in the developing rat brain and suggest a role of these CSPGs in the remodeling of neuronal networks related to the establishment or enhancement of epileptogenesis.