E. Aronica et al., Cystatin C, a cysteine protease inhibitor, is persistently up-regulated inneurons and glia in a rat model for mesial temporal lobe epilepsy, EUR J NEURO, 14(9), 2001, pp. 1485-1491
Cystatin C (CSTC), a cysteine protease inhibitor, has been implicated in th
e processes of neuronal degeneration and repair of the nervous system. Usin
g serial analysis of gene expression (SAGE), we recently identified CSTC as
one of the genes that are overexpressed after electrically induced status
epilepticus (SE). In the present study, Western blot analysis extended the
SAGE results, showing increased CSTC protein in the hippocampus and entorhi
nal cortex. Immunocytochemistry revealed an increase in CSTC expression in
glial cells, which was first apparent 24 h after onset of SE, and persisted
for at least 3 months. Double immunolabelling confirmed that both reactive
astrocytes, and activated microglia were CSTC immunopositive. Within the h
ippocampus, up-regulation was also observed in neuronal cells within one da
y after SE. Up-regulation was still present in hippocampal pyramidal cells
and surviving interneurons of chronic epileptic rats (3-8 months post-SE).
This study demonstrates that status epilepticus leads to a widespread and p
ersistent up-regulation of CSTC in the hippocampus and entorhinal cortex, w
hich may represent an intrinsic neuroprotective mechanism in the course of
epileptogenesis that may counteract progression of the disease.