Upregulation of cystatin C expression in the rat hippocampus during epileptogenesis in the amygdala stimulation model of temporal lobe epilepsy.

Cystatin C is a cysteine proteinase inhibitor with widespread distribution in body fluids and tissues, abundant in the cerebrospinal fluid and in brain tissue. There is an implied role for cystatin C in several neurologic disorders, but the actual function of cystatin C in the brain remains unknown. Moreover, the reports on the distribution of cystatin C in the brain are controversial. We present the data on the distribution of cystatin C in normal brain tissue and during epileptogenesis. Epileptogenesis was triggered by inducing self-sustained status epilepticus (SSSE) with a 20- to 30-min electrical stimulation of the amygdala in rats. Animals were monitored continuously for 2 weeks with video-EEG to ascertain that they were in an epileptogenic phase. Analysis of double-stained immunopreparations indicated that in normal brain, cystatin C is expressed mainly in microglia. In epileptogenic animals, immunostaining was increased in the microglia as well as in the neuropil at 4 days, 1 week, and 2 weeks after SSSE. Moreover, the density of cystatin C-positive microglia was associated with the severity of neuronal damage in the CA1 subfield of the hippocampus. This is the first report linking cystatin C with epileptogenesis and epilepsy. Further studies will explore the potential neuroprotective functions of this protein during epileptogenesis and whether the manipulation of its expression or function will have therapeutic implications.