Abstract:OBJECTIVE: The effects of nuclear factor-kappaB (NF-κB) on neurons in the brain remain controversial. This study examined the relationship between NF-κB activation and neuronal apoptosis in rats with pentylenetetrazol (PTZ)-induced serious seizures. METHODS: Forty-two rats were randomly assigned into a Seizure group, a pyrrolidine dithiocarbamate (PDTC)-pretreatment seizure group and a Normal control group. The model of serious seizures was induced by an intraperitoneal injection of PTZ (60 mg/kg). Rats in the Seizure group were sacrificed 3, 6, 12, 24, and 48 hrs after seizure induction. The PDTC pretreatment group was administered with PDTC (100 mg/kg) 1 hr before PTZ injection, and sacrificed 24 hrs later. The immunohistochemistry method was used to detect the activity of NF-κB protein in the CA1 region of the hippocampus. The in situ dUTP end-labeling (TUNEL) technique and flow cytometry (FCM) were used to measure the neuronal apoptosis in the hippocampus. RESULTS: Significant neuronal apoptosis was observed in the Seizure group and peaked at 24 hrs, with an apoptosis rate of 12.54%±4.99%, compared with (2.24%±0.57%) in the Normal control group (P<0.001). The activity of NF-κB was detected at 6 hrs following seizure induction, and increased to maximal expression at 24 hrs (32.30±4.71/gcs)in the Seizure group. NF-κB activation was not found in the Normal control group. The PDTC pretreatment group showed a lower neuronal apoptosis rate and less NF-κB activity than the Seizure group. CONCLUSIONS: The activation of NF-κB may play important roles in the process of neuronal apoptosis following serious seizures. PDTC pretreatment could reduce the neuronal apoptosis, perhaps by inhibiting the expression of NF-κB.
