Neuroprotective effects of zonisamide on cerebral ischemia injury via inhibition of neuronal apoptosis

It is known that neuronal apoptosis contributes to pathology of cerebral ischemia injury. Zonisamide (ZNS) has shown anti-apoptosis effects in recent studies. The present study investigated whether the anti-apoptotic effect can account for the neuroprotective action of ZNS on cerebral ischemia. Neuronal cells were maintained under oxygen-glucose deprivation conditions to simulate cerebral ischemia and treated with ZNS simultaneously. The apoptosis of the cells and expression of apoptosis-related proteins were investigated by flow cytometry and western blot analysis, respectively. A cerebral ischemia mouse model was created via middle cerebral artery occlusion, and the mice were treated with ZNS. Neurological deficit scores and infarct volumes of the cerebral ischemia mice were measured. The apoptosis status of the neuronal cells was evaluated by TUNEL staining. In vitro, the ZNS treatment inhibited both the apoptosis of the neuronal cells and apoptosis-related protein expression (caspase-3, caspase-8, and calpain-1) induced by the oxygen-glucose deprivation. The anti-apoptosis effect of ZNS could occur through the blocking of reactive oxygen species. Moreover, ZNS treatment significantly ameliorated neurological deficits and reduced infarct volumes in the cerebral ischemia mice model. In this study, ZNS exerted neuroprotective effects by inhibition of apoptosis in neuronal cells in cerebral ischemia. Therefore, ZNS might be a promising therapy for cerebral ischemia.

Post marketing surveillance on the use of zonisamide for epilepsy in the Philippines: A preliminary report

The objective of the study is to monitor on a wide population base the safety and efficacy of zonisamide in patients with partial, generalized, and combined seizures. This is an open label, descriptive, post-marketing surveillance preliminary report that includes the data obtained from October 2008 to May 2010 of a four-year study. The study included 516 patients allocated to either zonisamide monotherapy or zonisamide add-on therapy, with efficacy and safety assessed monthly for three months. For adult patients, a maximum oral dose of 600 mg per day was allowed while a maximum dose of 12 mg/kg/day of zonisamide was allowed for pediatric patients. Efficacy measures were the proportion of responders and percentage change in seizure frequency from baseline. 321 of the 516 patients were included in the efficacy analysis. The responder rates were 53.27%, 80.37%, and 92.52% after the 1st month, 2nd month, and 3rd month of treatment respectively. The use of zonisamide led to seizure-reduction rates of 45.74%, 68.43%, & 82.85% during the 1st, 2nd, & 3rd month of use respectively. Safety analysis was done on all the 516 subjects. Adverse events were mostly mild and observed in 6.78% of patients. No serious adverse events were encountered. 7 subjects (1.4%) discontinued taking zonisamide because of increased seizure frequency in 4 patients, and 1 patient each due to absence of effect on seizure-control, rashes, and thrombocytopenia. All the rest continued taking zonisamide.