Behavioural and histopathological assessment of the effects of periodic fasting on pentylenetetrazol-induced seizures in rats.

OBJECTIVES: Periodic fasting (PF) was suggested to display antiepileptic and neuroprotective effects, which is in stark contrast to severe fasting or starvation. However, these beneficial effects seem to depend on the type and duration of the used feeding protocol. There are discrepancies concerning both antiepileptic and neuroprotective effects of a PF-diet during repetitive seizures in different epilepsy models. This study was designed to evaluate the effects of different PF protocols on behavioural and histopathological consequences of epilepsy in adult rats. METHODS: Recurrent generalized seizures were caused by repetitive injection of pentylenetetrazol (PTZ) for a period of 4 weeks every other day. While control animals had free access to food and water, animals on a PF-diet were on intermittent fasting for 24 hours every 48 hours for 4 weeks before (T1), after (T2), or both before and after (T3) the injection of PTZ. Behavioural studies were carried out after PTZ injections and histological investigations were performed after the experiments were completed. RESULTS: Seizure assessment showed that the severity of seizures was significantly decreased in groups T1 and T3 when compared with control rats. Dark neuron densities in hippocampal CA1 and CA3 areas were decreased in PF groups, but never in the temporal cortex. The PF-diet also decreased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling-positive neurons in the hippocampus in both areas and all PF-diet protocols. DISCUSSION: These results support the idea that a PF-diet has anticonvulsive and neuroprotective effects on epileptic rats but underlines that different PF-diet protocols can have varying effects. Anticonvulsive effects were strongest when the PF-diet started before the onset of excitotoxic injuries, the number of dark neurons was decreased and apoptosis was prevented by all PF-diet protocols investigated in this work. Further evaluation of PF-diet protocols for possible clinical anticonvulsant and neuroprotective effects is suggested.

Bumetanide reduces seizure frequency in patients with temporal lobe epilepsy.

Alterations in the balance of K-Na-2Cl cotransporter (NKCC1) and Na-Cl cotransporter (KCC2) activity may cause depolarizing effect of γ-aminobutyric Acid (GABA), and contribute to epileptogenesis in human temporal lobe epilepsy. NKCC1 facilitates accumulation of chloride inside neurons and favors depolarizing responses to GABA. In the current pilot study we provide the first documented look at efficacy of bumetanide, a specific NKCC1 antagonist, on reduction of seizure frequency in adult patients with temporal lobe epilepsy. According to our results, seizure frequency was reduced considerably in these patients. Furthermore, epileptiform discharges decreased in two of our patients. If the efficacy of bumetanide is proven in large scale studies, it can be used as a supplemental therapy in temporal lobe epilepsy.

Using Poisson marginal models for investigating the effect of factors on interictal epileptiform discharge in patients with epilepsy.

BACKGROUND: Epilepsy is a common, chronic neurological disorder that affects more than 40 million people worldwide. Epilepsy is characterized by interictal and ictal functional disturbances. The presence of interictal epileptiform discharges (IEDs) can help to confirm a clinical diagnosis of epilepsy, and their location and characteristics can help to identify the epileptogenic zone or suggest a particular epilepsy syndrome. The aim of this study is to determine the factors that affect IEDs. MATERIALS AND METHODS: Poisson marginal model was done on 60 epileptic patients who were referred to Shefa Neurological Research Center, Tehran, for Video-Electroencephalogram (V-EEG) monitoring from 2007 to 2011. The frequency of IEDs was assessed by visual analysis of interictal EEG samples for 2 h. RESULTS: The results show that among age, epilepsy duration, gender, seizure frequency and two common anti-epileptic drugs (Valproic acid and Carbamazepine), only age and epilepsy duration had statistical significant effect on IED frequency. CONCLUSION: Investigating the factors affecting IED is not only of theoretical importance, but may also have clinical relevance as understanding the evolution of interictal epileptogenesis may lead to the development of therapeutic interventions. Generalized estimating equation is a valid statistical technique for studying factors that affect on IED. This research demonstrates epilepsy duration has positive and age has negative effect on IED which means that IED increases with epilepsy duration and decreases with increasing age. So for monitoring IED, we should consider both age and epilepsy duration of each patient.