The Regulating Effect Of Nitric Oxide On Epilepsy

Nitric oxide (NO) is a secondary messenger which plays a very important and complicated role in regulating the onset and progress of epilepsy. However, different researchers made conflicted conclusions. Thus the function of NO was still left undetermined. Methodologically, we, for the first time, established a novel method in dynamically monitoring real-time intracellular neuron nitric oxide (NO) production with the aid of laser scanning confocal microscopy and fluorescence labeling technique. The method was highly sensitive, accurate and specific. The method was then further proved to be reliable and practicable in the evaluation of NO production in a penicillin 0 (PG)-induced neuron excitation model in vitro. Meanwhile, we, again for the first time, found two completely different dynamic models of NO production under PG stimulation (at series of concentrations). Next, the physiological significance of the two dynamic models was investigated. Based on the fact that the intercellular glutamate level and the integral state of cellular excitability (the proportion of active potential positive neurons) were positively co-related, the intercellular glutamate level was used to study the relation between NO and cellular excitability. As a result, we found that NO produced in a slow and late way tended to inhibit neuron excitation; while NO produced in a rapid and early way tended to promote neuron excitation. Finally, the molecular basis of NO in regulating cellular excitability was investigated. NO was found to inhibit neuron excitation by inhibiting methionine enkephalin (M-ENK) level and to promote neuron excitation by increasing M-ENK level and decreasing dynorphin-B (DYN-B) level. We also intended to discover whether NO could modulate M-ENK and DYN-B level by affecting the density of NMDA receptor (a subtype of Olu receptor). However, the result was negative. In all, this research introduced a new platform for related drug screening and pointed a new direction in the further research of epilepsy.