| Epilepsy is a serious chronic neurological disease, which is characterized by recurrent abnormal discharge of cerebral neurons and transient disfunction of brain. The clinical symptoms include a variety of abnormities in motor, sense, conscious state, vegetative nervous and psychology. According to WHO, 50 million persons worldwide, and 8 million in China have suffered from the diseases. The exact pathogenesis of epilepsy remains largely unclear. Excessive excitability, over-synchronized discharges and the imbalance between excitation and inhibition of cerebral neurons may contribute to seizures. With the currently available antiepileptic drugs, the disease in about 80% patients who have no serious injuries in the brain, especially those with fewer frequencies of seizures and normal interictal EEGs, are well controlled. By contrast, about 25% epileptic patients can't get effective therapies using those drugs. This epilepsy is called drug-resistance or intractable epilepsy. Moreover, long application of those antiepileptic drugs often results in some adverse responses in psychological, neurological, splanchnic and skin system. Thus, developing new safe and effective antiepileptic methods is urgently expected.With the widely application of deep brain stimulation (DBS) in the treatment of motor disorder diseases, the roles of DBS in drug-resistance epilepsy become more and more important. So far, about 5000 epilepsy patients have received DBStreatment and the frequency and severity of epileptic attack among them were well-controlled. However, the fundamental questions of where to stimulate and what types of stimuli are most effective remain unclear. So our experiment was designed to observe the possible role of stimulation parameter (frequency) and stimulation targets (central piriform cortex and tuberomammillary nucleus E2 region) in kindling model of epilepsy, and expected to provide further evidence of DBS in the clinic.1. Low-frequency stimulation of central piriform cortex inhibits amygdaloid-kindled seizures and epileptic focus transfer in Sprague-Dawley rats Aim: The central piriform cortex (cPC) is considered to be critically involved in the generation and propagation of kindled seizures. Our previous study found that low-frequency stimulation (LFS) of the cPC inhibits the development process of amygdala kindling. In this study, we determined whether unilateral LFS of the cPC had an inhibitory effect on amygdaloid-kindled seizures and epileptic focus transfer in Sprague-Dawley rats. Methods: 1. When fully-kindled seizures were achieved by daily amygdala electrical stimulation (2 s train of 1 ms pulses at 60 Hz and 150-300 μA), LFS (15 min train of 0.1 ms pulses at 1 Hz and 50-150μA) was applied to the ipsilateral or contralateral cPC 1 s after cessation of kindling stimulation for 10 days.2. The ipsilateral cPC received LFS immediately 1 s after termination of once daily kindling stimulation in the right amygdala (primary site) until all animals reached kindled state. Then, left amygdala (secondary site) afterdischarge threshold and kindling rate were measured at different stages of primary site kindling. Results: 1. LFS of the ipsilateral cPC significantly decreased the incidence of generalized seizures and seizure stage, and shortened cumulative afterdischarge duration and cumulative generalized seizure duration. LFS of the contralateral cPC also significantly decreased the expression of seizure stage, but had no appreciable effect on the generalized seizure incidence, cumulative afterdischarge duration and cumulative generalized seizure duration. On the other hand, LFS of the ipsilateral cPC significantly increased the afterdischarge threshold and further increased the differences of current intensity between afterdischarge threshold and generalizedseizure threshold. 2. In the case of primary site reached kindled state (stage 5), the decrement of afterdischarge threshold at secondary site after LFS was fewer than control animals, and the number of days for this site reached kindled state also significantly increased; In the case that primary site did not reach kindled state (stage 1-4), there were no apparent differences of secondary site afterdischarge threshold and kindling rate between LFS and control groups. Conclusion: Our data suggest that LFS of the cPC may be an effective method of inhibiting kindled seizures by preventing both afterdischarge generation and propagation, and LFS also have an inhibitory effect on epileptic focus transfer in Sprague-Dawley rats. It provide further evidence that brain regions like the cPC, other than the seizure focus, can serve as targets for deep brain stimulation treatment of epilepsy.2. Unilateral low-frequency stimulation of histaminergic tuberomammillary nucleus ￡2 region facilitates basolateral amygdaloid-kindling in ratsAim: The tuberomammillary nucleus (TM), located in the posterior hypothalamus, is the sole seat of histaminergic neurons in the brain. In this study, we investigate whether low-frequency stimulation (LFS) of TM E2 region is involved in the acquisition of amygdaloid-kindling seizures. Methods: The ipsilateral or contralateral TM E2 region received LFS (15 min train of 0.1 ms pulses at 1 Hz and 300-400 μA) immediately 1 s after termination of once daily kindling stimulation (2 s train of 1 ms pulses at 60 Hz and 150-300 μA) in the right amygdala for twenty days. Results: LFS of either ipsilateral or contralateral TM E2 region significantly facilitated the progression of seizure stages and increased afterdischarge duration throughout the course of amygdaloid kindling. The marked facilitation induced by LFS on either side of the TM was predominantly due to the significant promotion of progression from stage 3 to stage 5 seizures. Conclusion: The significant facilitative effect of LFS on TM strongly indicated that the role of LFS in epilepsy is brain region specific and possibly another unknown mechanism that underlie classic explanation of LFS may be involved in this action.
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