OBJECTIVETo investigate the antiepileptic effects of various stimulation modes of low-frequency stimulation(LFS) on the kindling rats.

METHODSStimulating electrodes were implanted in the amygdala and current with constant intensity was applied to evoke kindling-induced seizures. The antiepileptic effect of LFS by open loop stimulation(before kindling), closed loop stimulation(immediately after kindling) and different forms of closed loop stimulation(whole stage after kindling and early stage after kindling) were investigated in amygdala kindled rats.

RESULTSThe closed loop LFS of whole stage after kindling can significantly inhibited seizure stages(P<0.01) and reduced afterdischarge duration(P<0.05). The closed loop LFS of early stage after kindling can significantly suppress the seizure stages, mainly in stages 0-3(P<0.05 or P<0.01). The open loop low-frequency stimulation did not inhibit the seizure stage during kindling acquisition(P>0.05).

CONCLUSIONThe antiepileptic effect of low frequency stimulation may have a mode-dependent effect. It may be helpful for the deep brain stimulation as a promising approach applied to clinical antiepileptic therapy in the future.

Amygdala ; Animals ; Deep Brain Stimulation ; Kindling, Neurologic ; Rats ; Seizures ; therapy

OBJECTIVETo investigate whether the waveform of electrical stimulus affects the antiepileptic effect of focal low-frequency stimulation (LFS).

METHODSThe antiepileptic effects of the LFS in sine, monophase square and biphase square waves were investigated in hippocampal kindled mice, respectively.

RESULTSCompared to the control group, sine wave focal LFS (30 s) inhibited seizure stages (2.85 ± 0.27 vs 4.75 ± 0.12, P<0.05), lowered incidence of generalized seizures (53.6% vs 96.5%, P<0.01) and reduced afterdischarge durations [(16.2 2 ± 1.69)s vs (30.29 ± 1.12)s, P<0.01] in hippocampal kindled mice, while monophase or biphase square wave LFS (30 s) showed no antiepileptic effect. Monophase square LFS (15 min) inhibited seizure stages (3.58 ± 0.16, P<0.05) and incidence of generalized seizures (66.7%,P<0.01), but had weaker inhibitory effect on hippocampal afterdischarge durations than sine wave LFS. In addition, pre-treatment and 3 s but not 10 s post-treatment with sine wave LFS resulted in suppression of evoked seizures (P<0.05 or P<0.01).

CONCLUSIONThe antiepileptic effect of LFS is dependent on its waveform. Sine wave may be optimal for closed-loop LFS treatment of epilepsy.

Animals ; Anticonvulsants ; Electric Stimulation ; Epilepsy ; Hippocampus ; physiopathology ; Kindling, Neurologic ; Mice ; Seizures ; physiopathology

Amygdala ; Animals ; Disease Models, Animal ; Electroencephalography ; Epilepsy ; etiology ; physiopathology ; Kindling, Neurologic ; Male ; Rats ; Rats, Wistar

OBJECTIVETo investigate the effects of epileptogenesis and low frequency stimulation at epileptic focus on spontaneous neuropathic pain in rats.

METHODSBipolar stimulating electrodes were implanted in the amygdala and current with constant intensity was applied to evoke kindling-induced seizures. In partial and generalized stages of seizure acquisition, neuroma model of spontaneous neuropathic pain was prepared by completely transection of the left sciatic and saphenous nerves of rats. Autotomy behavior was scored daily until d 63 postoperatively. Rats were divided into 5 groups: Control (n=7), rats with partial seizures (1-3 stages, n=5), rats with generalized seizures (4-5 stages, n=7), rats with partial seizures and low frequency stimulation(n=4), rats with generalized seizures and low frequency stimulation(n=4). Low frequency stimulation was applied to the amygdala, the epileptic focus for 21 d from the d 2 after nerve transection.

RESULTSAutotomy level in rats with partial seizures was significantly lower than that in controls. The autotomy scores during postoperative d 40 ≊63 were significantly lower than those of controls, the area under the progression curve of autotomy behavior was decreased from 308.2 ±51.57 to 45.80 ±24.64, the onset day of autotomy was postponed by 32 d and none of the animals with partial seizures showed high autotomy, while 71.4 % of controls showed that on d 63 postoperatively. Rats with generalized seizures showed autotomy similar to controls, except that the onset day was postponed by 16 d. Autotomy behavior in rats receiving low frequency stimulation of the amygdala was not different from that in controls.

CONCLUSIONFocal seizures can lower sensitivity to spontaneous neuropathic pain in rats, while low frequency stimulation applied to the focus can abolish such effect.

Animals ; Disease Models, Animal ; Electric Stimulation ; adverse effects ; Epilepsy ; complications ; etiology ; Kindling, Neurologic ; Male ; Neuralgia ; etiology ; Rats ; Rats, Sprague-Dawley

AIMThe electrographic and behavioral kindling effects were induced by chronic tetanization of the right caudate-putamen (CPu) to study the target-behavior expression involved in the CPu or hippocampus (HPC) network abnormalities.

METHODSExperiments were performed on 58 SD rats. Tetanization (60Hz,0.4 - 0.6mA, 2s) was delivered into the CPu or the HPC, once a day, for 7-12 days. Animal behaviors were observed every day and depth electrographs were recorded at the beginning or at the end of the experiments.

RESULTSChronic tetanization of the CPu or of the HPC induced: (1) Rhythmic sharp waves in the CPu and paroxysmal epileptiform events in the HPC electrographs. (2) Primary behavioral seizures, secondary behavioral seizures, and kindling effects, including wet dog shakes (WEDS), rearing, face washing, immobility, chewing and head nodding. (3) Lower rate of primary WEDS (P < 0.01), and higher rate of secondary WEDS (P < 0.01) in the CPu-tetanized rats. (4) Longer silent period of behavioral seizures before kindling appeared in the CPu-tetanized rats.

CONCLUSIONKindling effects in the CPu-tetanized rats resembles those in the HPC-tetanized rats. The CPu might participate in the origin of epileptic focus and be involved in reestablishment of limbic epileptic networks, which may be responsible for the target-behavioral seizures.

Animals ; Behavior, Animal ; Caudate Nucleus ; Electric Stimulation ; Epilepsy ; physiopathology ; Kindling, Neurologic ; Male ; Rats ; Rats, Sprague-Dawley ; Seizures ; physiopathology

Animals ; Kindling, Neurologic ; drug effects ; Male ; Pentylenetetrazole ; toxicity ; Rats ; Rats, Wistar ; Skin ; innervation ; Sympathetic Nervous System ; physiology

BACKGROUNDCurcumin can reduce the severity of seizures induced by kainate acid (KA), but the role of curcumin in amygdaloid kindled models is still unknown. This study aimed to explore the effect of curcumin on the development of kindling in amygdaloid kindled rats.

METHODSWith an amygdaloid kindled Sprague-Dawley (SD) rat model and an electrophysiological method, different doses of curcumin (10 mgxkg(-1)xd(-1) and 30 mgxkg(-1)xd(-1) as low dose groups, 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1) as high dose groups) were administrated intraperitoneally during the whole kindling days, by comparison with the course of kindling, afterdischarge (AD) thresholds and the number of ADs to reach the stages of class I to V seizures in the rats between control and experimental groups. One-way or two-way ANOVA and Fisher's least significant difference post hoc test were used for statistical analyses.

RESULTSCurcumin (both 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1)) significantly inhibited the behavioral seizure development in the (19.80 +/- 2.25) and (21.70 +/- 2.21) stimulations respectively required to reach the kindled state. Rats treated with 100 mgxkg(-1)xd(-1) curcumin 30 minutes before kindling stimulation showed an obvious increase in the stimulation current intensity required to evoke AD from (703.3 +/- 85.9) microA to (960.0 +/- 116.5) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin showed a significant increase in the stimulation current intensity required to evoke AD from (735.0 +/- 65.2) microA to (867.0 +/- 93.4) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class both IV (as (199.83 +/- 12.47) seconds) and V seizures (as (210.66 +/- 10.68) seconds). Rats treated with 100 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class V seizures (as (219.56 +/- 18.24) seconds).

CONCLUSIONOur study suggests that curcumin has a potential antiepileptogenic effect on kindling-induced epileptogenesis.

Amygdala ; physiopathology ; Animals ; Anticonvulsants ; pharmacology ; Curcumin ; pharmacology ; Kindling, Neurologic ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Seizures

OBJECTIVETo investigate the effects of antisense glutamic acid decarboxylase (GAD(67)) oligodeoxynucleo-tide (ODN) on behavior, seizure threshold and EEG of hippocampus in the epileptic rats induced by pentylenetetrazol (PTZ).

METHODSA model of chronic epilepsy in rats was established by PTZ. The inhibition of GAD(67) mRNA expression in hippocampus was selectively induced by antisense oligodeoxynucleotide of GAD(67). The effect of antisense GAD(67) ODN on behavior, seizure threshold and EEG recording of kindled rats was examined.

RESULTSAntisense GAD(67) ODN could inhibit the expression of GAD(67) mRNA and the concentration of GABA. It also could significantly shorten the latencies of seizure and increase the level of seizure and the frequency of epileptiform discharges.

CONCLUSIONThe gene of GAD(67) may be an anti-seizure gene, which might inhibit epileptiform discharge. The treatment of epilepsy by GAD(67) gene will have a bright future.

Animals ; Electroencephalography ; Epilepsy ; chemically induced ; physiopathology ; Glutamate Decarboxylase ; genetics ; pharmacology ; Hippocampus ; physiopathology ; Isoenzymes ; genetics ; pharmacology ; Kindling, Neurologic ; Male ; Oligonucleotides, Antisense ; pharmacology ; Pentylenetetrazole ; Rats ; gamma-Aminobutyric Acid ; analysis

OBJECTIVETo observe the dynamics of hippocampal release of glutamate (Glu) and gamma-aminobutyric acid (GABA) in epilepsy (TLE) after administration with high frequency stimulation (HFS).

METHODSThe SD were divided into four groups (n =10): (1) Control group (KB) the rats were injected intraperitoneally with saline 0.9%. (2) Kainic acid (KA) group: the rats were injected with KA. (3) Pseudo-deep brain stimulation (DBS) group: the KA-induced rats were implanted with rheophores alone. (4) DBS group: KA induced-rats with DBS in hippocampal epileptic foci. We then collected hippocampal extracellular fluid by microdialysis and the levels of Glu and GABA were measured by high-performance liquid chromatography (HPLC) and fluorescence detection.

RESULTSThere was no difference in the baseline of Glu and GABA in the four groups. In contrast, a significant increase in the content of Glu and GABA was shown in the three periods of KA-kindled seizures. Electrical stimulation of hippocampus resulted in a decrease of hippocampal Glu contents, while there was no change in GABA contents. Additionally, HFS of hippocampus normalized the Glu/GABA ratio in the chronic period of seizures.

CONCLUSIONThe high frequency stimulation of epileptic foci may protect against seizures by modulating the extracellular release of hippocampal Glu.

Animals ; Electric Stimulation ; methods ; Epilepsy ; chemically induced ; therapy ; Glutamic Acid ; secretion ; Hippocampus ; metabolism ; Kainic Acid ; Kindling, Neurologic ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; gamma-Aminobutyric Acid ; secretion

OBJECTIVETo investigate effect of chronic transauricular kindled seizures on passive-avoidance test memory retention in rats.

METHODSChronic transauricular kindled seizures was induced by repeated application of initially subconvulsive electrical stimulation through ear-clip electrodes once every 24 h until the occurrence of 3 consecutive clonic-tonic seizures. A passive avoidance test was used to measure memory retention ability. Morphological changes in neurons of hippocampal CA1 region was examined after HE staining. Histamine, gamma-aminobutyric acid (GABA) and glutamate levels in the hippocampus were measured by high performance liquid chromatography (HPLC).

RESULTChronic transauricular kindled seizures impaired passive-avoidance test memory retention in rats. The damaged CA1 neurons were observed and histamine content in the hippocampus markedly decreased 24 h after the end of kindling in the chronic transauricular kindled rats.

CONCLUSIONChronic transauricular kindled seizure impaired passive-avoidance test memory retention, and it might be due to the damaged CA1 neurons and a decrease of histamine in the hippocampus induced by epilepsy.

Animals ; Avoidance Learning ; Hippocampus ; metabolism ; pathology ; physiopathology ; Histamine ; metabolism ; Kindling, Neurologic ; Male ; Memory Disorders ; etiology ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Seizures ; metabolism ; pathology ; physiopathology ; gamma-Aminobutyric Acid ; metabolism