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

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

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

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 study the effect of maternal isolation stress on the epilepsy susceptibility in young rats and the possible mechanism.

METHODSSixty Sprague-Dawley young rats were randomly divided into a normal control and two maternal isolation groups that were subjected to maternal isolation for 15 min or 3 hrs daily on postnatal days 2-17. On postnatal day 18, an amygdala kindling test was performed to induce seizures. The expression of GABA(A) receptor α₁ in the hippocampus was determined by immunohistochemisty.

RESULTSThe weights were reduced, the threshold of amygdala kindling and the stimulation number for full kindling decreased significantly, and seizures were more severe in the maternal isolation 3 hrs group compared with the normal control group. The expression of GABA(A) receptor alpha(1) in the hippocampus CA1 area in the maternal isolation 3 hrs group decreased significantly compared with that in the normal groups. There were no significant differences in the aspects above mentioned between the maternal isolation 15 min and normal control groups.

CONCLUSIONSThe stress of early daily maternal isolation for 3 hrs may affect adversely brain development and increase epilepsy susceptibility in young rats. The decreased expression of GABA(A) receptor α₁ in the hippocampus may contribute to the potential mechanism.

Amygdala ; physiology ; Animals ; Disease Susceptibility ; Epilepsy ; etiology ; Female ; Hippocampus ; chemistry ; Kindling, Neurologic ; Maternal Deprivation ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A ; analysis ; Stress, Psychological ; complications

OBJECTIVETo investigate and compare the effects of Compound Chaihu Shugan Decoction (CHSGD, "treatment from Gan") and Dingxian Pill (DXP, "treatment from the sputum") on the metabolism path of glutamate in the pentylenetetrazol-kindled seizure rats' hippocampus, thus exploring the molecular mechanism of "heterotherapy for homopathy".

METHODSA chronic kindling seizures rat model was established by intraperitoneal injecting pentylenetetrazol (PTZ). Totally 24 fully kindled seizure rats were randomized into four groups, i.e., the model control group, the Sodium Valproate (VPA) group, the DXP group, and the CHSGD group. They were respectively treated with normal saline, VPA, CHSGD, and DXP, respectively. Rats in the control group were treated with normal saline by peritoneal injection and by gastrogavage. After intragastric administration for 4 successive weeks, the glutamate (Glu) levels in the hippocampus were detected by high performance liquid chromatography (HPLC). The expressions of glutamate transporter-1 (GLT-1) proteins were detected by Western blot. The activity of glutamine synthetase (GS) was detected by using GS detection kit.

RESULTSCompared with the control group, the content of Glu in the model group significantly increased, and the expression of GLT-1 and the activity of GS significantly decreased (P < 0.01). Compared with the model group, the content of Glu in each medication group significantly decreased, and the protein expression of GLT-1 as well as the activity of GS significantly increased (P < 0.01). But when compared between the CHSGD group and the DXP group, the content of Glu was lower and the activity of GS was higher in the CHSGD group than in the DXP group (P < 0.01), while there was no statistical difference in the expression of GLT-1 between the two groups (P > 0.05).

CONCLUSIONSCHSGD ("treatment from Gan") and DXP ("treatment from the sputum") could both decrease the level of Glu and raise the expression of GLT-1 and the activity of GS, indicating that CHSGD and DXP both could regulate the metabolism path of Glu to affect the level of the Glu in the brain. But the effects of CHSGD were superior to those of DXP in decreasing the content of Glu and up-regulating the activity of GS, suggesting that there were some different effects targets between the two compounds on the metabolism path of Glu, which may be one of possible molecular mechanisms for treating epilepsy by heterotherapy for homopathy.

Animals ; Excitatory Amino Acid Transporter 2 ; metabolism ; Glutamic Acid ; metabolism ; Hippocampus ; metabolism ; Kindling, Neurologic ; Male ; Medicine, Chinese Traditional ; methods ; Pentylenetetrazole ; adverse effects ; Rats ; Rats, Wistar ; Seizures ; metabolism ; therapy

OBJECTIVETo investigate the effects and the mechanisms of the first-generation histamine H(1)-antagonist diphenhydramine and the second-generation histamine H(1)- antagonist fexofenadine on seizure development of pentylenetetrazole (PTZ)-induced kindling in rats.

METHODSThe first-or second-generation histamine H(1)-antagonists and/or histidine were ip injected in rats every 48 h, followed by a subconvulsive dose of PTZ (35 mg/kg). Then the behavioral changes were observed for 30 min after every injection of PTZ. The histamine content of brain was measured spectrofluorometrically.

RESULTCompared with the control group, diphenhydramine (5 mg/kg) significantly augmented the severity of seizure development of PTZ-induced kindling, whereas fexofenadine (5 mg/kg) had no marked influence. The effects of diphenhydramine were antagonized by histidine, the precursor of histamine.

CONCLUSIONSeizure development of PTZ-induced kindling is promoted by the first-but not the second generation histamine H(1)-antagonists via the blockade of brain histamine H(1)-receptor.

Animals ; Histamine ; physiology ; Histamine H1 Antagonists ; pharmacology ; Histamine H1 Antagonists, Non-Sedating ; pharmacology ; Histidine ; pharmacology ; Kindling, Neurologic ; drug effects ; Male ; Pentylenetetrazole ; Rats ; Rats, Sprague-Dawley ; Seizures ; chemically induced