Anticonvulsive and antioxidant effects of curcumin on pilocarpine-induced seizures in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Curcumin, an active ingredient of turmeric with antioxidant and anti-inflammatory properties has recently been reported to have anticonvulsant effects in several animal models of epilepsy. This study aimed to investigate the effects of curcumin on the pilocarpine rat model of status epilepticus.</p><p><b>METHODS</b>The effect of intraperitoneal administration of curcumin (30, 100, and 300 mg/kg) on pilocarpine-induced seizures in rats was tested. The correlation between seizure activity and hippocampal levels of nitric oxide synthase and free radicals was quantified. Whether curcumin treatment modulated these parameters was also investigated.</p><p><b>RESULTS</b>Curcumin significantly increased seizure threshold at doses of 100 and 300 mg/kg. Rats with pilocarpine- induced seizures showed significantly elevated levels of malonaldehyde, nitric oxide synthase, and lactate dehydrogenase, but decreased levels of superoxide dismutase and glutathione compared with normal control rats. At doses of 100 and 300 mg/kg, curcumin reversed the effects of pilocarpine-induced seizures on nitric oxide synthase, lactate dehydrogenase, glutathione, and superoxide dismutase. However, curcumin did not restore the elevated malonaldehyde levels.</p><p><b>CONCLUSION</b>Curcumin has anticonvulsant activity in the pilocarpine rat model of seizures, and that modulation of free radicals and nitric oxide synthase may be involved in this effect.</p>

Dynamic changes of estradiol and pregnenolone levels in serum and hippocampus of female rats with epilepsy / 中华神经医学杂志

Objective To observe the dynamic changes of estradiol(E2)and pregnenolone (PREG)levels in serum and hippocampus of female rats with epilepsy and explore the relationship between E2 level in the hippocampus and severity of seizure. Methods The seizure model was established by injecting kainite(KA)into the hippocampus of amygdala-kindled rats.The behaviors at the moment of epileptic seizure were observed and serum and hippocampus samples were collected at 0,1,2,3,4,5,6,12 and 24 h after seizure.Rats in the control group was injected the same volume of saline at the sanle time points.The levels of E2 and PREG in the Seizure and control groups were measured by radioimmunoassay and enzyme linked immunosorbent assay,respectively.These results were statistically analyzed. Results Epileptic Seizure was showed after KA injection 5 to 10 min with the strongest seizure appearing at 3 h.The level of E2 was not significantly different in serum of the rats with epileptic seizure.While the level of E2 significantly changed in the hippocampal tissue after seizure:it elevated 1h after epileptic seizure,peaked at 4 h and returned to normal at 12 h;statistically significant differences of E2 level in the hippocampai tissue was showed among different time points(P<0.05).Besides,the E2 level in the hippocampus was increased gradually with the aggravation of the seizure(R~2=0.646,P<0.05).No significant differences were found in the PREG level of the hippocampal tissues between the rats treated with KA and the rats in the control group. Conclusion Epileptic seizure can induce local E2 synthesis in the rat hippocampus,thus,the E2 level in the hippocampus and severity of seizure is positively correlative.

Curcumin inhibits amygdaloid kindled seizures in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Curcumin 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.</p><p><b>METHODS</b>With 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.</p><p><b>RESULTS</b>Curcumin (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).</p><p><b>CONCLUSION</b>Our study suggests that curcumin has a potential antiepileptogenic effect on kindling-induced epileptogenesis.</p>

Effect of curcumin on AMPA and kainate receptor-mediated calcium influx in cultured rat hippocampal neurons / 中华神经医学杂志

Objective To investigate the effect of curcumin on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) receptor-mediated calcium influx in cultured rat hippocampal neurons. Methods The hippocampal neurons from SD rat embryos (17 days old) were cultured for 9 days, and fluorescent calcium chelator and confocal microscopy calcium imaging were used to observe the changes in intracellular free calcium in the neurons following stimulation with 100 μmol/L KA. The effect of curcumin pretreatment at different concentrations (10, 30, 50, 100, 200 and 300 μmol/L) for 30 min on 100 μmol/L KA-induced intracellular calcium changes in the neurons were evaluated, and the effect of 15 μmol/L curcumin on intracellular calcium in the neurons stimulated with 10, 30, 50, 100, 200 and 300 μmol/L KA were also assessed. Cobalt staining was used to examine the expression of calcium permeable AMPA/KA channel in the hippocampal neurons treated with 30 and 100 μmol/L KA. Results Curcumin pretreatment at different concentrations for 30 min significantly relieved the elevation of flee calcium concentration induced by 100 or 30 μmol/L KA (P<0.05), and the effect was especially obvious with 15 μmol/L KA curcumin. Both 30 and 100 μmol/L KA increased the ratio of cobalt staining-positive hippocampal neurons, and curcumin pretreatment at 15 μmol/L, but not at 5 or 30 μmol/L, significantly reduced the ratio of the positive neurons (P<0.05). Conclusion Curcumin at appropriate concentrations can modulate calcium influx mediated by AMPA and KA in cultured rat hippocampal neurons, which might be one of the anti-epileptic mechanisms of curcumin