Neuroprotective Effect of Vitamin E in a Kainate-Induced Rat Model of Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) is known as the most common form of epilepsy in adults and as the type most resistant to treatment. Neuroprotective treatments are considered as a promising therapy for preventing and treating TLE. We investigated the possible neuroprotective effect of vitamin E in an intrahippocampal kainate model of TLE in rats. Kainate injection caused a higher incidence rate of seizures, and vitamin E pretreatment significantly attenuated this index. Intrahippocampal kainate also led to elevation of the malondialdehyde and nitrite/ nitrate levels and lowered superoxide dismutase (SOD) activity, while vitamin E significantly restored MDA and SOD indices. In addition, intrahippocampal kainate induced a significant degeneration of neurons in the CA1, CA3, and hilar regions of the hippocampus; vitamin E considerably attenuated these changes. Timm staining data demonstrated mossy fiber sprouting (MFS) in the dentate gyrus of kainate-lesioned rats, and vitamin E significantly lowered the MFS intensity. Our data suggest that vitamin E pretreatment is capable of attenuating seizures and inhibiting hippocampal neuronal loss and MFS in the kainate-induced model of TLE. A part of the beneficial vitamin E effects is due to its potential to mitigate oxidative stress.«Скронева» епілепсія (СЕ) – найпоширеніша форма епілепсії у дорослих, причому найбільш резистентна до лікування. Як перспективний напрямок у профілактиці та лікуванні СЕ розглядаються підходи, засновані на нейропротекції. Ми досліджували можливий нейропротекторний ефект вітаміну Е на „каїнатній” моделі СЕ у щурів (інтрагіпокампальне введення каїнату). Такі ін’єкції зумовлювали підвищену ймовірність прояву судом, а попереднє курсове введення вітаміну Е істотно знижувало відповідний індекс. Ін’єкції каїнату також призводили до зростання рівнів малонового альдегіду та нітритів/нітратів і падіння активності супероксиддисмутази; під впливом вітаміну Е відповідні значення нормалізувалися. До того ж, інтрагіпокампальні введення каїнату викликали істотну дегенерацію нейронів у зонах CA1 та CA3 і хілусі гіпокампа, а вітамін Е значно обмежував ці зміни. Результати забарвлення за Тіммом продемонстрували наявність феномену спраутинга моховитих волокон у зубчастій звивині щурів після введення каїнату; вітамін Е істотно зменшував інтенсивність даного процесу. Наші результати дозволяють нам вважати, що попередня дія вітаміну Е сприяє зменшенню інтенсивності судом, знижує загибель нейронів у гіпокампі та обмежує спраутинг в умовах каїнатної моделі СЕ. Позитивний ефект вітаміну Е частково зумовлений його здатністю послаблювати оксидативний стрес

Neuroprotective and Antiapoptotic Potential of Trigonelline in a Striatal 6-Hydroxydopamine Rat Model of Parkinson’s Disease

Considering neuroprotective and antioxidant effects of trigonelline, our study was undertaken to evaluate its protective effect in a 6-hydroxydopamine-induced model of Parkinson’s disease (PD) in rats. Unilateral intrastriatal 6-OHDA-lesioned rats were pretreated with trigonelline at doses of 50 and 100 mg/kg. Significant rotational behavior, a significant reduction in the number of Nissl-stained neurons on the left side of substantia nigra pars compacta (SNC), increased apoptosis, enhanced levels of malondialdehyde (MDA) and nitrite, and a lower level of glutathione (GSH) were observed in 6-OHDA-lesioned rats. Trigonelline at a dose of 100 mg/kg significantly reduced rotations, prevented reduction of SNC neurons, prevented apoptosis, and restored the MDA level. These results suggest that pre-lesion trigonelline treatment exerts dose-dependent neuroprotective and antiapoptotic effects under conditions of 6-OHDA toxicity and may be, henceforth, advantageous for the management of early PD.Беручи до уваги нейропротекторний та антиоксидантний вплив тригонелліну, ми дослідили його захисну дію в моделі хвороби Паркінсона у щурів, індукованій стереотаксичним уведенням 6-гідроксидофаміну (6-OHDA). Щурам, котрим робили унілатеральні ін’єкції 6-OHDA в стріатум, попередньо щоденно тричі вводили тригонеллін у дозах 50 і 100 мг/кг. В умовах використаної 6-OHDA-моделі істотно посилювалась обертальна моторна поведінка, викликана ін’єкцією апоморфіну, значно знижувалася кількість забарвлених, за Ніслем, нейронів у лівій половині компактної частини чорної субстанції, посилювався процес апоптозу нейронів, зростали рівні малональдегіду та нітриту та знижувався рівень відновленого глутатіону. Тригонеллін у щоденних дозах 100 мг/кг вірогідно знижував кількість обертальних рухів, протидіяв зменшенню числа нейронів у чорній субстанції та розвитку апоптозу, а також нормалізував рівень малональдегіду. Отримані результати свідчать про те, що уведення тригонелліну перед ін’єкціями 6-OHDA забезпечує дозозалежні нейропротекторний та антиапоптотичні ефекти в умовах токсичної дії 6-OHDA. Цей агент та його аналоги можуть бути тестовані як допоміжні засоби при лікуванні хвороби Паркінсона на ранніх стадіях

The effect of Zingiber officinalis L. on learning and memory in rats

A B S T R A C T Background and Objective: According to the importance of learning and memory in the human life and also unavoidable neural degeneration due to aging, finding new compounds (drugs) against this process is valuable. However, there are many recommendations for herbal medicine and constituents which encouraged us to examine a candidate plant Zingiber officinalis for the mentioned purpose. Materials and Methods: Male rats (250-300 g) were divided into control and treatment groups. Treatment groups consist of three subgroups including oral (plant was prescribed to animals mixed in food at a ratio of 6.25%) for 2 weeks, and two groups that received the plant extract at doses of 50 and 100 mg/kg (intraperitoneal, IP). In order to investigate the spatial recognition (alternation) behavior and acquisition-recalling (step through latency, STL), the animals were subjected to Y maze and shuttle box tests, respectively. Results: In our study, the difference of the initial latency (IL) in oral treatment groups (8.24±1.21 s) and injection (50 and 100 mg/kg) groups versus control group (14.28±1.45 s) were non-significant. However, step through latency (STL) time difference for oral (18.12±0.8 s) group versus control one (13.28±1.33 s) was significant (p<0.05). Alternation behavior percentage in injection group (100 mg/kg) and oral one was significant versus control animals (p<0.05). Conclusion: Oral and intraperitoneal administration of the Zingiber officinalis could have a significant improving effect on acquisition, retention and recall

Original Article Antioxidant and Antiepileptic Activity of 1-[1-(3-Methoxyphenyl) (Tetralyl)] Piperidine as a New Derivative of Phencyclidine on Pentylentetrazole-Induced Kindling Mice

ABSTRAC

Protective effect of chlorogenic acid in an experimental model of Parkinson’s disease induced by 6-hydroxydopamine in rats

Introdution: Parkinson's disease is the second most common neurodegenerative disease. Considering the antioxidant and neuroprotective properties of chlorogenic acid, the purpose of this study was to evaluate the neuroprotective effect of this substance in an experimental model of Parkinson's disease. Methods: In this experimental study, Wisar male rats (n = 32) were divided into 4 groups: sham, chlorogenic acid-treated sham, lesion and chlorogenic-acid-treated lesion. The experimental model of Parkinson's disease was made by injecting 12.5 microgram of 6-hydroxydopamine dissolved in a saline-ascorbate solution into the left side of neostriatum. The chlorogenic acid-treated sham and the chlorogenic-acid-treated lesion groups received 10 mg/kg of the drug intraperitoneally daily during a week before stereotaxic surgery and the last injection was given one hour before stereotaxic surgery. In the second week after surgery, the rotational behavior induced by apomorphine injection within one hour and the number of dopaminergic neurons in the substantia nigra compacta was examined and counted. For statistical analysis, one-way ANOVA and Tukey post-host tests were used in Sigmaplot 12. Results: Chlorogenic acid-pretreated lesion group showed significantly lower rotations versus lesion group (p<0.01). In addition, chlorogenic acid-treated lesion group had a higher number of dopaminergic neurons relative to lesion group (p<0.05). Conclusion: Pretreatment with chlorogenic acid reduces motor asymmetry in an experimental model of Parkinson's disease and has also protective effect on nigral dopaminergic neurons

Hypericum Perforatum Hydroalcoholic Extract Mitigates Motor Dysfunction and is Neuroprotective in Intrastriatal 6-Hydroxydopamine Rat Model of Parkinson�s Disease

Parkinson�s disease is the second most common neurodegenerative disorder with selective and progressive decline of nigral dopaminergic neurons. Hypericum perforatum L. (H. perforatum, St. John�s wort) has been traditionally used for management of different disorders, especially mild-to-moderate depression. This study was conducted to evaluate the effect of H. perforatum extract against unilateral striatal 6-hydroxydopamine (6-OHDA) toxicity and to unmask some involved mechanisms. Intrastriatal 6-OHDA-lesioned rats were treated with H. perforatum hydroalcoholic extract at a dose of 200 mg/kg/day started 1 week pre-surgery for 1 week post-surgery. The extract attenuated apomorphine-induced rotational behavior, decreased the latency to initiate and the total time on the narrow beam task, lowered striatal level of malondialdehyde and enhanced striatal catalase activity and reduced glutathione content, normalized striatal expression of glial fibrillary acidic protein, tumor necrosis factor α with no significant effect on mitogen-activated protein kinase, lowered nigral DNA fragmentation, and prevented damage of nigral dopaminergic neurons with a higher striatal tyrosine hydroxylase immunoreactivity. These findings reveal the beneficial effect of H. perforatum via attenuation of DNA fragmentation, astrogliosis, inflammation, and oxidative stress. © 2015, Springer Science+Business Media New York

Involvement of Bax and Bcl2 in Neuroprotective Effect of Curcumin in Kainic Acid-Induced Model of Temporal Lobe Epilepsy in Male Rat

Background & objectives: Temporal lobe epilepsy is associated with neuronal apoptosis. Curcumin has antioxidant and anticonvulsant activities, therefore this study was conducted to assess involvement of Bax and Bcl2 in protective effect of curcumin in epileptic rats. Methods: 28 rats were divided into sham, curcumin-pretreated sham, epileptic (kainate), and curcumin-pretreated epileptic groups. Experimental model of epilepsy was induced by intrahippocampal administration of kainic acid. Rats received curcumin at a dose of 100 mg/kg. Finally, Nissl staining and Bax and Bcl2 immunohistochemistry were conducted on hippocampal sections and data were analyzed using one-way ANOVA and unpaired t-test. The p-value less than 0.05was considered statistically significant. Results: Induction of epilepsy was followed by a significant seizure and curcumin pretreatment significantly reduced seizure intensity (p<0.01). In addition, there were no significant differences between the groups in Nissl staining of CA3 area neurons. In addition, Bax positive neurons were observed in CA3 area in kainate group and significantly decreased in curcumin pretreated rats (p<0.05). Meanwhile, Bcl2 positive neurons were also moderately observed in kainate group and curcumin pretreatment significantly increased it (p<0.05). Conclusion: Curcumin pretreatment exhibits anticonvulsant activity in epileptic rats. It also decreases the expression of pro-apoptotic protein Bax and significantly enhances the expression of anti-apoptotic protein Bcl2 and hence could reduce neuronal apoptosis

Effect of acetyl L carnitine on oxidative stress markers in hippocampus of epileptic rat

Background and Aim: Epilepsy is a rather common neurological disorder. Oxidative stress plays an important role in the pathogenesis of epilepsy. The present study was undertaken to evaluate the effect of acetyl L carnitine (ALC) on oxidative stress markers in hippocampus of epileptic rat. Materials and Methods: In this experimental study, male rats were divided into sham, epileptic, valproic acid-treated epileptic ones at a dose of 200mg/kg, and 3 ALC-treated epileptic groups at doses of 50 and 100mg/kg for 3 days pre-surgery. Seizure activity was determined in 4 h periods and for measurement of oxidative stress markers, level of malondialdehyde (MDA), nitrite, and activity of superoxide dismutase (SOD) were determined in hippocampal homogenate. The obtained datawas fed into SPSS software (V:16) and for statistical analysis, one-way ANOVA and x2 tests were used. Results: ALC treatment at doses of 50 and 100 mg/kg attenuated seizure intensity (P<0.05 and P<0.01, respectively), level of MDA significantly reduced (P<0.05) following ALC at a dose of 50 mg/kg, but nitrite level and SOD activity did not show significant changes. Conclusion: ALC pretreatment has antiepileptic activity and at a dose of 50 mg/kg can reduce MDA level as an index of lipid peroxidation but it has no appropriate effect on nitrite level and SOD activity

Effects of alcoholic extract of Zingiber officinalis rhizome on acute and chronic inflammation and pain in rats

Introduction: Patients with chronic, painful diseases often seek alternative therapy. The rhizome of Zingiber (Z) officinalis is a common constituent of diets around the world and its extracts have been reported to exhibit several pharmacological activities. We investigated the effects of alcoholic Zingiber oficinalis rhizome extract on two different models of acute and chronic inflammation and pain. Material and Methods: Formalin, xylen and acetic acid were used to induce acute inflammation in paw, ear and peritoneum, respectively. The amount of Evans' blue dye leakage into these tissues was used as an index of acute inflammation . For chronic inflammation, a piece of sterile cotton (30 mg) was impalnated into the groin region for a period of seven days. Following, t he weight of the cotton piece before implantation is subtracted from the weight of the dried piece and used as an index of chronic inflammation. Finally, acute and chronic pain assessment was carried out via the formalin test protocol . Results: In acute inflammation model, the formalin-induced inflammation in paw and peritoneum was significantly (P <0.05) reduced by the extract of Z. oficinalis rhizome at doses of 200 and 400 mg/kg. Also, the extract at the dose of 400mg/kg significantly (P<0.05) reduced the paw diameter. In chronic inflammation model, the extract at the dose of 200 mg/kg significantly (P< 0.01) dimished inflammation. Finally, both acute and chronic pain significantly (P< 0.05) suppressed by the extract at the dose of 200 mg/kg. Conclusion: Findings of this study indicate that alcoholic extract of Z. oficinalis has anti-inflammatory and antinociceptive effects. Thus, using the extract of Z. oficinalis could be a potential alternative therapy in ameliorating inflammation and pain in patients suffering from chronic diseases