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

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

Protective Effect of Oral Hesperetin Against Unilateral Striatal 6-Hydroxydopamine Damage in the Rat

Parkinson�s disease (PD) is a neurodegenerative disorder due to loss of dopaminergic neurons in the substantia nigra pars compacta (SNC). PD finally leads to incapacitating symptoms including motor and cognitive deficits. This study was undertaken to assess protective effect of the flavanone hesperetin against striatal 6-hydroxydopamine lesion and to explore in more detail some underlying mechanisms including apoptosis, inflammation and oxidative stress. In this research study, intrastriatal 6-hydroxydopamine (6-OHDA)-lesioned rats received hesperetin (50 mg/kg/day) for 1 week. Hesperetin reduced apomorphine-induced rotational asymmetry and decreased the latency to initiate and the total time on the narrow beam task. It also attenuated striatal malondialdehyde and enhanced striatal catalase activity and GSH content, lowered striatal level of glial fibrillary acidic protein as an index of astrogliosis and increased Bcl2 with no significant change of the nuclear factor NF-kB as a marker of inflammation. Hesperetin treatment was also capable to mitigate nigral DNA fragmentation as an index of apoptosis and to prevent loss of SNC dopaminergic neurons. This study indicated the protective effect of hesperetin in an early model of PD via attenuation of apoptosis, astrogliosis marker and oxidative stress and it may be helpful as an adjuvant therapy for management of PD at its early stages. © 2015, Springer Science+Business Media New York

Effect of methadone and valproate combination on morphine withdrawal-induced anxiety and depression in male mice

Background and Objective: Anxiety and depression are experienced following addicted patients durg withdrawal. This study was done to determine the effect of methadone and valproate combination on morphine withdrawal-induced anxiety and depression in male mice. Methods: In this experimental study, ninety-eight male mice were allocated into acute and chronic categories. Animals in acute chronic categories allocated into seven groups including: saline, morphine, methadone (10 mg/kg/bw), valproate (150 mg/kg/bw), three groups of valproate+methadone, in of ratio 1:1, 2:1 and 1:2. Animals were received escalating dose of morphine for 8 consecutive days except saline group. In chronic group, drugs were injected for 30 minutes before morphine administration, while in acute group the drugs were used only at day 8. Anxiety and depression due to naloxone injection (5 mg/kg/bw) was investigated by elevated plus-maze, tail-suspension and open field tests. Results: In the chronic group, valproate + methadone (2:1) combination therapy showed a significant increase in the percentage of open arm entries (53.86±1.9) and percentage of time spent in the open arm (58.58±4.15) compared to the morphine group, with a percentage of entering (28.12±2.03) and percentage of time (17.88±1.77) (P<0.05). In open field test, the ratio of the number to the duration of time spent in the central square, in the combination therapy groups of methadone+valproate (27±2), valproate+methadone (1:2) and valproate+methadone (2:1) were significantly increased in compare to the morphine group (P<0.05). In tail-suspension test, duration of immobility as an indicator of depression, in the treatment group of valproate+methadone (2:1) was significantly reduced (P<0.05). Conclusion: Valproate and methadone combination therapy particularly in ratio of 2:1 can reduce morphine withdrawal-induced anxiety and depression in animal model

Carnosine ameliorates cognitive deficits in streptozotocin-induced diabetic rats: Possible involved mechanisms

Diabetic patients are at increased risk to develop cognitive deficit and senile dementia. This study was planned to assess the benefits of chronic carnosine administration on prevention of learning and memory deterioration in streptozotocin (STZ)-diabetic rats and to explore some of the involved mechanisms. Rats were divided into 5 groups: i.e., control, carnosine100-treated control, diabetic, and carnosine-treated diabetics (50 and 100 mg/kg). Carnosine was injected i.p. at doses of 50 or 100 mg/kg for 7 weeks, started 1 week after induction of diabetes using streptozotocin. Treatment of diabetic rats with carnosine at a dose of 100 mg/kg at the end of the study lowered serum glucose, improved spatial recognition memory in Y maze, improved retention and recall in elevated plus maze, and prevented reduction of step-through latency in passive avoidance task. Furthermore, carnosine at a dose of 100 mg/kg reduced hippocampal acetylcholinesterase (AChE) activity, lowered lipid peroxidation, and improved superoxide dismutase (SOD) activity and non-enzymatic antioxidant defense element glutathione (GSH), but not activity of catalase. Meanwhile, hippocampal level of nuclear factor-kappaB (NF-κB), tumor necrosis factor α (TNF-α), and glial fibrillary acidic protein (GFAP) decreased and level of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) increased upon treatment of diabetic group with carnosine at a dose of 100 mg/kg. Taken together, chronic carnosine treatment could ameliorate learning and memory disturbances in STZ-diabetic rats through intonation of NF-κB/Nrf2/HO-1 signaling cascade, attenuation of astrogliosis, possible improvement of cholinergic function, and amelioration of oxidative stress and neuroinflammation. © 2016 Elsevier Inc

Oral pelargonidin exerts dose-dependent neuroprotection in 6-hydroxydopamine rat model of hemi-parkinsonism

Parkinson's disease (PD) is a neuropathological and debilitating disorder involving the degeneration of mesencephalic dopaminergic neurons. Neuroprotective effect of pelargonidin (Pel) has already been reported, therefore, this study examined whether Pel administration would attenuate behavioural and structural abnormalities and markers of oxidative stress in an experimental model of PD in rat. For this purpose, unilateral intrastriatal 6-hydroxydopamine (6-OHDA, 12.5μg/5μl of saline-ascorbate)-lesioned rats were pre-treated p.o. with Pel (10 and/or 20. mg/kg). Pel administration dose-dependently attenuated the rotational behavior in lesioned rats and protected the neurons of SNC against 6-OHDA toxicity. In addition, pre-treatment with Pel (20. mg/kg) significantly decreased the 6-OHDA-induced thiobarbituric acid reactive substances (TBARS) formation, indicative of a neuroprotection against lipid peroxidation. Furthermore, the increase of nitrite levels induced by 6-OHDA, indicate the nitric oxide formation and free radicals production and the decrease of antioxidant defense enzyme superoxide dismutase (SOD) was non-significantly prevented by Pel (20. mg/kg). In summary, Pel administration has a dose-dependent neuroprotective effect against 6-OHDA toxicity, partly through attenuating oxidative stress. Our findings suggest that pelargonidin could provide benefits, along with other therapies, in neurodegenerative disorders including PD. © 2010 Elsevier Inc

Diosgenin Attenuates Cognitive Impairment in Streptozotocin-Induced Diabetic Rats: Underlying Mechanisms

Objective: Prolonged diabetes mellitus causes impairments of cognition and attentional dysfunctions. Diosgenin belongs to a group of steroidal saponins with reported anti-diabetic and numerous protective properties. This research aimed to assess the effect of diosgenin on beneficially ameliorating learning and memory decline in a rat model of type 1 diabetes caused by streptozotocin (STZ) and to explore its modes of action including involvement in oxidative stress and inflammation.Methods:Rats were assigned to one of four experimental groups, comprising control, control under treatment with diosgenin, diabetic, and diabetic under treatment with diosgenin. Diosgenin was given daily p.o. (40 mg/kg) for 5 weeks. Results: The administration of diosgenin to the diabetic group reduced the deficits of functional performance in behavioral tests, consisting of Y-maze, passive avoidance, radial arm maze, and novel object discrimination tasks (recognitive). Furthermore, diosgenin treatment attenuated hippocampal acetylcholinesterase activity and malon-dialdehyde, along with improvement of antioxidants such as superoxide dismutase and glutathione. Meanwhile, the hippocampal levels of inflammatory indicators, namely interleukin 6, nuclear factor-κB, toll-like receptor 4, tumor necrosis factor α, and astrocyte-specific biomarker glial fibrillary acidic protein, were lower and, on the other hand, tissue levels of nuclear factor (erythroid-derived 2)-related factor 2 were elevated upon diosgenin administration. Besides, the mushroom-like spines of the pyramidal neurons of the hippocampal CA1 area decreased in the diabetic group, and this was alleviated following diosgenin medication. Conclusions: Taken together, diosgenin is capable of ameliorating cognitive deficits in STZ-diabetic animals, partly due to its amelioration of oxidative stress, inflammation, astrogliosis, and possibly improvement of cholinergic function in addition to its neuroprotective potential. © 2020 S. Karger AG, Basel. Copyright: All rights reserved

Berberine ameliorates lipopolysaccharide-induced learning and memory deficit in the rat: insights into underlying molecular mechanisms

Systemic lipopolysaccharide (LPS) triggers neuroinflammation with consequent development of behavioral and cognitive deficits. Neuroinflammation plays a crucial role in the pathogenesis of neurodegenerative disorders including Alzheimer�s disease (AD). Berberine is an isoquinoline alkaloid in Berberis genus with antioxidant and anti-inflammatory property and protective effects in neurodegenerative disorders. In this research, beneficial effect of this alkaloid against LPS-induced cognitive decline was assessed in the adult male rats. LPS was intraperitoneally administered at a dose of 1 mg/kg to induce neuroinflammation and berberine was given via gavage at doses of 10 or 50 mg/kg, one h after LPS, for 7 days. Treatment of LPS group with berberine at a dose of 50 mg/kg (but not at a dose of 10 mg/kg) improved spatial recognition memory in Y maze, performance in novel object recognition task (NORT), and prevented learning and memory dysfunction in passive avoidance tasks. Furthermore, berberine lowered hippocampal activity of acetylcholinesterase (AChE), malondialdehyde (MDA), protein carbonyl, activity of caspase 3, and DNA fragmentation and improved antioxidant capacity through enhancing glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase, and glutathione (GSH). Besides, berberine attenuated inflammation-related indices, as was evident by lower levels of nuclear factor-kappa B (NF-κB), toll-like receptor 4 (TLR4), tumor necrosis factor α (TNFα), and interleukin 6 (IL-6). Berberine also appropriately restored hippocampal 3-nitrotyrosine (3-NT), cyclooxygenase 2 (Cox 2), glial fibrillary acidic protein (GFAP), sirtuin 1, and mitogen-activated protein kinase (p38 MAPK) with no significant alteration of brain-derived neurotrophic factor (BDNF). In summary, berberine could partially ameliorate LPS-induced cognitive deficits via partial suppression of apoptotic cascade, neuroinflammation, oxido-nitrosative stress, AChE, MAPK, and restoration of sirtuin 1. © 2018, Springer Science+Business Media, LLC, part of Springer Nature