Cerebrolysin potentiates the antidepressant effect of lithium in a rat model of depression.

RATIONALE: Depression is the most prevalent psychiatric disorder worldwide. Although numerous antidepressant treatments are available, there is a serious clinical concern due to their severe side effects and the fact that some depressed patients are resistant to them. Lithium is the drug of choice for bipolar depression and has been used as adjunct therapy with other groups of antidepressants. OBJECTIVES: The present study aims to investigate the effect of lithium augmentation with cerebrolysin on the neurochemical, behavioral and histopathological alterations induced in the reserpine model of depression. METHODS: The animals were divided into control and reserpine-induced model of depression. The model animals were further divided into rat model of depression, rat model treated with lithium, rat model treated with cerebrolysin and rat model treated with a combination of lithium and cerebrolysin. RESULTS: Treatment with lithium, cerebrolysin, or their combination alleviated most of the changes in behavior, oxidative stress parameters, acetylcholinesterase and monoamines in the cortex and hippocampus of the reserpine-induced model of depression. It also improved the alterations in brain-derived neurotrophic factor (BDNF) and histopathology induced by reserpine. CONCLUSIONS: The augmentation of lithium with cerebrolysin showed a clear beneficial effect in the present model of depression suggesting the use of cerebrolysin as an adjuvant in antidepressant treatment.

Evaluation of the therapeutic potential of cerebrolysin and/or lithium in the male Wistar rat model of Parkinson's disease induced by reserpine.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease worldwide and represents a challenge for clinicians. The present study aims to investigate the effects of cerebrolysin and/or lithium on the behavioral, neurochemical and histopathological alterations induced by reserpine as a model of PD. The rats were divided into control and reserpine-induced PD model groups. The model animals were further divided into four subgroups: rat PD model, rat PD model treated with cerebrolysin, rat PD model treated with lithium and rat PD model treated with a combination of cerebrolysin and lithium. Treatment with cerebrolysin and/or lithium ameliorated most of the alterations in oxidative stress parameters, acetylcholinesterase and monoamines in the striatum and midbrain of reserpine-induced PD model. It also ameliorated the changes in nuclear factor-kappa and improved the histopathological picture induced by reserpine. It could be suggested that cerebrolysin and/or lithium showed promising therapeutic potential against the variations induced in the reserpine model of PD. However, the ameliorating effects of lithium on the neurochemical, histopathological and behavioral alterations induced by reserpine were more prominent than those of cerebrolysin alone or combined with lithium. It can be concluded that the antioxidant and anti-inflammatory effects of both drugs played a significant role in their therapeutic potency.

Effect of curcumin nanoparticles on streptozotocin-induced male Wistar rat model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that afflicts millions of people all over the world. Intracerebroventricular (ICV) injection of a sub-diabetogenic dose of streptozotocin (STZ) was established as an experimental animal model of AD. The present study was conducted to evaluate the efficacy of curcumin nanoparticles (CNs) against the behavioral, neurochemical and histopathological alterations induced by ICV-STZ. The animals were divided into: control animals, the animal model of AD that received a single bilateral ICV microinjection of STZ, and the animals protected by a daily oral administration of CNs for 6 days before the ICV-STZ injection. The animals of all groups were subjected to surgical operation on the 7th day of administration. Then the administration of distilled water or CNs was continued for 8 days. The ICV-STZ microinjection produced cognitive impairment as evident from the behavioral Morris water maze (MWM) test and induced oxidative stress in the cortex and hippocampus as indicated by the significant increases in lipid peroxidation and nitric oxide (NO) levels and the significant decrease in reduced glutathione (GSH) levels. It also produced a significant increase in acetylcholinesterase (AChE) and tumor necrosis-alpha (TNF-ɑ) and a significant decrease in Na+,K + -ATPase. In addition, a significant increase in amino acid neurotransmitters occurred in the hippocampus, whereas a significant decrease was obtained in the cortex of STZ-induced AD rats. CNs ameliorated the behavioral, immunohistochemical and most of the neurochemical alterations induced by STZ in the hippocampus and cortex. It may be concluded that CNs might be considered as a promising therapeutic agent for the treatment of AD.

A Neurochemical and Electrophysiological Study on the Combined Effects of Caffeine and Nicotine in the Cortex of Rats.

INTRODUCTION: Caffeine and nicotine are the most widely consumed psychostimulants worldwide. Although the effects of each drug alone on the central nervous system have been studied extensively, the literature on the neurochemical and electrophysiological effects of their combined treatments is scarce. The present study investigated the cortical electrophysiological and neurochemical alterations induced by acute administration of caffeine and nicotine in rats. METHODS: The rats received caffeine and nicotine at a 1-hour interval between the two treatments. RESULTS: Caffeine and nicotine administration resulted in a significant decrease in the concentrations of cortical amino acid neurotransmitters, namely glutamate, aspartate, glycine, and taurine, while γ-aminobutyric acid (GABA) significantly increased. Increased cortical lipid peroxidation and reduced glutathione and nitric oxide levels and acetylcholinesterase and Na+/K+-ATPase activities were also observed. The Electroencephalogram (EEG) showed an increase in delta frequency power band, whereas theta, beta-1, and beta-2 decreased after caffeine and nicotine treatment. CONCLUSION: These findings suggest that caffeine and nicotine adversely exacerbate their stimulant effects manifested by the EEG changes mediated by increasing cholinergic transmission and disturbing the balance between the excitatory and inhibitory amino acids leading to oxidative stress.

Neurotoxicity of green- synthesized magnetic iron oxide nanoparticles in different brain areas of wistar rats.

AIMS: The aim of the present study was to evaluate the toxicity of magnetic iron oxide nanoparticles (MIONs) which were synthesized using carob leaf extract on various brain areas of Wistar rats. MAIN METHODS: Carob leaf synthesized-MIONs were characterized using different techniques: Dynamic Light Scattering (DLS), Transmission Electron Microscope (TEM), UV-vis spectrophotometer, Fourier Transform infrared (FTIR), X-Ray Diffraction (XRD) and Atomic Force Microscope (AFM). The toxicity of MIONs in vivo was evaluated by: monitoring rat's body weight, measuring iron content in different brain areas, evaluating some oxidative stress parameters, estimating acetylcholinesterase (AChE) in addition to histopathological investigations. KEY FINDINGS: The present study demonstrated no body weight changes of MIONs- treated rats. According to the conditions of the present study, the hippocampus and striatum were the most affected areas and demonstrated neuronal degeneration due to MIONs exposure. MIONs treatment of Wistar rats, also affected the iron homeostasis in both striatum and midbrain by decreasing iron content in these areas. The least affected areas were thalamus and cerebellum. The histopathological examination of brain areas demonstrated moderate neuronal degeneration in hippocampus and striatum, mild neuronal degeneration in cortex and slight degeneration in hypothalamus and pons-medulla areas were detected. SIGNIFICANCE: The results suggested that MIONs have a toxic impact on different brain areas and the effect varies according to the brain area.

Cerebellar neurochemical and histopathological changes in rat model of Parkinson's disease induced by intrastriatal injection of rotenone.

The aim of the present work was to investigate the neurochemical changes induced in the cerebellum of rat model of Parkinson's disease (PD). Rats were divided into two groups; control and rat model of PD induced by the intrastriatal injection of rotenone. As compared to control, a significant increase in the excitatory amino acid neurotransmitters; glutamate and aspartate together with a significant decrease in the inhibitory amino acids, GABA, glycine and taurine were observed in the cerebellum of rat model of PD. This was associated with a significant increase in lipid peroxidation, nitric oxide and tumor necrosis factor-α and a significant decrease in reduced glutathione. A significant decrease in acetylcholinesterase and a significant increase in Na+,K+-ATPase were recorded in the cerebellum of rat model of PD. In addition the cerebellar sections from rat model of PD showed marked necrosis of Purkinje cells, irregular damaged cells, cytoplasmic shrinkage, necrosis and perineuronal vacuolation. The present results indicate that the disturbance in the balance between the excitatory and inhibitory amino acids may have a role in the pathogenesis of PD. According to the present neurochemical and histopathological changes, the cerebellum should be taken into consideration during the treatment of PD.

A promising therapeutic potential of cerebrolysin in 6-OHDA rat model of Parkinson's disease.

AIMS: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease affecting the population. The present study investigates the potential therapeutic effect of cerebrolysin (CBL), as a neurotrophic factor mimic, on the behavioral and biochemical alterations induced in 6-hydroxydopamine (6-OHDA) - lesioned rats as a model of PD. MAIN METHODS: The animals were divided into 3 experimental groups; control group, Parkinsonian model group through bilateral microinjection of 6-OHDA into substantia nigra (SN) and CBL-treated group which received a daily intraperitoneal administration of CBL (2.5ml/kg) initiated 24h after induction of Parkinsonism for 21days. KEY FINDINGS: Treatment of Parkinsonian animals with CBL succeeded in restoring the midbrain and striatum dopamine levels. In addition, it normalized the increased MDA and NO levels recorded in the Parkinsonian animals and replenished the decreased level of midbrain GSH. In addition to the recorded recovery of the biochemical parameters, there was a parallel improvement in the animal's behavioral aspects. SIGNIFICANCE: The findings of the present study provide evidence for the promising therapeutic effect of CBL in the present 6-OHDA rat model of PD through counteracting oxidative stress, replenishing dopamine content and enhancing behavioral outcomes.

Neurochemical impact of bisphenol A in the hippocampus and cortex of adult male albino rats.

Bisphenol A (BPA), an endocrine-disrupting chemical, is widely used in the manufacture of polycarbonated plastics and epoxy resins and line metal beverage cans. Growing evidence suggests that BPA acts directly on neuronal functions as it is lipophilic and could accumulate in the brain. The present study aims to investigate the effect of two doses of BPA (10 mg/kg for 6 and 10 weeks and 25 mg/kg for 6 weeks) on excitatory (glutamate and aspartate) and inhibitory (γ-aminobutyric acid, glycine, and taurine) amino acid neurotransmitter levels in the cortex and hippocampus. This study extends to investigate the effect of BPA on acetylcholinesterase (AchE) activity and some oxidative stress parameters in the two regions. In the cortex, a significant increase in the excitatory and a significant decrease in the inhibitory amino acids occurred after BPA (10 mg/kg for 10 weeks and 25 mg/kg for 6 weeks). This was accompanied by a significant increase in lipid peroxidation, nitric oxide, and reduced glutathione after 6 weeks of BPA (25 mg/kg). In the hippocampus, a significant increase in the excitatory and inhibitory amino acid neurotransmitters occurred after 6 weeks of BPA. Hippocampal lipid peroxidation increased significantly after BPA exposure and hippocampal reduced glutathione increased significantly after 6 weeks of BPA exposure (10 mg/kg). BPA induced a significant increase in cortical and hippocampal AchE activity. The present neurochemical changes in the cortex and hippocampus suggest that BPA induced a state of excitotoxicity and oxidative stress. This may raise concerns about the exposure of humans to BPA due to its wide applications in industry.

Nigella sativa amliorates inflammation and demyelination in the experimental autoimmune encephalomyelitis-induced Wistar rats.

Multiple sclerosis (MS) is the major, immune-mediated, demyelinating neurodegenerative disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model of MS. The aim of the present study was to investigate the protective and ameliorative effects of N. sativa seeds (2.8 g/kg body weight) in EAE-induced Wistar rats. EAE-induced rats were divided into: 1- EAE-induced rats ("EAE" group). 2- "N. sativa + EAE" group received daily oral administration of N. sativa 2 weeks prior EAE induction until the end of the experiment. 3- "EAE + N. sativa" group received daily oral administration of N. sativa after the appearance of first clinical signs until the end of the experiment. All animals were decapitated at the 28th day post EAE-induction. EAE was investigated using histopathological, immunohistochemical and ultrastructural examinations in addition to determination of some oxidative stress parameters in the cerebellum and medulla. N. sativa suppressed inflammation observed in EAE-induced rats. In addition, N. sativa enhanced remyelination in the cerebellum. Moreover, N. sativa reduced the expression of transforming growth factor beta 1 (TGF ß1). N. sativa seeds could provide a promising agent effective in both the protection and treatment of EAE.

Evaluation of the antiepileptic effect of curcumin and Nigella sativa oil in the pilocarpine model of epilepsy in comparison with valproate.

The present study aimed to investigate the effect of curcumin and Nigella sativa oil (NSO) on amino acid neurotransmitter alterations and the histological changes induced by pilocarpine in the hippocampus and cortex of rats. Epilepsy was induced by i.p. injection of pilocarpine, and the animals were left for 22 days to establish spontaneous recurrent seizures. They were then treated with curcumin, NSO or valproate for 21 days. Pilocarpine induced a significant increase in hippocampal aspartate and a significant decrease in glycine and taurine levels. In the cortex, a significant increase in aspartate, glutamate, GABA, glycine, and taurine levels was obtained after pilocarpine injection. Treatment of pilocarpinized rats with curcumin and valproate ameliorated most of the changes in amino acid concentrations and reduced the histopathological abnormalities induced by pilocarpine. N. sativa oil failed to improve the pilocarpine-induced abnormalities. This may explain the antiepileptic effect of curcumin and suggest its use as an anticonvulsant.

Neurochemical and electrophysiological changes induced by paradoxical sleep deprivation in rats.

The present study aims to investigate the effects of paradoxical sleep deprivation (PSD) on the waking EEG and amino acid neurotransmitters in the hippocampus and cortex of rats. Animals were deprived of paradoxical sleep for 72h by using the multiple platform method. The EEG power spectral analysis was carried out to assess the brain's electrophysiological changes due to sleep deprivation. The concentrations of amino acid neurotransmitters were assessed in the hippocampus and cortex using HPLC. Control data showed slight differences from normal animals in the delta, theta and alpha waves while an increase in the beta wave was obtained. After 24h of PSD, delta relative power increased and the rest of EEG wave's power decreased with respect to control. After 48h and 72h the spectral power analysis showed non-significant changes to control. The amino acid neurotransmitter analysis revealed a significant increase in cortical glutamate, glycine and taurine levels while in the hippocampus, glutamate, aspartate, glutamine and glycine levels increased significantly. Both the waking EEG and neurotransmitter analyses suggest that PSD induced neurochemical and electrophysiological changes that may affect brain proper functionality.

The neuroprotective effect of curcumin and Nigella sativa oil against oxidative stress in the pilocarpine model of epilepsy: a comparison with valproate.

Oxidative stress has been implicated to play a role in epileptogenesis and pilocarpine-induced seizures. The present study aims to evaluate the antioxidant effects of curcumin, Nigella sativa oil (NSO) and valproate on the levels of malondialdehyde, nitric oxide, reduced glutathione and the activities of catalase, Na⁺, K⁺-ATPase and acetylcholinesterase in the hippocampus of pilocarpine-treated rats. The animal model of epilepsy was induced by pilocarpine and left for 22 days to establish the chronic phase of epilepsy. These animals were then treated with curcumin, NSO or valproate for 21 days. The data revealed evidence of oxidative stress in the hippocampus of pilocarpinized rats as indicated by the increased nitric oxide levels and the decreased glutathione levels and catalase activity. Moreover, a decrease in Na⁺, K⁺-ATPase activity and an increase in acetylcholinesterase activity occurred in the hippocampus after pilocarpine. Treatment with curcumin, NSO or valproate ameliorated most of the changes induced by pilocarpine and restored Na⁺, K⁺-ATPase activity in the hippocampus to control levels. This study reflects the promising anticonvulsant and potent antioxidant effects of curcumin and NSO in reducing oxidative stress, excitability and the induction of seizures in epileptic animals and improving some of the adverse effects of antiepileptic drugs.