Yasser A. Khadrawy

Effect of oxidative stress induced by paradoxical sleep deprivation on the activities of Na+, K+-ATPase and acetylcholinesterase in the cortex and hippocampus of rat

Several studies revealed the importance of paradoxical sleep as a homeostatic mechanism by which the brain can control oxidative stress. The aim of the present study is to investigate the effect of 72 h of paradoxical sleep deprivation on the oxidative stress markers and its insults on the activities of Na(+), K(+)-ATPase and acetylcholinesterase in the cortex and hippocampus of albino rat. Animals were subjected to paradoxical sleep deprivation for 72 h. At the end of the experiment, the rats were sacrificed, and catalase activity, levels of reduced glutathione, lipid peroxidation, and nitric oxide were assayed together with the activities of Na(+), K(+)-ATPase and acetylcholinesterase in the cortex and hippocampus. The present study revealed a significant increase in lipid peroxidation accompanied by a significant decrease in reduced glutathione in the cortex and hippocampus. Na(+), K(+)-ATPase decreased significantly in both areas. However, acetylcholinesterase showed a significant increase in the investigated brain regions. The present data showed that 72 h of paradoxical sleep deprivation induced oxidative stress in the cortex and hippocampus. It could be suggested that the inhibition of Na(+), K(+)-ATPase and the increased acetylcholinesterase activity may underlie memory impairment, increased brain excitability, and anxiety induced by paradoxical sleep deprivation.

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 brains 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 waves 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.

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.

One-pot three-component synthesis of novel heterocyclic steroids as a central antioxidant and anti-inflammatory agents.

Oxidative stress and inflammation have been implicated in several neurodegenerative and developmental brain disorders. The present work was devoted to the design and synthesis of novel steroid derivatives bearing promising heterocyclic moiety that would act to reduce neuro-inflammation and oxidative stress in brain. The novel heterocyclic steroids were synthesized and their chemical structures were confirmed by studying their analytical and spectral data. The tested compounds were assayed in the model of neuro-inflammation produced in rats by cerebral lipopolysaccharide injection. The intracerebral administration of bacterial endotoxin resulted in cerebral inflammatory state evidenced by increased malondialdehyde (MDA), decreased reduced glutathione (GSH) level, increased nitric oxide as well as increased acetylcholinesterase (AChE) activity in the brain. Compounds 6, 10, 8b and 13a markedly increased reduced glutathione. Malondialadehyde and nitric oxide levels were reduced to normal values after treatment with all tested compounds. AChE activity was normalized by compound 8b and reduced to below normal values by compounds 10 and 14a. These results are exciting in that these agents might be useful candidates in treatment of cerebral inflammation.

Brain and liver oxidative stress after sertraline and haloperidol treatment in mice

Abstract Background: Haloperidol is a classic antipsychotic drug known for its propensity to cause extrapyramidal side effects. Sertraline is an antidepressant drug which has been reported to cause extrapyramidal symptoms. We aimed to see whether treatment with sertraline would worsen the effect of haloperidol on oxidative stress in the brains of mice. Methods: Sertraline (10 or 20 mg/kg), haloperidol (2 mg/kg), haloperidol combined with sertraline or saline was administered daily via the subcutaneous route and mice were euthanized 10 days later when biochemical assays were carried out. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (nitrite) levels, total antioxidant capacity (TAC), acetylcholinesterase (AChE), catalase and paraoxonase 1 (PON1) activities were determined in the brain and liver. Results: Sertraline monotherapy did not alter GSH, MDA, TAC or nitrite in the brain. Haloperidol decreased GSH and TAC and increased MDA and nitrite. The combined treatment with sertraline and haloperidol resulted in increased MDA, but to a lesser extent than haloperidol monotherapy. A significant increase in GSH and TAC and decreased nitrite was observed after the combination treatment was compared with haloperidol monotherapy. Catalase activity decreased with sertraline or haloperidol treatment. PON1 activity decreased with sertraline and haloperidol monotherapy and showed a further decrease with the combination therapy compared with haloperidol monotherapy. AChE activity decreased after haloperidol and increased with the combination treatment compared with haloperidol monotherapy. In the liver, GSH was unaltered after sertraline, haloperidol or their combination. MDA increased with sertraline, haloperidol and their combination. TAC decreased after combination therapy. Nitric oxide increased after sertraline, haloperidol or their combination. PON1 activity decreased with sertraline, haloperidol and with sertraline-haloperidol co-treatment. Conclusions: Sertraline did not worsen brain oxidative stress-induced with haloperidol, however, liver peroxidation increased. Sertraline decreased catalase and PON1 activity which might expose the brain to further oxidative insults.

The effect of gabapentin on oxidative stress in a model of toxic demyelination in rat brain

Abstract Background: Gabapentin, a structural analog of γ-aminobutyric acid (GABA), is used in the treatment of neuropathic pain in multiple sclerosis. Methods: This study investigated the effect of gabapentin on oxidative stress in a model of brain demyelination evoked by intracerebral injection (i.c.i) of ethidium bromide (10 μL of 0.1%). Rats received saline (control) or gabapentin at 100 or 300 mg/kg orally daily for 10 days prior to injection of ethidium bromide. Rats were euthanized 1 day later, and then the levels of reduced glutathione (GSH), glutathione peroxidase (GPx) activity, lipid peroxidation (malondialdehyde; MDA), nitrite, acetyl cholinesterase (AChE) and paraoxonase activities were assessed in the brain cortex in different treatment groups. Results: Ethidium bromide resulted in increased oxidative stress in the cortex 1 day after its injection. Malondialdehyde increased by 30.2%, whereas GSH decreased by 17.6%. GPx activity was inhibited by 78.6%. Brain nitrite increased by 55.4%, AChE activity decreased by 33.4% and paraoxonase activity decreased by 27.5%. In ethidium bromide treated rats, gabapentin administered at 300 mg/kg increased cortical MDA by 66%. GSH was unaltered by gabapentin, but GPx activity decreased by 54.3% by the higher dose of gabapentin. Nitrite decreased by 21.4% and 29.2% after 100 and 300 mg/kg of gabapentin, respectively. AChE activity increased by 28.6% and 69.3% by 100 and 300 mg/kg of gabapentin, respectively. Paraoxonase activity showed 83.3% and 73% decreases by 100 and 300 mg/kg of gabapentin, respectively. Conclusions: These results suggest that gabapentin increases brain lipid peroxidation and decreases brain antioxidant enzymes in this model of chemical demyelination.

Ozone Therapy in Ethidium Bromide-Induced Demyelination in Rats: Possible Protective Effect.

Multiple sclerosis, an autoimmune inflammatory disease of the central nervous system, is characterized by excessive demyelination. The study aimed to investigate the possible protective effect of ozone (O3) therapy in ethidium bromide (EB)-induced demyelination in rats either alone or in combination with corticosteroids in order to decrease the dose of steroid therapy. Rats were divided into Group (1) normal control rats received saline, Group (2) Sham-operated rats received saline, Group (3) Sham-operated rats received vehicle (oxygen), Group (4) EB-treated rats received EB, Group (5) EB-treated rats received O3, Group (6) EB-treated rats received methylprednisolone (MP), and Group (7) EB-treated rats received half the dose of MP concomitant with O3. EB-treated rats showed a significant increase in the number of footfalls in the grid walk test, decreased brain GSH, and paraoxonase-1 enzyme activity, whereas brain MDA, TNF-α, IL-1β, INF-γ, Cox-2 immunoreactivity, and p53 protein levels were increased. A significant decline in brain serotonin, dopamine, norepinephrine, and MBP immunoreactivity was also reported. Significant improvement of the above-mentioned parameters was demonstrated with the administration of either MP or O3, whereas best amelioration was achieved by combining half the dose of MP with ozone.

Neuroprotective and Therapeutic Effect of Caffeine on the Rat Model of Parkinson's Disease Induced by Rotenone

ABSTRACT The present study aimed to investigate the protective and therapeutic effects of caffeine on rotenone-induced rat model of Parkinsons disease (PD). Rats were divided into control, PD model induced by rotenone (1.5 mg/kg intraperitoneally (i.p.) for 45 days), protected group injected with caffeine (30 mg/kg, i.p.) and rotenone for 45 days (during the development of PD model), and treated group injected with caffeine (30 mg/kg, i.p.) for 45 days after induction of PD model. The data revealed a state of oxidative and nitrosative stress in the midbrain and the striatum of animal model of PD as indicated from the increased lipid peroxidation and nitric oxide levels and the decreased reduced glutathione level and activities of glutathione-S-transferase and superoxide dismutase. Rotenone induced a decrease in acetylcholinesterase and Na+/K+-ATPase activities and an increase in tumor necrosis factor-α level in the midbrain and the striatum. Protection and treatment with caffeine ameliorated the oxidative stress and the changes in acetylcholinesterase and Na+/K+-ATPase activities induced by rotenone in the midbrain and the striatum. This was associated with improvement in the histopathological changes induced in the two areas of PD model. Caffeine protection and treatment restored the depletion of midbrain and striatal dopamine induced by rotenone and prevented decline in motor activities (assessed by open field test) and muscular strength (assessed by traction and hanging tests) and improved norepinephrine level in the two areas. The present study showed that caffeine offered a significant neuroprotection and treatment against neurochemical, histopathological, and behavioral changes in a rotenone-induced rat model of PD.

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

AIMS Parkinsons 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 animals 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.

Cerebrolysin protects against rotenone-induced oxidative stress and neurodegeneration

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Journal of Neurorestoratology 2014:2 47–63 Journal of Neurorestoratology Dovepress