Brain Malondialdehyde Levels Research Articles

Lycopene ameliorates propionic acid-induced autism spectrum disorders by inhibiting inflammation and oxidative stress in rats.

This study was conducted to study lycopene efficacy in brain-behavior, pro-inflammatory and apoptotic markers, and antioxidant levels in a rodent model. Rats were administered with propionic acid (PPA) (500mg/kg BW) to induce autism-like disorders, then treated with different lycopene (L) concentrations (5, 10, 20mgkg-1 day-1 ) for 35days. The groups were: (i);control, (ii);PPA, (iii);PPA + L5, (iv);PPA + L10, and (v);PPA + L20. In this study, serum and brain malondialdehyde (MDA) levels decreased with lycopene supplements compared to the PPA group, similarly to the brain levels of inflammatory factors (IL-1α, IL-8, NF-κB, TNF-α; p<.05). Besides, brain levels of anti-apoptotic Bcl-2 decreased, whereas pro-apoptotic Bax, antioxidant Nrf2, and HO-1 levels in brain increased compared with PPA (p<.05). This study showed that lycopene might have therapeutic value to improve the dysfunctions in learning and memory in a dose-dependent way, along with the antioxidant, anti-inflammatory, and antiapoptotic molecular responses in a rat model of ASD-like disorders. PRACTICAL APPLICATIONS: This study suggested that lycopene can reduce propionic acid (PPA)-induced learning and memory impairment and oxidative damage by participating in multiple biological activities such as antioxidant, and anti-inflammatory effects. Lycopene protects serum and brain tissues against PPA induced oxidative damage in rats. These effects may be realized through up-regulation of the brain Nrf2/HO-1 pathway and down-regulation of the IL-1α, IL-8, TNF-α, and NF-κB levels. Lycopene may also contribute to memory and learning function, apoptotic/antiapoptotic modulation, and antioxidant and possible therapeutic efficacy in PPA-induced- Autism spectrum disorder cases.

Effects of intrauterine infection in different periods on the placenta and endometrial blood vessel formation of pregnant mice and the growth and development of fetal rats

Objective: To investigate the effects of intrauterine infection in different periods on the placenta and endometrial blood vessel formation of pregnant rats and the growth and development of fetal rats.Methods: According to the random number table method, 32 pregnant rats were divided into the early infection group, the mid-term infection group, the late infection group and the control group, with 8 rats in each group. On the 3rd, 9th and 15th day of pregnancy, lipopolysaccharide was injected intraperitoneally to construct intrauterine infection models. The pregnant rats in the control group were intraperitoneally injected with the same dose of 0.9% sodium chloride solution. On the 18th day of pregnancy, the inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)], the blood vessel density of placenta and endometrium in the placental tissues of pregnant rats, dead fetus + absorbed fetus, the inflammatory factors IL-6, TNF-α and oxidation reaction indicators [malondialdehyde (MDA) and myeloperoxidase (MPO)] in the fetal rat lung and brain tissues were detected.Results: The changing trend of IL-6 and TNF-α levels in the placental tissues of pregnant rats with intrauterine infection in different periods was: the control group &lt; the late infection group &lt; the mid-term infection group &lt; the early infection group, the differences were statistically significant (p &lt;.05). The changing trend of fetal rat weight, placental weight and placental coefficient in the intrauterine infection groups in different periods was: the control group &gt; the late infection group &gt; the mid-term infection group &gt; the early infection group, the differences were statistically significant (p &lt; .05). The blood vessel density of placenta and endometrium, the mean number of fetuses, brain coefficient and lung coefficient in the late infection group were significantly increased in comparison with the early infection group and the mid-term infection group. The total number and the ratio of dead fetus + absorbed fetus, the levels of IL-6, TNF-α, MDA and MPO in brain and lung tissues were significantly reduced, and the differences were statistically significant (p &lt; .05). The blood vessel density of placenta and endometrium, brain coefficient and lung coefficient of pregnant rats in the mid-term infection group were significantly increased in comparison with the early infection group, and the differences were statistically significant (p &lt; .05). There was no statistically significant difference in the other indicators between the two groups (p &gt; .05).Conclusions: Intrauterine infection in different periods can inhibit placental and endometrial angiogenesis, and affect the survival rate of fetal rats and the growth and development of brain and lung. The reason may be related to the aggravation of fetal inflammatory responses and oxidative stress. The earlier the intrauterine infection occurs, the severer the adverse effects on the fetal rats will be.

Concentration-dependent Effects of Dietary L-Ascorbic Acid Fortification in the Brains of Healthy Mice

Ascorbic acid (AA) is a water-soluble vitamin that is concentrated in the brain in large quantities. There have been reports that it is essential for proper brain functioning. However, there is insufficient information on the possible effects of dietary fortification with AA on the health of the brain. This study examined the effects of dietary fortification of rodent chow with AA on neurobehaviour, antioxidant status, lipid peroxidation, and inflammatory/apoptotic markers in the brain of healthy mice. Mice were randomly assigned into four groups of ten animals each. Groups were normal control [fed rodent chow], and three groups were fed AA-fortified chow at 100, 200, and 300 mg/kg of feed, respectively, for eight weeks. Behavioural tests {Open field, Y-maze, radial-arm maze, and elevated plus maze (EPM)} were carried out on day 57. Twenty-four hours after the last behavioural test, animals were euthanised, and the brains were excised and homogenised for assessment of brain acetylcholinesterase activity, lipid peroxidation, antioxidant status, inflammatory and apoptotic markers. Ascorbic acid fortified diet was associated with concentration-dependent changes in body weight, open-field behaviours, working-memory, and anxiety indices. Also, brain levels of malondialdehyde, caspase-3, and TNF-α decreased, while superoxide dismutase activity, total antioxidant capacity, and IL-10 level increased. Dietary AA fortification with concentrations up to 300 mg/kg of feed was associated with sustained improvement in neurobehavioural and biochemical parameters in the brain of healthy mice, reiterating additional health benefits of AA fortification beyond the prevention of nutritional deficiencies.

Melatonin Improves Reduced Activities of Membrane ATPases and Preserves Ultrastructure of Gray and White Matter in the Rat Brain Ischemia/Reperfusion Model.

Ischemia/reperfusion (I/R) is among the most frequent neurological problems and early intervention to limit the damage is crucial in decreasing mortality and morbidity. Based on reports regarding beneficial effects of melatonin, we investigated its impact on Na+-K+/Mg2+ ATPase and Ca2+/Mg2+ ATPase activities and ultrastructure of gray and white matter in the rat forebrain I/R model. Adult Wistar-albino rats (n = 78), were randomized into control, ischemia (I), ischemia/reperfusion (I/R), low (I/R + melatonin 400 µg/kg), moderate (I/R + melatonin 1200 µg/kg), and high (I/R + melatonin 2400 µg/kg) dose melatonin. Two-vessel occlusion combined with hypotension (15 min) induced ischemia and reperfusion (75 min) achieved by blood reinfusion were performed. Activities of the membrane-bound enzyme, brain malondialdehyde levels, and brain matter ultrastructure were examined in frontoparietal cortices. Melatonin lowered production of malondialdehyde in a dose-dependently. The enzyme activities attenuated under I and I/R, improved with melatonin treatment. I and I/R severely disturbed gray and white matter morphology. Melatonin, in all applied doses, decreased ultrastructural damages in both gray and white matter. Favorable effects of melatonin can be attributed to its antioxidant properties suggesting that it could be a promising neuroprotective agent against I/R injury being effective both for gray and white matter due to favorable biological properties.

Exposure to prolonged unpredictable light impairs spatial memory via induction of oxidative stress and tumor necrosis factor-alpha in rats.

The human body physiology rapidly changes and adapt to several environmental stimuli, including light. Abnormal artificial light exposures have been shown to affect sleep cycle, cognition, and mood. Although studies have reported inconsistent effects of short-term or constant long-term light exposures, human exposures to artificial lights occur at varying, unpredictable times and duration daily. Here, we studied the effects of long-term unpredictable light exposure on learning, memory, oxidative status, and associated cytokines in rats. Artificial lighting was provided using an array of white light-emitting diodes coupled to a microcontroller that switches them on or off at unpredictable times and duration (light intensity=200±20lx). Within the last eight days of 40days exposure, animals were subjected to open field test, Morris water maze, and novel object recognition behavioral paradigms. Brain levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase, reduced glutathione (GSH), glutathione S-transferase (GST), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) were assayed. Exposed rats showed impaired spatial learning and memory (p<0.05), but no changes in object recognition memory or locomotor activity. Oxidative stress analyses also revealed significant changes in the concentrations of MDA, SOD, catalase, and GSH levels (p<0.05), not GST. Similarly, there was an increased TNF-α expression (p<0.05), not VEGF. We conclude that oxidative stress is involved in memory impairment in rats exposed to prolonged unpredictable lights, which again suggests the detrimental effects of extended light exposure on the nervous system.

Effects of radiofrequency electromagnetic radiation emitted from a mobile phone base station on the redox homeostasis in different organs of Swiss albino mice

ABSTRACT This study was designed to investigate the possible effects of exposure to mobile phone base station (MPBS) emits 1800-MHz RF-EMR on some oxidative stress parameters in the brain, heart, kidney and liver of Swiss albino mice under exposures below thermal levels. Mice were randomly assigned to three experimental groups which were exposed to RF-EMR for 6 hr/day, 12 hr/day and 24 hr/day for 45 consecutive days, respectively, and a control group. The glutathione (GSH) levels and activities of glutathione-s-transferase (GST) and superoxide dismutase (SOD) were significantly reduced in mice brain after exposure to RF-EMR for 12 hr and 24 hr per day. Exposure of mice to RF-EMR for 12 hr and 24 hr per day also led to a significant increase in malondialdehyde (an index of lipid peroxidation) levels in mice brain. On the contrary, exposures used in this study did not induce any significant change in various oxidative stress-related parameters in the heart, kidney and liver of mice. Our findings showed no significant variations in the activities of aspartate amino-transferase (AST), alanine amino-transferase (ALT), and on the level of creatinine (CRE) in the exposed mice. This study also revealed a decrease in RBC count with an increase in WBC count in mice subjected to 12 hr/day and 24 hr/day exposures. Exposure to RF-EMR from MPBS may cause adverse effects in mice brain by inducing oxidative stress arising from the generation of reactive oxygen species (ROS) as indicated by enhanced lipid peroxidation, and reduced levels and activities of antioxidants.

The Hepatoprotective mechanisms of 17β-estradiol after traumatic brain injury in male rats: Classical and non-classical estrogen receptors

Protective effects of estrogen (E2) on traumatic brain injury (TBI) have been determined. In this study, the hepatoprotective effects of E2 after TBI through its receptors and oxidative stress regulation have been evaluated. Diffuse TBI induced by the Marmarou method in male rats. G15, PHTPP, MPP, and ICI182–780 as selective antagonists of E2 were injected before TBI. The results indicated that TBI induces a significant increase in liver enzymes [Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Glutamyl transferase (GGT)], and oxidants levels [Malondialdehyde (MDA), Nitric oxide (NO)] and decreases in antioxidant biomarkers [Glutathione peroxidase (GPx) and Superoxide dismutase (SOD)] in the brain and liver, and plasma. We also found that E2 significantly preserved levels of these biomarkers and enzymatic activity. All antagonists inhibited the effects of E2 on increasing SOD and GPx. Also, the effects of E2 on brain MDA levels were inhibited by all antagonists, but in the liver, only ICI + G15 + E2 + TBI group was affected. The impacts of E2 on brain and liver and plasma NO levels were inhibited by all antagonists. The current findings demonstrated that E2 probably improved liver injury after TBI by modulating oxidative stress. Also, both classic (ERβ, ERα) and non-classic [G protein-coupled estrogen receptor (GPER)] receptors are affected in the protective effects of E2.

The effect of sulfasalazine in pentylenetetrazole-induced seizures in rats.

We aimed to reveal the anti-convulsant effects sulfasalazine and its mechanism in pentylenetetrazole (PTZ)-induced seizures in rats. Forty-eight male Wistar albino rats (200-250 g) were randomly divided into two groups: 24 for electroencephalography (EEG) recording (group A) and 24 for behavioral studies (group B). About 70 mg/kg PTZ was used for behavioral studies after sulfasalazine administration and 35 mg/kg PTZ was used for EEG recording after sulfasalazine administration. Electrodes were implanted on the dura mater over the left frontal cortex and the reference electrode was implanted over the cerebellum for EEG recording. Racine’s convulsion scale, first myoclonic jerk onset time, spike percentages, brain malondialdehyde (MDA), superoxide dismutase (SOD), and prostaglandin F2α (PGF2α) levels were evaluated between the groups. First myoclonic jerk onset time was significantly shorter in the saline group than both 250 and 500 mg/kg sulfasalazine groups (P<0.05). Racine's convulsion scores were significantly lower in the 250 and 500 mg/kg sulfasalazine groups than the saline group (P<0.05, P<0.001). The two sulfasalazine groups had lower spike percentages than the saline group (P<0.05). Significantly lower MDA and PGF2α levels were observed in the 250 and 500 mg/kg sulfasalazine groups compared with the saline group (P<0.05, P<0.001, respectively). SOD increased significantly in both sulfasalazine groups compared with the PTZ+saline group (P<0.05). Our study demonstrated that sulfasalazine had protective effects on PTZ-induced convulsions by protecting against oxidative and inflammatory damage associated with PTZ.

Antioxidative effects of uridine in a neonatal rat model of hyperoxic brain injury

Premature birth is a major problem that results in an increased risk of mortality and morbidity. The management of such infants consists of supraphysiological oxygen therapy, which affects brain development due, in part, to the deterioration caused by reactive oxygen species (ROS). We showed previously that exogenously administered uridine provides neuroprotection in a neonatal rat model of hyperoxic brain injury. Hence, the aim of the present study was to investigate the effects of uridine on ROS in the same setting. Hyperoxic brain injury was induced by subjecting a total of 53 six-day-old rat pups to 80% oxygen (the hyperoxia group) for a period of 48 h. The pups in the normoxia group continued breathing room air (21% oxygen). Normoxia + saline or hyperoxia + saline or hyperoxia + uridine 100 mg/kg or hyperoxia + uridine 300 mg/kg or hyperoxia + uridine 500 mg/kg was injected intraperitoneally (i. p.) 15 min prior to the hyperoxia procedure. The pups were decapitated and the brains were homogenized to analyze superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), and malondialdehyde (MDA) enzymes as well as DJ-1 (protein deglycase DJ-1) — an oxidative stress-sensitive protein. Hyperoxia-induced may cause overproduction of oxygen radicals and the oxidant/antioxidant balance may be disturbed in the brain. Brain MPO and MDA levels were significantly increased in saline-receiving pups exposed to hyperoxia. Brain SOD and GSH-Px levels were significantly decreased in saline-receiving pups exposed to hyperoxia. Our results showed that uridine administration prevented the hyperoxia-induced decrease in SOD and GSH-Px while counteracting the hyperoxia-induced increase in MPO and MDA in a dose-dependent manner. Uridine also increased the DJ-1 levels in brains of rat pups subjected to hyperoxia. These data suggest that uridine exhibits antioxidative properties which may mediate the protective effects of uridine in a neonatal rat model of hyperoxic brain injury.

Evaluation of antioxidant and antidepressant activity of hydro-alcoholic extract of Ximenia americana stem bark

The present study was undertaken to evaluate the antioxidant and antidepressant activity of hydroalcoholic extract of Ximenia americana in case of Sodium fluoride induced toxicity on ICR mices. Antioxidant activity of the plant was evaluated in vitro through 2,2’-Azobis (2-Amidino-propane) Dihydrochloride test, metal chelating assay and total antioxidant capacity and in vivo through evaluation of malondialdehyde content in brain and liver. Antidepressant activity was evaluated through tail suspension test. In vitro evaluation of antioxidant activity showed that hydro-alcoholic extract of stem bark of Ximenia americana possesses a total antioxidant capacity of 303.081 ± 4.946 mg equivalent ascorbic acid per gram. From 2, 2’-Azobis (2-Amidino-propane) Dihydrochloride and metal chelating tests, it emerged that the extract inhibits hemolysis and chelates metals concentration-dependent manner. Animals were randomly divided into four groups with five animals in each group. The control group received distilled water, group II received sodium fluoride at dose of 13.6 mg/kg body weight, group III and group VI: received respectively hydro-alcoholic extract of Ximenia americana at 250 mg/kg and 500 mg/kg with sodium fluoride during 7 days. Results showed sodium fluoride decrease animal’s body weight even at the presence of the extract, increased significantly animal’s inactivity time and malondialdehyde levels in liver and brain. Animal’s inactivity time and malondialdehyde levels were significantly improved at the presence of the hydro-alcoholic extract of Ximenia americana. Ximenia americana have potential to mitigate sodium fluoride toxicity.

Stressor and Multi‐Organ Antioxidant Profile following Early Life Maternal Deprivation in Albino Rats

One‐week‐old albino pups were separated from their dams for a period of 24 to 48 hours. Sixty (60) rats were divided into 6 equal groups (n=10). Group A rats were separated for 24 hours and given glucose subcutaneously (200mg/kg) at 2, 7, 12 and 22 hours post maternal deprivation (MD). Group B rats received no intervention or treatment. Group C was subjected to 24 hours MD and given distilled water at regular intervals as group A. Group D rats had no MD but were given distilled water at same intervals as group A. Groups E and F were subjected to 48‐hour MD and administered Glucose or distilled water respectively at 2, 7, 17, 22, 27, 32, 42 and 47 hours post MD. Blood and tissue samples were collected for biochemical analyses.Significant weight gains were recorded in the groups with no maternal deprivation. The 48‐hour MD group supplemented with glucose competed favorably, showing a 7.2% weight gain over two days. At the other end of the spectrum, the 24‐hour MD supplemented with distilled water group recorded a 3% weight loss.The results show a graded rise in brain total protein values with time, with the highest values recorded in the 48‐hour MD + distilled water group and the lowest in the 24‐hour MD + distilled water group. Other organs showed no significant differences between groups. There were no differences across groups in all the organs assayed for nitric oxide (NO) either. For specific oxidative stress markers, Brain malondialdehyde (MDA) levels appear to be significantly lowest at the 48‐hour MD + distilled water group when compared with other groups. This correlated with a time dependent depletion in the brain antioxidant enzyme profiles studied. Brain GST, GPX and SOD all show highest concentrations in the 24‐hour MD + glucose group with lowest values recorded in the 48‐hour MD + distilled water group. Other organs did not show marked differences in between groups.Cortisol levels were assayed to evaluate stressor responses. The highest concentrations were seen in the 48‐hour MD + glucose group with the least seen in the 24‐hour MD + distilled water group. Consequently, parenteral administration of fluids (water and glucose) are a poor substitute for maternal nutrition although initial evidence points towards potential decline in brain antioxidant profile.Support or Funding InformationThe Tertiary Education Trust Fund (TETFUND) of Nigeria. The Faculty of Veterinary Medicine, University of Abuja, Nigeria.The Cardiorenal research group, Faculty of Veterinary Medicine, University of Ibadan; especially Professor Adeolu A. Adedapo, Dr. Tayo O. Omobowale, Dr. Ademola A. Oyagbemi and Dr. Jerry Afolabi.Brain Total Protein (TP) and Malondialdehyde (MDA) charts of all the groupsFigure 1

Effects of fullerene C60 supplementation on gut microbiota and glucose and lipid homeostasis in rats

The effects of twelve weeks of supplementation with fullerene C60 olive/coconut oil solution on a broad spectrum of parameters in rats were examined. The tissue bioaccumulation of C60 was shown to be tissue-specific, with the liver, heart, and adrenal glands being the organs of the greatest, and the kidney, brain, and spleen being the organs of the smallest accumulation. C60 did not change aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase serum activities level, nor the damage of liver cells DNA. There were no effects of fullerene on prooxidant-antioxidant balance in the liver, kidney, spleen, heart, and brain, nor any visible harmful effects on the liver, heart, aorta, spleen, kidney, and small intestine histology. Fullerene changed the gut microbiota structure towards the bacteria that ameliorate lipid homeostasis, causing a serum triglycerides concentration decrease. However, C60 significantly increased the insulin resistance, serum ascorbate oxidation, and brain malondialdehyde and advanced oxidation protein products level. The deteriorative effects of C60 on the brain and serum could be attributed to the specific physicochemical composition of these tissues, potentiating the C60 aggregation or biotransformation as the key element of its pro-oxidative action.

Capsaicin Exerts Anti-convulsant and Neuroprotective Effects in Pentylenetetrazole-Induced Seizures.

The transient receptor potential vanilloid-1 (TRPV1) receptor has been implicated in the development of epileptic seizures. We examined the effect of the TRPV1 agonist capsaicin on epileptic seizures, neuronal injury and oxidative stress in a model of status epilepticus induced in the rat by intraperitoneal (i.p.) injections of pentylenetetrazole (PTZ). Capsaicin was i.p. given at 1 or 2 mg/kg, 30 min before the first PTZ injection. Other groups were i.p. treated with the vehicle or the anti-epileptic drug phenytoin (30 mg/kg) alone or co-administered with capsaicin at 2 mg/kg. Brain levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, and paraoxonase-1 (PON-1) activity, seizure scores, latency time and PTZ dose required to reach status epilepticus were determined. Histopathological assessment of neuronal damage was done. Results showed that brain MDA decreased by treatment with capsaicin, phenytoin or capsaicin/phenytoin. Nitric oxide decreased by capsaicin or capsaicin/phenytoin. GSH and PON-1 activity increased after capsaicin, phenytoin or capsaicin/phenytoin. Mean total seizure score decreased by 48.8% and 66.3% by capsaicin compared with 78.7% for phenytoin and 69.8% for capsaicin/phenytoin treatment. Only phenytoin increased the latency (115.7%) and threshold dose of PTZ (78.3%). Capsaicin did not decrease the anti-convulsive effect of phenytoin but prevented the phenytoin-induced increase in latency time and threshold dose. Neuronal damage decreased by phenytoin or capsaicin at 2 mg/kg but almost completely prevented by capsaicin/phenytoin. Thus in this model of status epilepticus, capsaicin decreased brain oxidative stress, the severity of seizures and neuronal injury and its co-administration with phenytoin afforded neuronal protection.

Effect of fentanyl and its three novel analogues on biochemical, oxidative, histological, and neuroadaptive markers after sub-acute exposure in mice

AimsComparative sub-acute toxicity, including tolerance and dependence potential of fentanyl and its three novel and potent analogues was determined in mice. Main methodsComparative sub-acute (21 d, intraperitoneal; 1/10 LD50) toxicity of fentanyl and its three novel analogues viz., N-(1-(2-phenoxyethyl)-4-piperidinyl) propionanilide (2), N-isopropyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (5), and N-t-butyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (6) was determined in mice. Animals were observed for additional seven days to assess the recovery. The brain, liver and kidney toxicity was assessed on the basis of various biochemical, oxidative, histological, and neuroadaptive markers. The expression levels of key neuronal markers associated with drug tolerance and dependence were investigated by western blot and immunohistochemistry. Key findingsFentanyl and its analogues caused abnormal levels of liver and kidney specific biomarkers in plasma. Brain malondialdehyde (MDA) levels were raised by all the treatments and kidney MDA level by analogue 6 (21 d). Reduced glutathione levels in brain, liver, and kidney were diminished by all the treatments (21 & 28 d) and a significant change in the levels of antioxidant enzymes was also produced mainly after 21 d. The deleterious effects of fentanyl and its analogues were further substantiated by corresponding histopathological changes in brain, liver and kidney (21 & 28 d). These compounds were also found to produce neuroadaptive changes as evidenced by the increased expression levels of c-Fos, glucocorticoid receptor, N-methyl-d-aspartate receptor1 and μ-opioid receptor (21 & 28 d). SignificanceThree novel analogues of fentanyl were envisaged to have alternative therapeutic potentials. However, their comparative sub-acute toxicity revealed undesirable side effects, thereby masking their therapeutic ability.

Diosmetin Mitigates Cognitive and Memory Impairment Provoked by Chronic Unpredictable Mild Stress in Mice.

Materials and Methods In the present experimental study, male NMRI mice were exposed to chronic unpredictable mild stress (CUMS) paradigm for 35 days. Diosmetin (at doses of 10, 20, and 40 mg/kg. i.p.) or diosmetin solvent (normal saline + DMSO, 1 ml/kg; i.p.) was administered 30 min before stress induction. After 28 days, memory and cognitive performance were assessed by shuttle box and novel object recognition tests. Finally, antioxidant capacity (FRAP) and malondialdehyde (MDA) level of serum and brain, and serum corticosterone level were evaluated. Results Behavioral tests showed that CUMS significantly reduced the secondary latency in passive avoidance memory test and diagnosis index in novel object recognition test compared to the control group (P < 0.001), whereas treatment with diosmetin (20 and 40 mg/kg) significantly improved memory performance in the two tests (P < 0.001). In addition, diosmetin (40 mg/kg) could pronouncedly suppress increase in serum corticosterone levels, reduction in antioxidant capacity, and production of excess MDA caused by CUMS compared to the control group (P < 0.01, P < 0.001, and P < 0.001, respectively). Conclusion Chronic stress can impair memory and cognition and treatment with diosmetin can partly improve this disorder in male mice by increasing the antioxidant capacity of brain tissue and serum and improving serum corticosterone levels.

Electromagnetic Waves from Mobile Phones may Affect Rat Brain During Development.

To investigate the effects of electromagnetic waves (EMWs) from mobile phones (MPs) on rat brains of rats by morphological and biochemical analysis. EMW was applied for two hours/day until birth in stand-by fetal and EMW fetal groups and postnatal 60 < sup > th < /sup > day in stand-by and EMW groups. The control group was not exposed to MP. On postnatal 60 < sup > th < /sup > day, brain malondialdehyde (MDA) and glutathione (GSH) levels were measured, and western blot analysis was performed to determine glial fibrillary acidic protein (GFAP) content. Hematoxylin and eosin staining and GFAP immunohistochemistry were applied. Trigeminal nerves were examined using the transmission electron microscope. In comparison to controls, rats exposed to MP in stand-by or talk modes had significantly increased neuronal damage in the cortex and hippocampus. Increased MDA levels in the EMW group and decreased GSH levels in the stand-by, EMW fetal and EMW groups were found compared with controls. Increased GFAP content in the EMW group and increased GFAP staining in the EMW fetal and EMW groups compared to controls were observed. EMW group had a significantly decreased number of myelinated axons than control animals. The results of this study suggests that 1800 MHz EMWs (SAR=1.79 W/kg) exposure in the prenatal and early postnatal life may lead to trigeminal nerve damage in addition to oxidative stress-induced neuronal degeneration and astroglial activation in the rat brain. Effects seem to be mode related, being more detrimental in groups exposed to MP during talk mode.

The Changes of Brain Edema and Neurological Outcome, and the Probable Mechanisms in Diffuse Traumatic Brain Injury Induced in Rats with the History of Exercise.

Since no definitive treatment has been suggested for diffuse traumatic brain injury (TBI), and also as the effect of exercise has been proven to be beneficial in neurodegenerative diseases, the effect of endurance exercise on the complications of TBI along with its possible neuroprotective mechanism was investigated in this study. Our objective was to find out whether previous endurance exercise influences brain edema and neurological outcome in TBI. We also assessed the probable mechanism of endurance exercise effect in TBI. Rats were randomly assigned into four groups of sham, TBI, exercise + sham and exercise + TBI. Endurance exercise was carried out before TBI. Brain edema was assessed by calculating the percentage of brain water content 24h after the surgery. Neurological outcome was evaluated by obtaining veterinary coma scale (VCS) at - 1, 1, 4 and 24h after the surgery. Interleukin-1β (IL-1β), total antioxidant capacity (TAC), malondialdehyde (MDA), protein carbonyl and histopathological changes were evaluated 24h after the surgery. Previous exercise prevented the increase in brain water content, MDA level, histopathological edema and apoptosis following TBI. The reduction in VCS in exercise + TBI group was lower than that of TBI group. In addition, a decrease in the level of serum IL-1β and the content of brain protein carbonyl was reported in exercise + TBI group in comparison with the TBI group. We suggest that the previous endurance exercise prevents brain edema and improves neurological outcome following diffuse TBI, probably by reducing apoptosis, inflammation and oxidative stress.

Inhibition of oxidative stress by testosterone improves synaptic plasticity in senescence accelerated mice

ABSTRACTIt is well known that synaptic plasticity is associated with cognitive performance in Alzheimer’s disease (AD). Testosterone (T) is known to exert protective effects on cognitive deficits in AD, but the underlying mechanisms of androgenic action on synaptic plasticity remain unclear. Thus, the aim of this study was to examine the protective mechanism attributed to T on synaptic plasticity in an AD senescence accelerated mouse prone 8 (SAMP8) model. The following parameters were measured: (1) number of intact pyramidal cells in hippocampal CA1 region (2) phosphorylated N-methyl-D-aspartate receptor-1 (p-NMDAR1) and (3) phosphorylated calmodulin-dependent protein kinase II (p-CaMKII). In addition, the content of whole brain malondialdehyde (MDA) as well as activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined. Treatment with T significantly elevated the number of intact pyramidal cells in hippocampal CA1 region and markedly increased hippocampal protein and mRNA expression levels of p-NMDAR1 and p-CaMK II. Further, T significantly decreased whole brain MDA levels accompanied by elevated activities of SOD and GSH-Px. Data suggest that the protective effects of T on synaptic plasticity in a mouse AD model may be associated with reduction of oxidant stress.

Protective effects of vitamin D on neurophysiologic alterations in brain aging: role of brain-derived neurotrophic factor (BDNF)

ABSTRACT Background/aim: Vitamin D has been hypothesized to be main regulator of the aging rate, alongside evidences support its role in neuroprotection. However, data about the protective role of vitamin D against neurophysiologic alterations associated with brain aging is limited. This study investigated the possible protective effects that vitamin D has on brain-derived neurotrophic factor (BDNF), cholinergic function, oxidative stress and apoptosis in aging rat brain. Methods: Male Wister albino rats aged 5 months (young), 12 months (middle aged) and 24 months (old) (n = 20 each) were used. Each age group subdivided to either vitamin D3 supplementation (500 IU/kg/day orally for 5 weeks) or no supplementation (control) group (n = 10 each). Serum 25-hydroxyvitamin D [25(OH)D], brain BDNF and malondialdehyde levels and activities of acetylcholinesterase (AChE), antioxidant enzymes (glutathione reductase, glutathione peroxidase and superoxide dismutase) and caspase-3 were quantified. Results: Vitamin D supplementation significantly mitigated the observed aging-related reduction in brain BDNF level and activities of AChE and antioxidant enzymes and elevation in malondialdehyde level and caspase-3 activity compared to control groups. Brain BDNF level correlated positively with serum 25(OH) D level and brain AChE activity and negatively with brain malondialdehyde level and caspase-3 activity in supplemented groups. Conclusion: Restoring vitamin D levels may, therefore, represent a useful strategy for healthy brain aging. Augmenting brain BDNF seems to be a key mechanism through which vitamin D counteracts age-related brain dysfunction.

Anti-glycation, anti-hemolysis, and ORAC activities of demethylcurcumin and tetrahydroxycurcumin in vitro and reductions of oxidative stress in d-galactose-induced BALB/c mice in vivo

BackgroundThere were few report concerning anti-glycation and antioxidant activities of the minor amounts of components in curcuminoids, demethylcurcumin and tetrahydroxycurcumin, in vitro and in vivo.ResultsThe bovine serum albumin/galactose of non-enzymatic glycation models, radical-induced hemolysis, and oxygen radical absorbance capacity (ORAC) were studied in vitro, and the d-galactose-induced oxidative stress in BALB/c mice and then demethylcurcumin or tetrahydroxycurcumin interventions in vivo. The parameters of oxidative stress in plasma and brain extracts were determined among animal groups with or without both curcuminoids interventions. The demethylcurcumin and tetrahydroxycurcumin exhibited anti-glycation, anti-hemolysis, and ORAC activities, and showed much better and significant difference (P < 0.05) compared to those of curcumin in vitro. In animal experiments, the intervened two curcuminoids at both concentrations showed to lower serum malondialdehyde (MDA), brain MDA levels and iNOS protein expressions, and elevate serum ORAC activities, and showed difference (P < 0.05) compared to the galactose-induced control.ConclusionThe demethylcurcumin and tetrahydroxycurcumin showed potentials in developing functional foods for antioxidant-related purposes.