Oxidative Damage In Brain Research Articles

Loss of Nucleobindin-2/Nesfatin-1 increases lipopolysaccharide-induced murine acute lung inflammation.

NUCB2/nesfatin-1 is expressed in variety of tissues. Treatment with nesfatin-1 reduces inflammation in rat models of subarachnoid hemorrhage-induced oxidative brain damage and traumatic brain injury as well as myocardial injury. There is only one study showing anti-inflammatory actions of nesfatin-1 on acute lung inflammation. To more precisely determine the role of NUCB2/nesfatin-1 in acute lung inflammation, we conducted a study using NUCB2/nesfatin-1 knockout (NKO) mice as well as neutrophils isolated from the bone marrows of WT and NKO mice. Our findings suggest that the absence of NUCB2/nesfatin-1 significantly increases the accumulation of adherent neutrophils by approximately 3 times compared with WT within LPS-treated lungs. Integrating this with observations from both BALF and neutrophil cytokine expression, we propose that although neutrophils lacking NUCB2/nesfatin-1 individually secrete less pro-inflammatory cytokines compared with stimulated WT cells, the result of knocking out NUCB2/nesfatin-1 is net pro-inflammatory. No change was found in NUCB2/nesfatin-1 mRNA or protein expression comparing WT LPS and PBS-treated samples. Taken together, our results show that NUCB2/nesfatin-1 is constitutively expressed in mouse lungs and neutrophils and demonstrates anti-inflammatory properties in mouse lungs during acute lung injury, by inhibiting adherent neutrophil accumulation and inflammatory cytokine expression.

Effect of Piracetam on Brain Oxidative Stress and Tissue Damage Following Toluene Exposure in Rats

In this study, the effect of the nootropic drug piracetam on brain oxidative stress and histopathological changes in brain, liver and kidney following exposure to toluene in rats was examined. Piracetam (150 or 300 mg/kg, subcutaneously, daily) was given along with toluene (500 mg/kg, intraperitoneally, daily) for one week. The brain content of malondialdehyde (MDA), reduced glutathione (GSH) and the activity of paraoxonase-1 (PON-1), and butyrylcholinesterase (BChE) in brain homogenates were determined. Histopathology of the brain, liver and kidney and brain Bax immunohistochemistry were performed. Results showed that exposure to toluene resulted in increased brain lipid peroxidation (MDA) and NO along with decreased reduced glutathione. Toluene also inhibited PON-1, and BChE activities. The administration of piracetam had no significant effect on brain lipid peroxidation. The level of reduced glutathione was unchanged by piracetam but PON1 activity was increased by the lower dose of the drug. Piracetam showed no significant effect on BChE activity in toluene treated rats. Histopathological examination of the brain of toluene only treated rats showed degenerated neurons in cerebral cortex, marked neuronal vacuolation in hippocampus and focal hemorrhage. Bax 3 immunohistochemical staining showed cytoplasmic reactivity in degenerated neurons. Rats given piracetam showed decreased cortical cellularity, increased number of degenerated neurons and increased BAX staining. The higher dose of the drug caused sinusoidal hemorrhage and intertubular hemorrhage in kidney. Collectively, these results indicate that treatment with piracetam wan not able to decrease neuronal damage in rats exposed to toluene.

Phytol suppresses parasitemia and ameliorates anaemia and oxidative brain damage in mice infected with Plasmodium berghei

The quest for the development of a novel antimalarial drug informed the decision to subject phytol to in vivo trials following a demonstration of therapeutic potential against chloroquine sensitive strain of Plasmodium falciparum under in vitro condition. On this basis, the in vivo anti-Plasmodium berghei activity of phytol including the ameliorative effects of the compound on P. berghei-associated anaemia and organ damage were investigated. Mice were infected with chloroquine-sensitive strain of P. berghei and were treated with phytol at a dose of 10 and 20 mg/kg body weight (BW) for four days. The levels of parasitemia, packed cell volume and redox sensitive biomarkers of liver, brain and spleen tissues were determined. Our result revealed that phytol significantly (p < 0.05) suppressed the multiplication of P. berghei in a dose-dependent manner. Additionally, the phytol significantly (p < 0.05) ameliorated the P. berghei-induced anaemia and brain damage. Data from the present study demonstrated that phytol has suppressive effect on P. berghei and could ameliorate some P. berghei-induced pathological changes.

N-acetylcysteine-amide improves tissue oxidative stress, DNA damage, and proteins disappearance in methamphetamine toxicity more efficiently than N-acetyl-L-cysteine

The aim of the present study is to discover a new protective agent to protect against oxidative stress, DNA damage, and proteins disappearance in brain, liver, and kidney in methamphetamine (METH) abusers. Forty male albino rats were divided into 4 equal groups: (1) Control, (2) METH, (3) N-acetyl-L-cysteine (NAC, 500 mg/kg body weight (bwt)) + METH, (4) N-acetylcysteine-amide (NACA, 250 mg/kg (bwt)) + METH. Group 1 was injected (i.p) with saline (1 ml/kg bwt) while groups 2,3 & 4 were injected (i.p) with 4 injections with METH (10 mg/kg bwt) every 2 hours over an 8-hour period. NAC and NACA were injected 30 minutes before METH injections. Reduced glutathione (GSH), glutathione peroxidase (GPx), lipid peroxidation (MDA), catalase (CAT), and protein carbonyl levels were measured in the brain, liver, and kidney tissues. The DNA and protein contents of brain, liver, and kidney tissues were also detected. The results indicated that METH induced oxidative cell stress by increasing MDA while decreasing cell GSH and the antioxidant enzymes such as CAT and GPx levels. METH induced DNA damage and proteins disappearance in brain, liver and kidney tissues. NAC or NACA injection before METH injection prevented oxidative stress, DNA damage, and proteins disappearance in brain, liver and kidney of METH-injected rats and NACA was more effective than NAC in treated animals. NACA was more effective than NAC in treated animals through preventing tissue oxidative stress, DNA damage, and proteins disappearance in METH toxicity than NAC.

Paraoxonase-1 and -3 Protein Expression in the Brain of the Tg2576 Mouse Model of Alzheimer's Disease.

Background: Brain oxidative lipid damage and inflammation are common in neurodegenerative diseases such as Alzheimer’s disease (AD). Paraoxonase-1 and -3 (PON1 and PON3) protein expression was demonstrated in tissue with no PON1 or PON3 gene expression. In the present study, we examine differences in PON1 and PON3 protein expression in the brain of a mouse model of AD. Methods: we used peroxidase- and fluorescence-based immunohistochemistry in five brain regions (olfactory bulb, forebrain, posterior midbrain, hindbrain and cerebellum) of transgenic (Tg2576) mice with the Swedish mutation (KM670/671NL) responsible for a familial form of AD and corresponding wild-type mice. Results: We found intense PON1 and PON3-positive staining in star-shaped cells surrounding Aβ plaques in all the studied Tg2576 mouse-brain regions. Although we could not colocalize PON1 and PON3 with astrocytes (star-shaped cells in the brain), we found some PON3 colocalization with microglia. Conclusions: These results suggest that (1) PON1 and PON3 cross the blood–brain barrier in discoidal high-density lipoproteins (HDLs) and are transferred to specific brain-cell types; and (2) PON1 and PON3 play an important role in preventing oxidative stress and lipid peroxidation in particular brain-cell types (likely to be glial cells) in AD pathology and potentially in other neurodegenerative diseases as well.

Preliminary results of PBA-loaded nanoparticles development and the effect on oxidative stress and neuroinflammation in rats submitted to a chemically induced chronic model of MSUD.

Maple syrup urine disease (MSUD) is a genetic disorder that leads the accumulation of branched-chain amino acids (BCAA) leucine (Leu), isoleucine, valine and metabolites. The symptomatology includes psychomotor delay and mental retardation. MSUD therapy comprises a lifelong protein strict diet with low BCAA levels and is well established that high concentrations of Leu and/or its ketoacid are associated with neurological symptoms. Recently, it was demonstrated that the phenylbutyrate (PBA) have the ability to decrease BCAA concentrations. This work aimed the development of lipid-based nanoparticles loaded with PBA, capable of targeting to the central nervous system in order to verify its action mechanisms on oxidative stress and cell death in brain of rats subjected to a MSUD chronic model. PBA-loaded nanoparticles treatment was effective in significantly decreasing BCAA concentration in plasma and Leu in the cerebral cortex of MSUD animals. Furthermore, PBA modulate the activity of catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase enzymes, as well as preventing the oxidative damage to lipid membranes and proteins. PBA was also able to decrease the glial fibrillary acidic protein concentrations and partially decreased the reactive species production and caspase-3 activity in MSUD rats. Taken together, the data indicate that the PBA-loaded nanoparticles could be an efficient adjuvant in the MSUD therapy, protecting against oxidative brain damage and neuroinflammation.

Protective effect of resveratrol on citrullinemia type I-induced brain oxidative damage in male rats.

Citrullinemia Type I is an inborn error, which leads to accumulation of citrulline and ammonia in blood and body tissues. We evaluated the in vitro effects of citrulline, ammonia and the influence of resveratrol on oxidative stress parameters in the cerebrum of 30- and 60-day-old male Wistar rats. Citrulline (0.1, 2.5, 5.0mM), ammonia (0.01, 0.1, 1.0mM) and resveratrol (0.01, 0.1, 0.5mM) were added to the assays to measure thiobarbituric acid reactive substances (TBA-RS), total sulfhydryl content and the activity of antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Citrulline (2.5 and 5.0mM) increased TBA-RS in the cerebellum of 30-day-old and in the cerebral cortex and cerebellum of 60-day-old. Citrulline (5.0mM) increased SOD and reduced GSH-Px in the hippocampus of 30-day-old, whereas in the cerebellum it increased GSH-Px. In the cerebral cortex, 2.5 and 5.0mM citrulline reduced GSH-Px. In 60-day-old, 2.5 and 5.0mM citrulline increased SOD in the cerebellum, increased GSH-Px in the cerebral cortex and 5.0mM citrulline reduced CAT and increased SOD in the cerebral cortex. Ammonia (0.1 and 1.0mM) reduced the sulfhydryl content in the cerebral cortex of 30- and 60-day-old, 1.0mM ammonia increased SOD and reduced GSH-Px in the cerebellum of 30-day-old and increased SOD in the hippocampus and cerebellum of 60-day-old. Resveratrol was able to prevent the majority of these alterations. Thus, citrulline and ammonia induce oxidative stress in the cerebrum of rats; however, resveratrol was able to exert antioxidant effects against these substances.

The Protective Action of Rubus sp. Fruit Extract Against Oxidative Damage in Mice Exposed to Lipopolysaccharide.

Neuroinflammation is an event that occurs in several pathologies of brain. Rubus sp. (blackberry) is a powerful antioxidant fruit, and its extract has neuroprotective activity. The aim of this study was to investigate the blackberry extract properties on lipopolysaccharide (LPS)-induced neuroinflammation, in relation to oxidative parameters and acetylcholinesterase activity in the brain structures of mice. We also investigated interleukin-10 levels in serum. Mice were submitted to Rubus sp. extract treatment once daily for 14days. On the fifteenth day, LPS was injected in a single dose. LPS induced oxidative brain damage and the blackberry extract demonstrated preventive effects in LPS-challenged mice. LPS administration increased reactive oxygen species levels in the cerebral cortex and striatum, as well as lipid peroxidation in the cerebral cortex. However, the blackberry extract prevented all these parameters. Furthermore, LPS decreased thiol content in the striatum and hippocampus, while a neuroprotective effect of blackberry extract treatment was observed in relation to this parameter. The blackberry extract also prevented a decrease in catalase activity in all the brain structures and of superoxide dismutase in the striatum. An increase in acetylcholinesterase activity was detected in the cerebral cortex in the LPS group, but this activity was decreased in the Rubus sp. extract group. Serum IL-10 levels were reduced by LPS, and the extract was not able to prevent this change. Finally, we observed an antioxidant effect of blackberry extract in LPS-challenged mice suggesting that this anthocyanin-rich extract could be considered as a potential nutritional therapeutic agent for preventive damage associated with neuroinflammation.

Effect of Lepidium meyenii (maca) on spatial memory and brain oxidative damage of ovariectomized-rats exposed to mobile phone

Background: Oxidative stress, genetic expression changes, and decomposition of the blood-brain barrier have been shown to be caused by exposure to radiofrequency radiation (RFR); therefore, the search for drugs or food products that offer some protection from these effects has attracted interest. Lepidium meyenii (maca) is a native Andean plant known for its effects on the female reproductive system as well as its immunomodulating, energizing, antioxidant, and nutritive properties due to its high concentration of alkaloids, amino acids, glucosinolates, fatty acids, and macamides. Objectives: We aim to determine the effect of dietary maca supplementation on spatial memory and cerebral oxidative damage in rats with induced menopause and/or with exposure to mobile phone radiation. Method: Female rats divided into 6 groups (six rats in each group): control or not ovariectomized (O-), ovariectomized (O+), ovariectomized + estrogen (O+E+), ovariectomized + estrogen + irradiated (O+E+I+), ovariectomized + maca (O+M+), and ovariectomized + maca + irradiated (O+M+I). Rat spatial memory was tested using the Morris water navigation task. Rats were sacrificed, and cerebral malondialdehyde was measured. Results: After exposure to mobile phone radiation, the group supplemented with maca showed improved spatial memory and lower levels of malondialdehyde than the estrogenized group. Conclusions: Our results suggest that consumption of maca has a positive effect on the maintenance of memory and decreases oxidative stress caused by mobile phone radiation. However, it is necessary to extend this work using a larger sample size.

Gallic acid protects cerebral cortex, hippocampus, and striatum against oxidative damage and cholinergic dysfunction in an experimental model of manic-like behavior: Comparison with lithium effects.

Bipolar disorder is characterized by episodes of depression and mania, and oxidative stress has been associated with the observed neurochemical changes in this disease. We evaluated the effects of gallic acid on hyperlocomotion, acetylcholinesterase activity, and oxidative stress in an animal model of ketamine-induced mania. Rats were pretreated orally with vehicle, gallic acid (50 or 100mg/kg), or lithium (45mg/kg twice a day) for 14days. Between days 8 and 14, the animals also received ketamine (25mg/kg) or saline daily. On the 15th day, hyperlocomotion was assessed, following which the animals were euthanized, and brains were collected. Results showed that ketamine-induced hyperlocomotion and caused oxidative damage by increasing reactive oxygen species levels, lipid peroxidation, and nitrite levels, and decreasing the total thiol content and the activities of catalase, superoxide dismutase, and glutathione peroxidase in the brain. Pretreatment with gallic acid and lithium prevented hyperlocomotion and brain oxidative damage. Further, ketamine increased the acetylcholinesterase activity in the hippocampus and striatum, whereas gallic acid and lithium ameliorated this alteration. Thus, gallic acid may provide effective protection against manic-like behavior by reducing oxidative stress and preventing cholinergic signaling dysfunction in the brain regions involved in emotion regulation.

Neuroprotective potential of hydroethanolic hull extract of Juglans regia L. on isoprenaline induced oxidative damage in brain of Wistar rats.

The study was aimed at assessing isoprenaline (ISO) induced oxidative damage in brain of Wistar rats and its protection by hydroethanolic hull extract of Juglans regia. Administration of ISO significantly increases catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), malondialdehyde (MDA) and advanced oxidation protein product (AOPP) levels and significantly reduced activities of antioxidant status (TAS), total thiols (TTH), acetylcholinesterase (AChE), arylesterase (AE), and glutathione peroxidase (GPx) in rat brain. Histopathologically, neuronal degeneration, spongiosis and gliosis were seen in cerebral cortex after ISO administration. Pretreatment with hull extract restored TAS, TTH, AChE, CAT and SOD values. Additionally, significant reductions were noted in levels of MDA, AOPP, and severity of histomorphological changes in cerebral cortex following hull extract treatment. Altered antioxidant biomarkers along with histopathological changes indicate oxidative injury in rat brain following ISO administration. Repeated administration of J. regia hull extract demonstrating presence of neuroprotective properties against ISO induced oxidative damage in rat brain.

Thymoquinone Improved Lead-Induced DNA Damage and Oxidative Stress in Rat Brain

Lead (Pb) is a pervasive industrial and environmental pollutant that seriously impairs the central nervous system, primarily by disrupting the redox balance. The current research was conducted to explore the possible beneficial action of thymoquinone (TQ), the main active component in Nigella sativa seed volatile oil, against brain oxidative stress and DNA damage caused by Pb. Wistar adult male rats were treated with TQ (5 mg/kg/day, per os) and/or Pb (2000 ppm of Pb acetate in drinking water) for five weeks. Results showed that Pb exposure significantly increased metal content, malondialdehyde concentration and DNA damage (assessed by comet assay), but significantly decreased the level of reduced glutathione and the activities of catalase, glutathione peroxidase, and superoxide dismutase in the brain tissue. These detrimental effects Pb-induced, except tissue metal accumulation, were significantly improved by TQ supplementation. In conclusion, our findings suggested that TQ might be a promising therapeutic alternative in Pb neurotoxicity.

RETRACTED: Tranilast ameliorated subchronic silver nanoparticles-induced cerebral toxicity in rats: Effect on TLR4/NLRP3 and Nrf-2

Silver nanoparticles (AgNPs) are widely applied in various aspects of life. However, recent studies reported their potential toxicity both on environment and human health. The present study aimed to unravel the underlying molecular mechanisms involved in AgNPs-induced brain toxicity. Moreover, chemopreventive effect of tranilast, an analogue of tryptophan metabolite and a mast cell membrane stabilizer was evaluated. Thirty Sprague Dawley rats were enrolled equally into Normal control group, AgNPs-intoxicated group (50 mg/kg, 3 times/week) and tranilast (300 mg/kg, 3 times/week)+AgNPs group. AgNPs administration triggered brain oxidative stress as depicted by reduced Nrf-2 expression, decreased TAC and GSH as well as upregulated brain lipid peroxidation. The apparent brain oxidative damage was accompanied by elevated levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α). Moreover, brain levels of TLR4, NLRP3 and caspase-1 were up-regulated. Additionally, histological study indicated marked cellular injury in cerebrum and cerebellum specimens. This was concomitant with elevated serum CK activity and CK-BB level. On the other hand, tanilast administration remarkably alleviated AgNPs-induced brain toxicity. The present study shed the light on implication of TLR4/NLRP3 axis and NrF2 in AgNPs-induced brain toxicity. In addition, it explored the potential protective effect of tranilast on AgNPs-induced brain injury via antioxidant and anti-inflammatory efficacies.

Sialylation acts as a checkpoint for innate immune responses in the central nervous system

Sialic acids are monosaccharides that normally terminate the glycan chains of cell surface glyco-proteins and -lipids in mammals, and are highly enriched in the central nervous tissue. Sialic acids are conjugated to proteins and lipids (termed "sialylation") by specific sialyltransferases, and are removed ("desialylation") by neuraminidases. Cell surface sialic acids are sensed by complement factor H (FH) to inhibit complement activation or by sialic acid-binding immunoglobulin-like lectin (SIGLEC) receptors to inhibit microglial activation, phagocytosis, and oxidative burst. In contrast, desialylation of cells enables binding of the opsonins C1, calreticulin, galectin-3, and collectins, stimulating phagocytosis of such cells. Hypersialylation is used by bacteria and cancers as camouflage to escape immune recognition, while polysialylation of neurons protects synapses and neurogenesis. Insufficient lysosomal cleavage of sialylated molecules can lead to lysosomal accumulation of lipids and aggregated proteins, which if excessive may be expelled into the extracellular space. On the other hand, desialylation of immune receptors can activate them or trigger removal of proteins. Loss of inhibitory SIGLECs or FH triggers reduced clearance of aggregates, oxidative brain damage and complement-mediated retinal damage. Thus, cell surface sialylation recognized by FH, SIGLEC, and other immune-related receptors acts as a major checkpoint inhibitor of innate immune responses in the central nervous system, while excessive cleavage of sialic acid residues and consequently removing this checkpoint inhibitor may trigger lipid accumulation, protein aggregation, inflammation, and neurodegeneration.

Proteomic analysis reveals plasma haptoglobin, interferon-γ, and interleukin-1β as potential biomarkers of pediatric refractory epilepsy

BackgroundChildren with refractory epilepsy (RE) are associated with increased mortality rate, nonfatal injuries, disability, and diminished quality of life. Biomarkers for the early prediction of RE is still an unmet need. MethodsEighteen children with RE and six age-matched unrelated controls were included in this study. Plasma samples were prefractionated by the optimized thermal treatment before proteomic analysis using 2DE-LC-MS/MS. Bioinformatic analysis was carried out using STRING protein network. Immunoassay of unprocessed plasma was applied to confirm changes of proteins of interest. P-value < 0.05 was considered statistically significant. ResultsProteomic analysis (n = 6 each group) revealed nine differentially expressed proteins, i.e., haptoglobin, S100A9, serpin B1, apolipoprotein A-I, apolipoprotein A-IV, apolipoprotein C-II, alpha-1-acid glycoprotein 1 and 2, and transthyretin. Western immunoblotting confirmed haptoglobin upregulation in the RE group. STRING protein network predicted the inflammatory cytokines, i.e., interferon gamma (IFN-γ), interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α), play roles in pathophysiology in RE patients. Cytokine immunoassay (n = 24, 18 RE vs. 6 controls) exhibited plasma IFN-γ was upregulated in RE patients as compared to the healthy individuals (median [IQR]; 2.9 [2.9, 4.9] vs. 1.32 [0.8, 1.5] pg/mL, p = 0.0013), and plasma IL-1β was significantly downregulated in patients (1.0 [0.2, 1.9] vs. 4.5 [1.9, 11.0] pg/mL, p = 0.01). TNF-α had no difference between groups. The results suggest that haptoglobin may be associated with oxidative brain damage, while IFN-γ and IL-1β may be involved with neuroinflammation. ConclusionsAlterations in plasma haptoglobin, IFN-γ, and IL-1β were associated with RE patients. Future studies using a combination of these candidate biomarkers may help predict the intractability of epilepsy in pediatric populations.

Neuroprotective effect of chrysin on isoniazid-induced neurotoxicity via suppression of oxidative stress, inflammation and apoptosis in rats

Isoniazid (INH) is among the most important anti-tuberculosis agents widely prescribed. However, its clinical use is restricted due to its severe side effects associated with neurotoxicity. The aim of the present study was to investigate the neuroprotective effects of chrysin (CR), a natural antioxidant, against INH-induced neurotoxicity in rats. The rats were treated orally with INH (400 mg/kg body weight) alone or with CR (25 and 50 mg/kg body weight) for 7 consecutive days. INH administration significantly increased brain lipid peroxidation and resulted in a significant decrease in antioxidant biomarkers including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH). INH treatment also increased levels of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), glial fibrillary acidic protein (GFAP) and activities of p38α mitogen-activated protein kinase (p38α MAPK) while decreasing levels of neural cell adhesion molecule (NCAM). Double immunofluorescence expressions of c-Jun N-terminal kinase (JNK) and Bcl-2 associated X protein (Bax) in brain tissues were increased after INH administration. Furthermore, INH increased mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO1), glutamate-cysteine ligase modifier subunit (Gclm), glutamate cysteine ligase catalytic subunit (Gclc), NF-κB, TNF-α, interleukin-1β (IL-1β), interleukin-6 (IL-6) and GFAP in rat brain tissues. Co-treatment with CR increased anti-oxidant capacity as well as regulated inflammation and apoptosis in brain. Additionally, molecular docking results showed that CR had the potential to interact with the active sites of TNF-α and NFκ-B. In conclusion, CR improved INH-induced brain oxidative damage, inflammation and apoptosis, possibly through their antioxidant properties.

Maternal Spirulina supplementation during pregnancy and lactation partially prevents oxidative stress, glial activation and neuronal damage in protein malnourished F1 progeny

Protein malnutrition (PMN) is a global health issue but most prevalent in Africa and Asia. It exerts detrimental effect on structural and physiological aspects of hippocampal circuitry. Despite accumulating evidence for PMN induced changes in nervous system, relatively very little is known about how maternal nutritional supplementation during malnutrition affects glial cells and neurons. Herein, we aimed to investigate the effects of maternal Spirulina supplementation against PMN induced oxidative stress, reactive gliosis and neuronal damage in hippocampus of F1 progeny. Three months old healthy Sprague Dawley females (n = 24) were shifted to normoprotein (NC; 20% protein) and low protein (LP; 8% protein) diets 15 days before conception. The NC and LP group females were subdivided into two groups according to Spirulina supplementation (400 mg/kg/b.wt. orally throughout gestation and lactation period): normal control with Spirulina (NC SPI) and low protein with Spirulina supplemented group (LP SPI). F1 progeny born were used in present study. Thus, building on earlier results of ameliorated neurobehavioral and cognitive abilities in Spirulina supplemented protein deprived rats, the present study incorporates neurochemical and morphometric analysis of glial cells and neurons and revealed that maternal Spirulina consumption partially prevented the PMN associated neuropathological alterations in terms of attenuated oxidative brain damage, reduced reactive gliosis and apoptotic cell population, improved dendritic branch complexity with few damaged neurons and enhanced mushroom shaped spine density. The results suggest that cellular changes in hippocampus after PMN are partially restored after maternal Spirulina supplementation and one could envision intervention approaches using Spirulina against malnutrition.

Spaceflight induces oxidative damage to blood-brain barrier integrity in a mouse model.

Many factors contribute to the health risks encountered by astronauts on missions outside Earth’s atmosphere. Spaceflight-induced potential adverse neurovascular damage and late neurodegeneration are a chief concern. The goal of the present study was to characterize the effects of spaceflight on oxidative damage in the mouse brain and its impact on blood-brain barrier (BBB) integrity. Ten-week-old male C57BL/6 mice were launched to the International Space Station (ISS) for 35 days as part of Space-X 12 mission. Ground control (GC) mice were maintained on Earth in flight hardware cages. Within 38 ± 4 hours after returning from the ISS, mice were euthanized and brain tissues were collected for analysis. Quantitative assessment of brain tissue demonstrated that spaceflight caused an up to 2.2-fold increase in apoptosis in the hippocampus compared to the control group. Immunohistochemical analysis of the mouse brain revealed an increased expression of aquaporin4 (AQP4) in the flight hippocampus compared to the controls. There was also a significant increase in the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) and a decrease in the expression of the BBB-related tight junction protein, Zonula occludens-1 (ZO-1). These results indicate a disturbance of BBB integrity. Quantitative proteomic analysis showed significant alterations in pathways responsible for neurovascular integrity, mitochondrial function, neuronal structure, protein/organelle transport, and metabolism in the brain after spaceflight. Changes in pathways associated with adhesion and molecular remodeling were also documented. These data indicate that long-term spaceflight may have pathological and functional consequences associated with neurovascular damage and late neurodegeneration.

Effects of Hydro-ethanolic Extract of Tanacetum parthenium and its N-Butanol and Aqueous Fractions on Brain Oxidative Damage in Pentylenetetrazole-Induced Seizures in Mice

Background: Epileptic seizures affect the life of noticeable number of people in all over the world. Tanacetum parthenium (TP) is used in traditional medicine. We studied the effects of hydro- ethanolic extract of TP and its n-butanol and aqueous fractions on brain oxidative damage in pentylenetetrazole (PTZ)-induced seizures in mice. Methods: Male mice were divided into: (1) Control; (2) PTZ (100 mg/kg, i.p.); (3-5) hydro-ethanolic extract of TP (50, 100 and 200 mg/kg); (6) n-butanol (NBut) (100 mg/kg) and (7) aqueous (Aq) (100 mg/kg) fractions. Extracts were injected (i.p.) for 3 days and 30 min before PTZ. Latencies in onset of Minimal Clonic Seizures (MCS) and Generalized Tonic-Clonic Seizures (GTCS) as well as biochemical indicators were evaluated. Results: Medium dose of TP extract and NBut fraction prolonged the MSC and GTCS latencies. Biochemical data confirmed that administration of hydro-ethanolic extract of TP significantly reduced MDA and enhanced total thiol content and the activity of SOD and CAT in brain tissues. Comparison the effect of NBut and Aq fractions with medium dose indicated a higher level of MDA and lower amount of total thiol content and the activity of SOD and CAT in brain tissues of PTZ-Aq100 and PTZ-NBut100 groups than PTZ-TP100 group. Results: demonstrated that the medium dose of TP extract had the most protective effect against brain oxidative damage in PTZ-induced seizure model. N-butanol and aqueous fractions of TP could not exert stronger effect than medium dose on reduction PTZ-induced brain oxidative stress. Results: Medium dose of TP extract and NBut fraction prolonged the MSC and GTCS latencies. Biochemical data confirmed that administration of hydro-ethanolic extract of TP significantly reduced MDA and enhanced total thiol content and the activity of SOD and CAT in brain tissues. Comparison the effect of NBut and Aq fractions with medium dose indicated a higher level of MDA and lower amount of total thiol content and the activity of SOD and CAT in brain tissues of PTZ-Aq100 and PTZ-NBut100 groups than PTZ-TP100 group. Conclusion: Results demonstrated that the medium dose of TP extract had the most protective effect against brain oxidative damage in PTZ-induced seizure model. N-butanol and aqueous fractions of TP could not exert stronger effect than medium dose on reduction PTZ-induced brain oxidative stress.

Melatonin's Impact on Antioxidative and Anti-Inflammatory Reprogramming in Homeostasis and Disease.

There is a growing consensus that the antioxidant and anti-inflammatory properties of melatonin are of great importance in preserving the body functions and homeostasis, with great impact in the peripartum period and adult life. Melatonin promotes adaptation through allostasis and stands out as an endogenous, dietary, and therapeutic molecule with important health benefits. The anti-inflammatory and antioxidant effects of melatonin are intertwined and are exerted throughout pregnancy and later during development and aging. Melatonin supplementation during pregnancy can reduce ischemia-induced oxidative damage in the fetal brain, increase offspring survival in inflammatory states, and reduce blood pressure in the adult offspring. In adulthood, disturbances in melatonin production negatively impact the progression of cardiovascular risk factors and promote cardiovascular and neurodegenerative diseases. The most studied cardiovascular effects of melatonin are linked to hypertension and myocardial ischemia/reperfusion injury, while the most promising ones are linked to regaining control of metabolic syndrome components. In addition, there might be an emerging role for melatonin as an adjuvant in treating coronavirus disease 2019 (COVID 19). The present review summarizes and comments on important data regarding the roles exerted by melatonin in homeostasis and oxidative stress and inflammation related pathologies.