Oxidative Stress In Hippocampus Research Articles

Hydroalcoholic Extract of Centella asiatica and Madecassic Acid Reverse Depressive-Like Behaviors, Inflammation and Oxidative Stress in Adult Rats Submitted to Stress in Early Life.

Major depressive disorder (MDD) is a severe disorder that causes enormous loss of quality of life, and among the factors underlying MDD is stress in maternal deprivation (MD). In addition, classic pharmacotherapy has presented severe adverse effects. Centella asiatica (C. asiatica) demonstrates a potential neuroprotective effect but has not yet been evaluated in MD models. This study aimed to evaluate the effect of C. asiatica extract and the active compound madecassic acid on possible depressive-like behavior, inflammation, and oxidative stress in the hippocampus and serum of young rats submitted to MD in the first days of life. Rats (after the first day of birth) were separated from the mother for 3h a day for 10days. When adults, these animals were divided into groups and submitted to treatment for 14days. After subjecting the animals to protocols of locomotor activity in the open field and behavioral despair in the forced swimming test, researchers then euthanized the animals. The hippocampus and serum were collected and analyzed for the inflammatory cytokines and oxidative markers. The C. asiatica extract and active compound reversed or reduced depressive-like behaviors, inflammation in the hippocampus, and oxidative stress in serum and hippocampus. These results suggest that C. asiatica and madecassic acid have potential antidepressant action, at least partially, through anti-inflammatory and antioxidant profiles.

Subchronic Exposure to Mixture of Cadmium, Copper, and Nickel Induces Neurobehavioral Deficits and Hippocampal Oxidative Stress of Wistar Rats.

The present study was aimed at evaluating the influence of the subchronic exposure of cadmium (Cd), copper (Cu), and nickel (Ni) mixtures on affective behaviors, memory impairment, and oxidative stress (OS) in the hippocampus. Thirty male Wistar rats were divided into 5 equal groups. Group 1 (control) received a saline solution (NaCl 0.9%). Groups 2, 3, and 4 received Cd (0.25 mg/kg), Cu (0.5 mg/kg), and Ni (0.25 mg/kg), respectively, while group 5 received a Cd, Cu, and Ni mixture through intraperitoneal injections for 2 months. After the exposure period, all rats were submitted to behavioral tests. Subsequently, OS markers and histological changes in the rats' hippocampi were assessed. Results showed that a 2-month exposure to the mixtures of metals (MM) has led to higher anxiety-like and depression-like behaviors and cognitive deficits in rats when compared to the control group and the individual metals. Furthermore, the MM induced heightened OS, evidenced by the rise in lipid peroxidation and nitric oxide levels. These effects were accompanied by a decrease in superoxide dismutase and catalase activities in the hippocampus. The histopathological analysis also supported that MM caused a neuronal loss in the CA3 sub-region. Overall, this study underscores that subchronic exposure to the Cd, Cu, and Ni mixture induces an OS status and histological changes in the hippocampus, with important affective and cognitive behavior variations in rats.

Edaravone dexborneol attenuates cognitive impairment in a rat model of vascular dementia by inhibiting hippocampal oxidative stress and inflammatory responses and modulating the NMDA receptor signaling pathway

Exploring the intricate pathogenesis of Vascular Dementia (VD), there is a noted absence of potent treatments available in the current medical landscape. A new brain-protective medication developed in China, Edaravone dexboeol (EDB), has shown promise due to its antioxidant and anti-inflammatory properties, albeit with a need for additional research to elucidate its role and mechanisms in VD contexts. In a research setup, a VD model was established utilizing Sprague-Dawley (SD) rats, subjected to permanent bilateral typical carotid artery occlusion (2VO). Behavioral assessment of the rats was conducted using the Bederson test and pole climbing test, while cognitive abilities, particularly learning and memory, were evaluated via the novel object recognition test and the Morris water maze test. Ensuing, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), IL-1β, IL-6, IL-4, and tumor necrosis factor-α (TNF-α) were determined through Enzyme-Linked Immunosorbent Assay (ELISA). Synaptic plasticity-related proteins, synaptophysin (SYP), post-synaptic density protein 95 (PSD-95), and N-methyl-D-aspartate (NMDA) receptor proteins (NR1, NR2A, NR2B) were investigated via Western blotting technique. The findings imply that EDB has the potential to ameliorate cognitive deficiencies, attributed to VD, by mitigating oxidative stress, dampening inflammatory responses, and modulating the NMDA receptor signaling pathway, furnishing new perspectives into EDB’s mechanism and proposing potential avenues for therapeutic strategies in managing VD.

CoQ10 targeted hippocampal ferroptosis in a status epilepticus rat model.

Status epilepticus (SE), the most severe form of epilepsy, leads to brain damage. Uncertainty persists about the mechanisms that lead to the pathophysiology of epilepsy and the death of neurons. Overloading of intracellular iron ions has recently been identified as the cause of a newly recognized form of controlled cell death called ferroptosis. Inhibiting ferroptosis has shown promise as a treatment for epilepsy, according to recent studies. So, the current study aimed to assess the possible antiepileptic impact of CoQ10 either alone or with the standard antiepileptic drug sodium valproate (SVP) and to evaluate the targeted effect of COQ10 on hippocampal oxidative stress and ferroptosis in a SE rat model. Using a lithium-pilocarpine rat model of epilepsy, we evaluated the effect of SVP, CoQ10, or both on seizure severity, histological, and immunohistochemical of the hippocampus. Furthermore, due to the essential role of oxidative stress and lipid peroxidation in inducing ferroptosis, we evaluated malonaldehyde (MDA), reduced glutathione (GSH), glutathione peroxidase 4 (GPX4), and ferritin in tissue homogenate.Our work illustrated that ferroptosis occurs in murine models of lithium-pilocarpine-induced seizures (epileptic group). Nissl staining revealed significant neurodegeneration. A significant increase in the number of astrocytes stained with an astrocyte-specific marker was observed in the hippocampus. Effective seizure relief can be achieved in the seizure model by administering CoQ10 alone compared to SVP. This was accomplished by lowering ferritin levels and increasing GPX4, reducing MDA, and increasing GSH in the hippocampus tissue homogenate. In addition, the benefits of SVP therapy for regulating iron stores, GPX4, and oxidative stress markers were amplified by incorporating CoQ10 as compared to SVP alone. It was concluded that CoQ10 alone has a more beneficial effect than SVP alone in restoring histological structures and has a targeted effect on hippocampal oxidative stress and ferroptosis. In addition, COQ10 could be useful as an adjuvant to SVP in protecting against oxidative damage and ferroptosis-related damage that result from epileptic seizures.

The relationship between thiamin, folic acid and cognitive function in a rat model of uremia

End-stage renal disease is a worldwide health burden, but the pathogenesis of uremia-associated cognitive impairment (CI) is poorly recognized. We hypothesized that uremia brings about deficiency of thiamin and folic acid and causes CI by inducing oxidative stress. Therefore, 24 Sprague-Dawley rats were randomly divided into two groups: a 5/6 nephrectomy group (n = 12) and a sham-operated group (n = 12). The Morris water maze was used to assess the cognitive function eight weeks post-surgery, and serum levels of thiamin, folic acid and homocysteine were detected subsequently. Brain and kidney tissues were collected for pathological examination and 8-Hydroxy-2’-deoxyguanosine (8-OHdG) immunochemistry staining. Results showed that the escape latency on training days 1-2 was longer, and the time in quadrant IV on experimental day 6 was significantly shorter in 5/6 nephrectomy group. Meanwhile, the uremic rats showed decreased thiamin, folic acid and increased homocysteine. We also found the time in quadrant IV was positively correlated with thiamin and folic acid level, while negatively correlated with the blood urea nitrogen and 8-OHdG positive cell proportion. Furthermore, in 5/6 nephrectomy group, the hippocampal neuron count was significantly reduced, and a greater proportion of 8-OHdG positive cells were detected. Pretreating LPS-stimulated rat microglial cells with thiamin or folic acid in vitro alleviated the inflammatory impairment in terms of cell viability and oxidative stress. In summary, we applied a uremic rat model and proved that uremia causes serum thiamin and folic acid deficiency, homocysteine elevation, along with neuron reduction and severe oxidative stress in hippocampus, finally leading to CI.

Chronic exposure to PM10 induces anxiety-like behavior via exacerbating hippocampal oxidative stress

As one of the most environmental concerns, inhaled particulate matter (PM10) causes numerous health problems. However, the associations between anxiety behavior and toxicity caused by PM10 have rarely been reported so far. To investigate the changes of behavior after PM10 exposure and to identify the potential mechanisms of toxicity, PM10 samples (with doses of 15 mg/kg and 30 mg/kg) were intratracheally instilled into rats to simulate inhalation of polluted air by the lungs. After instillation for eight weeks, anxiety-like behavior was evaluated, levels of oxidative stress and morphological changes of hippocampus were measured. The behavioral results indicated that PM10 exposure induced obvious anxiety-like behavior in the open field and elevated plus maze tests. Both PM10 concentrations tested could increase whole blood viscosity and trigger hippocampal neuronal damage and oxidative stress by increasing superoxide dismutase (SOD) activities and malondialdehyde levels, and decreasing the expressions of antioxidant-related proteins (e.g., nuclear factor erythroid 2-related factor 2 (Nrf2), SOD1 and heme oxygenase 1). Furthermore, through collecting and analyzing questionnaires, the data showed that the participants experienced obvious anxiety-related emotions and negative somatic responses under heavily polluted environments, especially PM10 being the main pollutant. These results show that PM10 exposure induces anxiety-like behavior, which may be related to suppressing the Nrf2/Keap1-SOD1 pathway.

Oral administration of ellagic acid mitigates perioperative neurocognitive disorders, hippocampal oxidative stress, and neuroinflammation in aged mice by restoring IGF-1 signaling

This study investigates the potential of ellagic acid (EA), a phytochemical with antioxidant and anti-inflammatory properties, in managing perioperative neurocognitive disorders (PND). PND, which represents a spectrum of cognitive impairments often faced by elderly patients, is principally linked to surgical and anesthesia procedures, and heavily impacted by oxidative stress in the hippocampus and microglia-induced neuroinflammation. Employing an aged mice model subjected to abdominal surgery, we delve into EA's ability to counteract postoperative oxidative stress and cerebral inflammation by engaging the Insulin-like growth factor-1 (IGF-1) pathway. Our findings revealed that administering EA orally notably alleviated post-surgical cognitive decline in older mice, a fact that was manifested in improved performance during maze tests. This enhancement in the behavioral performance of the EA-treated mice corresponded with the rejuvenation of IGF-1 signaling, a decrease in oxidative stress markers in the hippocampus (like MDA and carbonylated protein), and an increase in the activity of antioxidant enzymes such as SOD and CAT. Alongside these, we observed a decrease in microglia-driven neuroinflammation in the hippocampus, thus underscoring the antioxidant and anti-inflammatory roles of EA. Interestingly, when EA was given in conjunction with an IGF1R inhibitor, these benefits were annulled, accentuating the pivotal role that the IGF-1 pathway plays in the neuroprotective potential of EA. Hence, EA could serve as a potent candidate for safeguarding against PND in older patients by curbing oxidative stress and neuroinflammation through the activation of the IGF-1 pathway.

Insights into early pathogenesis of sporadic Alzheimer's disease: role of oxidative stress and loss of synaptic proteins.

Oxidative stress, induced by impaired insulin signaling in the brain contributes to cognitive loss in sporadic Alzheimer's disease (sAD). This study evaluated early hippocampal oxidative stress, pre- and post-synaptic proteins in intraperitoneal (IP) and intracerebroventricular (ICV) streptozotocin (STZ) models of impaired insulin signaling. Adult male Wistar rats were injected with STZ, IP, or ICV, and sacrificed 1-, 3-, or 6-weeks post injection. Rat's cognitive behavior was assessed using Morris water maze (MWM) tests at weeks 3 and 6. Hippocampal synaptosomal fractions were examined for oxidative stress markers and presynaptic [synapsin I, synaptophysin, growth-associated protein-43 (GAP-43), synaptosomal-associated protein-25 (SNAP-25)] and postsynaptic [drebrin, synapse-associated protein-97 (SAP-97), postsynaptic density protein-95 (PSD-95)] proteins. IP-STZ and ICV-STZ treatment impaired rat's cognition, decreased the levels of reduced glutathione (GSH) and increased the levels of thiobarbituric acid reactive species (TBARS) in a time dependent manner. In addition, it reduced the expression of pre- and post-synaptic proteins in the hippocampus. The decline in cognition is significantly correlated with the reduction in synaptic proteins in the hippocampus. In conclusion, impaired insulin signaling in the brain is deleterious in causing early synaptosomal oxidative damage and synaptic loss that exacerbates with time and correlates with cognitive impairments. Our data implicates oxidative stress and synaptic protein loss as an early feature of sAD and provides insights into early biochemical and behavioral changes during disease progression.

Chronic stress-induced anxiety-like behavior, hippocampal oxidative, and endoplasmic reticulum stress are reversed by young plasma transfusion in aged adult rats.

Aging and stress synergistically induce behavioral dysfunctions associated with oxidative and endoplasmic reticulum (ER) stress in brain regions. Considering the rejuvenating effects of young plasma on aging brain function, in the current study, we examined the effects of young plasma administration on anxiety-like behavior, NADH oxidase, NADPH oxidase, and ER stress markers in the hippocampus of old male rats. Young (3 months old) and aged (22 months old) rats were randomly assigned into five groups: young control (Y), aged control (A), aged rats subjected to chronic stress for four weeks (A+S), aged rats subjected to chronic stress and treated with old plasma (A+S+OP), and aged rats subjected to chronic stress and treated with young plasma (A+S+YP). Systemic injection of (1 ml) young and old plasma was performed for four weeks (3 times/week). Young plasma transfusion significantly improved anxiety-like behavior in aged rats and modulated oxidative stress in the hippocampus, evidenced by the increased NADH oxidase (NOX) activity and the reduced NADPH oxidase. In addition, the levels of C/EBP homologous protein (CHOP) and Glucose-Regulated Protein 78 (GRP-78), as ER stress markers, markedly reduced in the hippocampus following the administration of young plasma. These findings suggest that young plasma transfusion could reverse anxiety-like behavior in stress-exposed aged rats by modulating the hippocampal oxidative and ER stress markers.

Rice bran extract mitigates depressive-like behavior in dextran sulfate sodium-induced colitis: Involvement of the gut-brain axis and Sirt1 signaling pathway

Inflammatory bowel disease (IBD) patients frequently suffer from depressive disorders as well. The present study was carried out to explore whether treatment with a standardized rice bran extract (RBE) could affect depression-like behavior in rats with dextran sulfate sodium (DSS)-induced colitis. Male Wistar rats were treated with RBE (100 mg/kg/day; p.o.) for 2 weeks. During the second week, colitis was induced by feeding the rats with 5 % (w/v) DSS in drinking water. RBE protected against DSS-induced body weight loss as well as against the macro- and microscopic inflammatory changes of the colon. Additionally, RBE mitigated DSS-induced dysregulation in blood–brain barrier tight junctional proteins, preserved the hippocampal histopathological architecture and improved the animal behavior in the forced swimming test. This was associated with modulation of hippocampal oxidative stress marker; GSH as well as hippocampal pro-inflammatory mediators; NF-ĸB and IL-1β. Treatment with RBE also led to a profound increase in the hippocampal levels of Sirt1, PGC-1α, Nrf2, and HO-1, which were drastically dropped by DSS. In conclusion, the study revealed the protective effect of RBE against DSS-induced depressive-like behavior through modulation of different parameters along the gut-brain axis and up-regulated the Sirt1/PGC-1α/Nrf2/HO-1 signaling pathway.

NEUROPROTECTIVE EFFECT OF PERILLYL ALCOHOL IN EXPERIMENTAL SPORADIC AD

AbstractBackgroundAlzheimer’s is most common neurodegenerative disorder characterized by memory loss due to accumulation of amyloid‐ β fibrils. There are different pathologies that count for AD like neuro inflammation. This study highlights the role of oxidative stress and inflammation in progression of AD where as Perillyl alcohol (POH) shows antioxidative & anti‐inflammatory properties.MethodSprague Dawley ICV‐STZ (3mg/kg) rats (250‐300g, 7‐8 weeks) were treated with Perillyl alcohol treated with three different doses of (25, 50 and 100mg/kg p.o.) for 13 days from 15th to 27th day. Weight measured on 1st and 28th day. Behavioral analysis done using Open Field Test and Morris Water Maze.ResultPerillyl alcohol treatment significantly attenuates declined body weight in ICV‐STZ induced dementia in rats, showed significant increase in crossing number, and active time. Dementia induced rats were unable to discriminate familiar and novel objects, which is improved by POH. POH attenuates STZ induced acquisition deficits and retention time, increased MDA and nitrite levels. POH attenuated depleted levels of GSH, Catalase, SOD comparable to standard drug donepezil, POH decreased AChE levels in cortex and hippocampus.ConclusionStudy outcomes demonstrate neuroprotective potential of Perillyl alcohol against ICV‐STZ administration of streptozotocin induced behavioural and biochemical abnormalities. Biventricular STZ infusion produced significant impairment in learning, memory, cholinergic hypofunction and elevation in hippocampal oxidative stress in rats. Rats showed poor learning, memory and unable to discriminate between familiar & novel objects in MWM and ORT. POH administration significantly attenuated STZ induced biochemical consequences. Observed beneficial effects of POH include restored cholinergic functions and antioxidant mechanism

Disruption of Cdk5-GluN2B complex by a small interfering peptide attenuates social isolation-induced escalated intermale attack behavior and hippocampal oxidative stress in mice

Social isolation has emerged as a significant issue during the COVID-19 pandemic that can adversely impact human mental health and potentially lead to pathological aggression. Given the lack of effective therapeutic interventions for aggressive behavior, alternative approaches are necessary. In this study, we utilized a genetic method combined with a pharmacological approach to identify and demonstrate the crucial role of Cdk5 in escalated intermale attack behavior induced by 2-week social isolation. Moreover, we developed a small peptide that effectively disrupts the interaction between Cdk5 and GluN2B, given the known involvement of this complex in various neuropsychiatric disorders. Administration of the peptide, either systemically or via intrahippocampal injection, significantly reduced oxidative stress in the hippocampus and attenuated intermale attack behavior induced by 2-week social isolation. These findings highlight the previously unknown role of the hippocampal Cdk5-GluN2B complex in social isolation-induced aggressive behavior in mice and propose the peptide as a promising therapeutic strategy for regulating attack behavior and oxidative stress.

Effect of vitamin E on doxorubicin and paclitaxel-induced memory impairments in male rats.

In addition to peripheral neuronal dysfunction, conventional chemotherapy can be associated with other neurological treatment-limiting adverse effects, including cognitive dysfunction, memory impairment, and anxiety, which are referred to as "chemobrain". This study aimed to investigate the effects of doxorubicin (DOX) and paclitaxel (PAC) on learning and memory in rats using radial arm water maze (RAWM) and investigated a potential beneficial effect of vitamin E(Vit. E). Adult male rats were injected with four doses of 2mg/kg/week DOX, or 2mg/kg PAC every other day intraperitoneally. Vit. Ewas co-administered with these drugs in other groups to study its antioxidative effects. Using the RAWM, each rat was assessed for learning and memory performance through two sets of six trials separated by a 5-min rest period evaluating both short- and long-term effects on memory. There was no deficit in learning or long-term memory in both drug groups compared to control. However, rats in both drug groups made significantly more errors in all short-term memory trials. This effect was mitigated when Vit. E was co-administered with either drug. Moreover, PAC (but not DOX) induced hippocampal lipid peroxidation by increasing the levels of standard biomarker thiobarbituric acid reactive substances(TBARS). Interestingly, Vit. E prevented PAC-induced hippocampal oxidative stress. Furthermore, both DOX and PAC were correlated with reduction in Brain-Derived Neurotrophic Factor (BDNF) expression levelsin the hippocampus, which was overcome by the co-administration of Vit. E. There is a potential role of Vit. E in alleviating short-term memory impairment in rats exposed to chemotherapy, possibly by reducing hippocampal oxidative stress and neurodegeneration.

Protective effects of alpha-lipoic acid on anxiety-like behavior, memory and prevention of hippocampal oxidative stress in methamphetamine-treated rats.

Alpha-lipoic acid is an essential cofactor for aerobic metabolism and acts as a potent antioxidant in the body. It has been shown that acute exposure to methamphetamine induces oxidative stress, which is responsible for severe cognitive deficits in animals. The hippocampus plays a crucial role in the processing of memory and anxiety-like behavior. In this study, preventive effect of the alpha-lipoic acid on memory impairment in methamphetamine-induced neurotoxicity was investigated. Wistar male rats (200-220g) were allocated to five groups (seven rats in each group): (1) saline + saline, (2) saline + vehicle (sunflower oil as alpha-lipoic acid solvent), (3) methamphetamine + vehicle, (4) methamphetamine + alpha-lipoic acid 10mg/kg, and (5) methamphetamine + alpha-lipoic acid 40mg/kg. Rats received intraperitoneal methamphetamine repeatedly (2 × 20mg/kg, 2h interval). Alpha-lipoic acid was injected 30min, 24h, and 48h after the last injection of methamphetamine. The passive avoidance test and open field were used for evaluation of memory retrieval and anxiety, respectively. After behavioral test, rats were anesthetized, their brains were extracted, and after preparing hippocampal homogenates, malondialdehyde (MDA) level, catalase, and superoxide dismutase (SOD) activities were evaluated. Statistical analysis showed that injection of saline or sunflower oil had no significant effect on anxiety, memory, or oxidative stress markers. Methamphetamine induced memory impairment, increased anxiety-like behavior and MDA level, but it reduced catalase and SOD activity. Treatment with alpha-lipoic acid decreased MDA, increased catalase and SOD activity, and also prevented memory impairment and anxiety-like behavior. Our results showed that alpha-lipoic acid protected the hippocampus from oxidative stress by elevating SOD and CAT activities and reduced memory impairment following acute methamphetamine injection. These findings suggest that alpha-lipoic acid may have a protective effect against the adverse effects of methamphetamine exposure on the hippocampus. Therefore, the current data indicated that ALA can reduce oxidative stress predominantly by its antioxidant property.

Evaluating the protective role of trimetazidine versus nano-trimetazidine in amelioration of bilateral renal ischemia/reperfusion induced neuro-degeneration: Implications of ERK1/2, JNK and Galectin-3 /NF-κB/TNF-α/HMGB-1 signaling

BackgroundRenal ischemia/reperfusion (I/R) is a primary culprit of acute kidney injury. Neurodegeneration can result from I/R, but the mechanisms are still challenging. We studied the implications of bilateral renal I/R on brain and potential involvement of the oxidative stress (OS) driven extracellular signal-regulated kinase1/2, c-Jun N-terminal kinase (ERK1/2, JNK) and Galectin-3 (Gal-3)/nuclear factor Kappa B (NF-қB)/tumor necrosis factor-alpha (TNF-α), high mobility group box-1 (HMGB-1), and caspase-3 paths upregulation. We tested the impact of Nano-trimetazidine (Nano-TMZ) on these pathways being a target of its neuroprotective effects. MethodsStudy groups; Sham, I/R, TMZ+I/R, and Nano-TMZ+I/R. Kidney functions, cognition, hippocampal OS markers, Gal-3, NF-қB, p65 and HMGB-1 gene expression, TNF-α level, t-JNK/p-JNK and t-ERK/p-ERK proteins, caspase-3, glial fibrillary acidic protein (GFAP) and ionized calcium binding protein-1 (Iba-1) were assessed. ResultsNano-TMZ averted renal I/R-induced hippocampal impairment by virtue of its anti: oxidative, inflammatory, and apoptotic properties. ConclusionNano-TMZ is more than anti-ischemic.

Nilotinib treatment induces cognitive impairment by elevating hippocampal oxidative stress in rats.

Protein tyrosine kinases (TKs) play a critical role in the regulation of various functions of a cell, including cellular proliferation, differentiation, and growth, and inhibitors of TKs have emerged as next-generation therapeutic agents in various types of cancer. Nilotinib, one of the TK inhibitors used to treat chronic myeloid leukemia, has been poorly investigated for its potential impact on memory function despite its ability to cross the blood-brain barrier (BBB). Thus, in this study, we investigated the effect of nilotinib on hippocampal-dependent cognitive functions and its potential mechanisms. Wistar albino male rats were divided into three groups of 10 each. The animals of group I (normal control) received drinking water only, while groups II and III were treated with nilotinib at doses of 15 mg/kg and 30 mg/kg, p.o. respectively, once daily for two weeks. The animals were subjected to behavioral tests after completion of drug treatment for the assessment of cognitive function using the Y-maze, novel object recognition (NOR) test, and elevated plus maze (EPM). The animals were euthanized after the estimation of blood glucose, and hippocampal tissues were dissected for the estimation of markers of oxidative stress. Nilotinib produced impairment of memory function on the Y-maze, NOR test, and EPM. These results were also supported by a significant increase in glutathione (GSH), malondialdehyde (MDA), Akt, glycogen synthase kinase-3 beta (GSK3β), and total antioxidant capacity (TAC) in hippocampal tissue without altering the blood glucose level. Nilotinib treatment produced significant impairment of cognitive function by inducing oxidative stress in the hippocampal tissue of rats.

Sevoflurane-induced hypotension causes cognitive dysfunction and hippocampal inflammation in mice

Sevoflurane commonly adopted for anesthetic in clinical practice, however, its influences on cerebral blood flow and cognitive function remain controversial. Herein, the sevoflurane-induced hypotension on arterial blood pressure, cerebral blood flow, cognitive function, and hippocampal inflammation was investigated in mice. A significant decrease in arterial blood pressure and cerebral blood flow was indicated by the sevoflurane anesthesia treatment. Moreover, sevoflurane-induced hypotension was associated with the impaired cognitive function and the increased levels of NLRP3 inflammasome activation and oxidative stress in hippocampus. These findings suggest that sevoflurane-induced hypotension may lead to the cognitive dysfunction and hippocampal inflammation.

Prangos ferulacea (L.) ameliorates behavioral alterations, hippocampal oxidative stress markers, and apoptotic deficits in a rat model of autism induced by valproic acid.

Prenatal exposure to valproic acid (VPA) may enhance the risk of autism spectrum disorder (ASD) in children. This study investigated the effect of Prangos ferulacea (L.) on behavioral alterations, hippocampal oxidative stress markers, and apoptotic deficits in a rat model of autism induced by valproic acid. Pregnant rats received VPA (600mg/kg, intraperitoneally [i.p.]) or saline on gestational day 12.5 (E 12.5). Starting from the 30th postnatal day (PND 30), the pups were i.p. administered Prangos ferulacea (PF, 100 and 200mg/kg), or the vehicle, daily until PND 58. On PND 30 and 58, various behavioral tasks were used to evaluate pups, including the open field, elevated plus-maze, hot-plate, and rotarod test. On PND 65, the animals were euthanized, and their brains were removed for histopathological and biochemical assay. Prenatal exposure to VPA caused significant behavioral changes in the offspring, reversed by administering an extract of Prangos ferulacea (L.). Additionally, prenatal VPA administration resulted in increased levels of malondialdehyde and deficits in antioxidant enzyme activities in the hippocampus, including catalase and glutathione, ameliorated by PF. Likewise, postnatal treatment with PF improved VPA-induced dysregulation of Bax and Blc2 in the hippocampus and reduced neuronal death in CA1, CA3, and dentate gyrus. The findings of this study suggest that postnatal administration of PF can prevent VPA-induced ASD-like behaviors by exhibiting antiapoptotic and antioxidant properties. Therefore, PF may have the potential as an adjunct in the management of ASD.

Ginsenoside Re blocks Bay k-8644-induced neurotoxicity via attenuating mitochondrial dysfunction and PKCδ activation in the hippocampus of mice: Involvement of antioxidant potential.

Although the anticonvulsant effects of ginsenosides are recognized, little is known about their effects on the convulsive behaviors induced by the activation of L-type Ca2+ channels. Here, we investigated whether ginsenoside Re (GRe) modulates excitotoxicity induced by the L-type Ca2+ channel activator Bay k-8644. GRe significantly attenuated Bay k-8644-induced convulsive behaviors and hippocampal oxidative stress in mice. GRe-mediated antioxidant potential was more pronounced in the mitochondrial fraction than cytosolic fraction. As L-type Ca2+ channels are thought to be targets of protein kinase C (PKC), we investigated the role of PKC under excitotoxic conditions. GRe attenuated Bay k-8644-induced mitochondrial dysfunction, PKCδ activation, and neuronal loss. The PKCδ inhibition and neuroprotection mediated by GRe were comparable to those by the ROS inhibitor N-acetylcysteine, the mitochondrial protectant cyclosporin A, the microglial inhibitor minocycline, or the PKCδ inhibitor rottlerin. Consistently, the GRe-mediated PKCδ inhibition and neuroprotection were counteracted by the mitochondrial toxin 3-nitropropionic acid or the PKC activator bryostatin-1. GRe treatment did not have additional effects on PKCδ gene knockout-mediated neuroprotection, suggesting that PKCδ is a molecular target of GRe. Collectively, our results suggest that GRe-mediated anticonvulsive/neuroprotective effects require the attenuation of mitochondrial dysfunction and altered redox status and inactivation of PKCδ.

Neuroprotective Effect of Perillyl alcohol in Experimental Sporadic Alzheimer’s disease

AbstractBackgroundAlzheimer’s is most common neurodegenerative disorder characterized by memory loss due to accumulation of amyloid‐ β fibrils. There are different pathologies that count for AD like neuro‐inflammation. This study highlights the role of oxidative stress and inflammation in progression of AD whereas Perillyl alcohol (POH) shows ant oxidative & anti‐inflammatory properties.Method54 Sprague Dawley ICV‐STZ (3mg/kg) rats (250‐300g, 7‐8 weeks) were treated with three different doses of Perillyl alcohol (25, 50 and 100mg/kg p.o.) for 13 days from 15th to 27th day. Weight measured on 1st and 28th day. Behavioral analysis had done using OFT and MWM.ResultPerillyl alcohol treatment significantly attenuates declined body weight in ICV‐STZ induced dementia in rats, showed significant increase in crossing number, and active time. Dementia induced rats were unable to discriminate familiar and novel objects, which is improved by POH. POH attenuates STZ induced acquisition deficits and retention time, increased MDA and nitrite levels. POH attenuated depleted levels of GSH, Catalase, SOD comparable to standard drug donepezil, POH decreased AChE levels in cortex and hippocampus.ConclusionStudy outcomes demonstrate neuroprotective potential of Perillyl alcohol against ICV‐STZ administration of streptozotocin induced behavioural and biochemical abnormalities. Biventricular STZ infusion produced significant impairment in learning, memory, cholinergic hypo function and elevation in hippocampal oxidative stress in rats. Rats showed poor learning, memory and unable to discriminate between familiar & novel objects in MWM and ORT. POH administration significantly attenuated STZ induced biochemical consequences. Observed beneficial effects of POH include restored cholinergic functions and antioxidant mechanisms.