Brain Histopathology Research Articles

Selenium nanoparticles impart robust neuroprotection against deltamethrin-induced neurotoxicity in male rats by reversing behavioral alterations, oxidative damage, apoptosis, and neuronal loss

This study investigated the neuroprotective role of selenium nanoparticles (SeNPs) on deltamethrin-induced neurotoxicity in rats. A total of 32 adult male Wister rats were allocated into the following four groups: 1) control, 2) deltamethrin (0.6 mg/kg), 3) SeNPs (0.5 mg/kg), and 4) deltamethrin + SeNPs. All agents were administered orally three times per week for 2 months. Locomotor behavior, anxiety-like behavior, biochemical parameters, including brain oxidative damage biomarkers (Malondialdehyde (MDA) and reduced glutathione (GSH)), brain acetylcholinesterase (AChE), and brain genotoxicity were evaluated. The gene expression levels of IGF-1 and Bcl2 were also determined. Moreover, a brain histopathological examination associated with the immunohistochemical determination of Bax in brain tissue was performed. Deltamethrin-intoxicated rats showed a reduction in the locomotor activity associated with a highly anxious state. They also displayed a disturbance in the brain redox state with a decrease in the brain AChE levels and a high DNA fragmentation percentage. Furthermore, they showed a decrement in the immunohistochemical GFAP levels as well as IGF-1 and Bcl2 gene expression levels with an increase in the immunohistochemical Bax levels. All these changes were confirmed by brain histopathology. Interestingly, SeNPs ameliorated all these changes and restored the normal brain architecture. In conclusion. SeNPs possess a potent medicinal activity due to their antioxidant and anti-inflammatory activity. Therefore, SeNPs can be a potential agent in ameliorating deltamethrin-induced neurotoxicity.

Punicalagin Alleviates Oxidative Stress and Pathological Changes in Brain of Mice-Fed High Fat, High Fructose Diet

The present study investigated to know whether the pomegranate polyphenol punicalagin (PU) can ameliorate oxidative stress and pathological alterations induced by a calorie rich diet comprised of fat and fructose. Male Swiss albino mice were fed normal pellet (Control) or high fat-high fructose diet (HFFD) for 60 days. PU (30 or 60 mg/kg bw) was administered orally for the last 15 days for both dietary groups. Measurement of TBARS, AOPP and FRAP in plasma, histopathology of liver and brain, assessment of oxidative damage in brain tissues, and blood brain barrier function were carried out. HFFD mice showed an increase in the levels of TBARS and AOPP, and a decline in FRAP. PU administration to HFFD mice reduced the levels of TBARS and AOPP and improved FRAP significantly. Histopathology results showed fatty changes and inflammatory infiltration in the liver of HFFD mice. Cortex and hippocampus of HFFD mice confirmed the presence of degenerating neurons with shrunken cytoplasm and pyknotic nuclei. PU treatment caused significant hepato and neuroprotective effects, and among the two doses the high dose of PU (60 mg/kg) showed more pronounced effects than the low dose (30 mg/kg). The immunohistochemical localization of the markers of oxidative damage to proteins (3-NT), lipids (4-HNE) and DNA (8-OHG) was increased in brain tissues of HFFD mice and upon PU administration (60 mg/kg) the levels of these oxidative stress markers were significantly decreased. Our findings clearly suggest that PU can modulate oxidative stress and could be a potential candidate for treating neurodegenerative processes associated with calorie excess.

MicroRNA-489-3p aggravates neuronal apoptosis and oxidative stress after cerebral ischemia-reperfusion injury

ABSTRACT Cerebral ischemia-reperfusion injury (CIRI) mostly occurs in the treatment stage of ischemic diseases and aggravate brain tissue damage. Although studies have demonstrated that miR-489-3p is closely related to CIRI, the effects of miR-489-3p on neural function in CIRI have not been directly studied. The transient middle cerebral artery occlusion (tMCAO) model was established by suture method, and the corresponding plasmids that interfered with the expression of miR-489-3p or Sirtuin1 (SIRT1) were injected into the model mice, and the behavioral changes of the mice were observed. Then the concentration of serum neuronal injury markers and oxidative stress indices were examined. Next, the pathological conditions, neuronal loss and apoptosis of brain tissue were observed by hematoxylin-eosin staining, Nissl staining, and Transferase-mediated deoxyuridine triphosphate-biotin nick end labeling staining. Finally, the hemoglobin content and cerebral edema in the mouse brain were determined. In addition, the expression levels of miR-489-3p and SIRT1 were detected by reverse transcription quantitative polymerase chain reaction or Western blot, and the targeting relationship between miR-489-3p and SIRT1 was verified by bioinformatics analysis and luciferase reporter assay. The experimental results found that in tMCAO mice, miR-489-3p in brain tissue was up-regulated and SIRT1 was down-regulated. Down-regulating miR-489-3p or up-regulating SIRT1 ameliorated behavioral dysfunction, neuronal damage and apoptosis, oxidative stress and brain histopathology. miR-489-3p targeted the regulation of SIRT1 expression, and down-regulating SIRT1 can reverse the protective effect of silenced miR-489-3p on brain injury. Taken together, by targeting SIRT1, elevated miR-489-3p aggravates CIRI-induced neuronal apoptosis and oxidative stress.

Chuanzhi Tongluo Capsules antagonizes cerebral ischemia-reperfusion injury in mice by inhibiting neuroinflammation and oxidative stress

Chuanzhi Tongluo Capsules(CZTL) is effective in activating blood, resolving stasis, replenishing Qi, and dredging collaterals, which has been widely used in clinical treatment of stroke(cerebral infarction) differentiated into the syndrome of wind striking meridian and collateral in the recovery stage characterized by blood stasis and Qi deficiency. However, its modern pharmacological mechanisms of action remain unclear. This study duplicated the middle cerebral artery occlusion and reperfusion(MCAO/R) model in mice using the suture-occluded method to explore the protective effect and mechanism of CZTL on ischemic stroke. The mice were divided into the sham-operation group, model group, and CZTL group. The ones in the CZTL group were gavaged with 0.3 g·kg~(-1)·d~(-1) CZTL for three successive days. One hour after the last intragastric administration, those in the model and CZTL groups were subjected to MCAO/R. After 24 h reperfusion, the effects of CZTL on neurological deficit score, cerebral infarction area, brain edema, and brain histopathology were evaluated. The levels of reactive oxygen species(ROS), malondialdehyde(MDA), interleukin-6(IL-6), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α) and the activity of superoxide dismutase(SOD) in brain tissue homogenate were detected using corresponding assay kits. The expression of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), Toll like receptor 4(TLR4), and phosphorylated nuclear factor-κB P65 subunit(p-NF-κB P65) were assayed by Western blot. The results indicated that CZTL significantly reduced the neurological deficit score, brain edema, and infarct volume, improved the brain histopathology, inhibited the expression of ROS, MDA, IL-6, IL-1β, and TNF-α in the brain tissue, and up-regulated the activity of SOD, down-regulated the expression of pro-apoptotic protein Bax, promoted the expression of anti-apoptotic protein Bcl-2, and suppressed the expression of TLR4 and p-NF-κB P65 phosphorylation of MCAO/R mice. All these have demonstrated that CZTL has a significant protective effect against MCAO/R injury in mice, which may be related to its resistance to neuroinflammation and oxidative stress.

The clinical spectrum of haemorrhagic CNS inflammatory demyelinating lesions

Background: Haemorrhagic demyelinating lesions are rare, and little is known about the demyelinating diseases with which they are associated, or how lesional haemorrhage affects treatment and outcomes. Objective: To examine the clinical characteristics and outcomes of patients with demyelinating lesions and magnetic resonance imaging (MRI) evidence of haemorrhage seen at the Mayo clinic between 1990 and 2018. Methods: The Mayo Clinic’s medical-record diagnostic-linkage system was used to identify patients with CNS demyelinating disease and parenchymal haemorrhage on brain MRI cross-referenced against a database of patients with pathologically confirmed CNS demyelinating disease. The clinical characteristics, diagnosis, MRI findings, brain histopathology, and outcomes of these patients were reviewed. Results: Ten patients with haemorrhagic demyelination were identified, including three patients who underwent a brain biopsy. The main findings were that haemorrhagic demyelinating lesions most often occur in atypical forms of demyelination, especially acute haemorrhagic leukoencephalitis (AHL, or Weston–Hurst disease) and tumefactive demyelination, and rarely in multiple sclerosis. A spectrum of outcomes was observed for these patients ranging from complete remission through to high level disability. Conclusion: Lesional haemorrhage is uncommon in demyelinating disease where it is most closely associated with AHL. Bleeding within a demyelinating lesion does not always herald a poor prognosis.

Preventing neonatal herpes: Protection after maternal mRNA-lipid nanoparticle vaccination equals or exceeds that from prior maternal genital infection in murine models

Abstract Neonates are vulnerable to poor outcomes from herpes simplex virus (HSV), but maternal infection eliciting non-sterilizing immunity prior to delivery provides some protection. We are therefore pursuing birthing parent vaccination with nucleoside-modified mRNA-lipid nanoparticles (mRNA-LNPs) to prevent neonatal herpes. Our trivalent vaccine encodes HSV type 2 (HSV-2) proteins involved in attachment and immune evasion (gC2, gD2, and gE2). We have shown that this vaccine protects against genital HSV and neonatal HSV-2 in mice. Here, we tested how well murine dam vaccination prior to pregnancy protects pups against HSV type 1 (HSV-1) challenge compared to prior maternal intravaginal HSV-1 infection. Dams were immunized intramuscularly with the HSV-2 trivalent mRNA-LNP vaccine or a control immunogen (PolyC RNA-LNP), or were infected intravaginally with HSV-1 (HSV-1 ivag). Pups were challenged intranasally with HSV-1 on the 3rd day of life. Pups born to dams previously immunized or infected survived through 28 days (mRNA 95% vs. HSV-1 ivag 96%, N.S.; vs. PolyC 13%, p<0.0001). Likewise, they were protected from HSV-1 dissemination to the brain, lung, liver, spleen, and kidney by plaque assay (mRNA 2/45 organs affected vs. HSV-1 ivag 6/20, p=0.0083; vs. PolyC 69/80, p<0.0001). Additionally, fewer organs showed necrosis by histopathology of brain, lung, and liver, though not statistically significant, and fewer mRNA and HSV-1 ivag pups had detectable HSV-1 DNA in the trigeminal ganglia by qPCR (mRNA 6/30 vs. HSV-1 ivag 7/26, N.S.; vs. PolyC 17/18, p<0.0001). These studies demonstrate that the mRNA vaccine provides comparable to improved protection against neonatal HSV-1 challenge versus prior maternal HSV-1 intravaginal infection. AD was supported by NIH NIAID T32 AI118684. HMF, SA, GHC, and DW were supported by NIH NIAID R01 AI139618 and an unrestricted grant from BioNTech SE. KPE was supported by NIH T32 NS007180. The funders had no input or influence on the content of this abstract.

Biological Effect of Quercetin in Repairing Brain Damage and Cerebral Changes in Rats: Molecular Docking and In Vivo Studies.

This study examined the protective effect of quercetin against high-altitude-induced brain damage in rats. A molecular docking study was performed to investigate the potential effect of quercetin in reducing brain damages through its ability to target the oxidative stress enzymes. Biomarker assessment screening assays were also performed then followed by in vivo studies. Three groups of rats were divided into the control group, an untreated animal model group with induced brain damage, and finally, the quercetin treated group that received quercetin dose equal to 20 mg/kg of their body weights. Molecular docking studies and biomarker assessment screening assays proved the potential effect of quercetin to affect the level of representative biomarkers glutathione (GSH), glutathione reductase (GR), glutathione-S-transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA). Additionally, the protective effect of quercetin against high altitude, low pressure, and low oxygen was also investigated by exploring the brain histopathology of experimental rats. Brain damage was observed in the untreated animal model group. After treatment with quercetin, the cerebral edema in the brain tissues was improved significantly, confirming the protective effects of quercetin. Therefore, quercetin can be used as a natural food additive to protect from the highaltitude-induced brain damage.

Effect of diet supplemented with African Star Apple Fruit Pulp on purinergic, cholinergic and monoaminergic enzymes, TNF-α expression and redox imbalance in the brain of hypertensive rats

ABSTRACT Objective This study examined whether diet supplemented with African star apple fruit pulp (FP) can mitigate the effect of high blood pressure on brain neurochemicals, histopathology and expression of genes linked with neuroinflammation. Methods Rats were administered with cyclosporine (25 mg/kg.bw) to induce hypertension and were fed with or without FP supplemented diet. Purinergic (Nucleoside triphosphate diphosphohydrolases [NTPdase] and adenosine deaminase [ADA]) cholinergic (acetylcholinesterase [AChE]) and monoaminergic (monoamine oxidase-B) enzymes were assessed in treated and untreated hypertensive rats’ brains. Oxidative stress biomarkers (catalase, glutathione-S-transferase, thiols, reactive oxygen species [ROS] and malondialdehyde [MDA]), as well as AChE, tumour necrosis factor and receptor (TNF-α and TNF-α-R) expression, were also determined. Results FP supplemented diet significantly reduced NTPdase and ADA activities and increased Na+/K+-ATPase activities in hypertensive rats’ brains compared to the untreated group. Furthermore, FP reduced acetylcholinesterase and monoamine oxidase-B activities compared to the hypertensive group. Redox imbalance was observed in hypertensive rats with inhibition of antioxidant enzymes and high levels of ROS and MDA. However, FP supplemented diet improved antioxidant enzymes, reduced ROS and MDA production in the brain of hypertensive rats. High blood pressure also triggered upregulation of AChE, TNF-α and TNF-α-R while feeding with FP supplemented diet downregulated the genes. Conclusion This study demonstrates the neuroprotective role of FP supplemented diet against alterations in neurochemicals associated with Alzheimer’s disease, oxidative stress-induced neuronal damage and expression of genes linked with neuroinflammation. Moreover, studies on animal behaviour and human subjects are required to confirm these beneficial effects.

Effect of vestibular stimulation on cold water stress-induced neurological changes in Wistar rats

The current study was undertaken to see the effects of cold-water stress on the brain and to evaluate the beneficial effect of vestibular stimulation on stress-induced brain changes. Healthy, male, Wistar rats, weighing 180 to 250 gm with 3-6 months of age, were used for the study. Stress was induced by making the animals swim in cold water maintained at 100C for 30 min a day, for 14 days. Following cold water swimming stress, bilateral hot water caloric vestibular stimulation was given to the animals using 410C temperature water for 15 days. Rats were sacrificed and histopathological brain changes were studied by Hematoxylin & Eosin staining. Serum corticosterone level has increased significantly after cold water swimming stress (p<0.01). Corticosterone was less in animals that received caloric vestibular stimulation in comparison with the animals which did not receive caloric vestibular stimulation (p<0.05). Coldwater swimming stress had induced focal neuronal atrophy, nuclear pyknosis with congested blood vessels and infiltration of mononuclear inflammatory cells in the hippocampus and hypothalamus. Stressed animals that received caloric vestibular stimulation recovered well and showed the cerebral cortex with the normal neuroglial arrangement. Hypothalamus showed normal morphology and the hippocampus showed a pyramidal layer with a normal thickness in comparison to the animals which did not receive caloric vestibular stimulation. We conclude Caloric vestibular stimulation was effective in reversing the cold-water stress-induced serum corticosterone and histopathological changes in the brain.

Effect of ethanolic extract of Fagonia cretica on BPA induced genotoxicity and histopathology in brain and testis tissues of rats

Effect of ethanolic extract of Fagonia cretica on BPA induced genotoxicity and histopathology in brain and testis tissues of rats

Posttraumatic midazolam administration does not influence brain damage after experimental traumatic brain injury

BackgroundThe benzodiazepine midazolam is a γ-aminobutyric acid (GABA)-A receptor agonist frequently used for sedation or stress control in patients suffering from traumatic brain injury (TBI). However, experimental studies on benzodiazepines have reported divergent results, raising concerns about its widespread use in patients. Some studies indicate that benzodiazepine-mediated potentiation of GABAergic neurotransmission is detrimental in brain-injured animals. However, other experimental investigations demonstrate neuroprotective effects, especially in pretreatment paradigms. This study investigated whether single-bolus midazolam administration influences secondary brain damage post-TBI.MethodsTwo different midazolam dosages (0.5 and 5 mg/kg BW), a combination of midazolam and its competitive antagonist flumazenil, or vehicle solution (NaCl 0.9%) was injected intravenously to mice 24 h after experimental TBI induced by controlled cortical impact. Mice were evaluated for neurological and motor deficits using a 15-point neuroscore and the rotarod test. Histopathological brain damage and mRNA expression of inflammatory marker genes were analyzed using quantitative polymerase chain reaction three days after insult.ResultsHistological brain damage was not affected by posttraumatic midazolam administration. Midazolam impaired functional recovery, and this effect could not be counteracted by administering the midazolam antagonist flumazenil. An increase in IL-1β mRNA levels due to postinjury application of midazolam was reversible by flumazenil administration. However, other inflammatory parameters were not affected.ConclusionsThis study merely reports minor effects of a postinjury midazolam application. Further studies focusing on a time-dependent analysis of posttraumatic benzodiazepine administration are required.

Protective Effect of Portulaca oleracea Extract Against Lipopolysaccharide-Induced Neuroinflammation, Memory Decline, and Oxidative Stress in Mice: Potential Role of miR-146a and miR-let 7.

Neuroinflammation is an adaptive immune response to the central nervous system (CNS) injury induced by infection or toxins. MicroRNAs (miRs) showed critical roles in neuroinflammation as either proinflammatory or anti-inflammatory molecules. Interestingly, Portulaca oleracea (purslane) is an edible plant capable of ameliorating several diseases, including headache, burns, and diabetes; however, its effect on the neuroinflammation-associated miRs was not previously investigated. This study aimed to investigate the effect of aqueous purslane extract on the neuroinflammation induced by lipopolysaccharide (LPS) in mice and to identify its effect on animal cognition, oxidative stress, and expressions of miR-146a and miR-let 7. Adult mice were divided into the following groups: Normal group, LPS group, and Purslane+LPS group. Novel target recognition test, brain histopathology, and measurement of oxidative stress and inflammatory markers were performed. The results showed that LPS group exhibited significant decline in the cognitive memory, brain histopathological injury and a decrease in the number of intact neurons compared to the normal group. Furthermore, the LPS group showed a significant increase in malondialdehyde concentration, whereas superoxide dismutase and catalase activities were decreased. The LPS group also showed an increase in the inflammatory markers tumor necrosis factor-α and nuclear factor kappa B and downregulation of miR-146a and miR-let 7 expressions in the brain cells compared to the normal group, P value <.05. Interestingly, all these changes were reversed by administration of the aqueous purslane extract. In conclusion, the aqueous purslane extract protected from LPS-induced neuroinflammation and memory decline in mice through antioxidant and anti-inflammatory effect where upregulation of miR-146a and miR-1et 7 expressions was involved.

Protective efficacy of rutin against acrylamide-induced oxidative stress, biochemical alterations and histopathological lesions in rats.

Acrylamide is a well-known neurotoxicant and carcinogen. Apart from industrial exposure, acrylamide is also found in different food products. The present study deals with in vivo experiment to test the protective effect of rutin against acrylamide induced toxicity in rats. The study was carried out on female rats with exposure of acrylamide at the dose of 38.27mg/kg body weight, orally for 10days followed by the therapy of rutin (05, 10, 20 and 40mg/kg orally), for three consecutive days. All animals were sacrificed after 24h of last treatment and various biochemical parameters in blood and tissue were investigated. Histopathology of liver, kidney and brain was also done. On administration of acrylamide for 10days, neurotoxicity was observed in terms of decreased acetylcholinesterase activity and oxidative stress was observed in terms of increased lipid peroxidation, declined level of reduced glutathione, antioxidant enzymes (superoxide dismutase and catalase) in liver, kidney and brain. Acrylamide exposure increased the activities of serum transaminases, lipid profile, bilirubin, urea, uric acid and creatinine in serum indicating damage. Our experimental results conclude that rutin showed remarkable protection against oxidative DNA damage induced by acrylamide, which may be due to its antioxidant potential.

Clinical utility of brain biopsy for presumed CNS relapse of systemic lymphoma.

The objective of this study was to determine the frequency with which brain biopsy for presumed CNS relapse of systemic hematological malignancies yields new, actionable diagnostic information. Hematological malignancies represent a disparate group of genetic and histopathological disorders. Proclivity for brain involvement is dependent on the unique entity and may occur synchronously or metasynchronously with the systemic lesion. Diffuse large B-cell lymphomas (DLBCLs) have a high propensity for brain involvement. Patients in remission from systemic DLBCL may present with a lesion suspicious for brain relapse. These patients often undergo brain biopsy. The authors' a priori hypothesis was that brain biopsy in patients with a history of systemic DLBCL and a new brain MRI lesion would have lower diagnostic utility compared with patients with non-DLBCL systemic malignancies. The authors performed a retrospective review of patients who underwent brain biopsy between 2000 and 2019. Inclusion criteria were patients ≥ 18 years of age with a prior systemic hematological malignancy in remission presenting with a new brain MRI lesion concerning for CNS relapse. Patients with a history of any CNS neoplasms, demyelinating disorders, or active systemic disease were excluded. The main outcome was the proportion of patients with a distinct histopathological brain diagnosis compared with the systemic malignancy. The authors secondarily assessed overall survival, procedure-related morbidity, and 30-day mortality. Sixty patients met inclusion criteria (40 males and 20 females); the median age at brain biopsy was 67 years (range 23-88 years). The median follow-up was 8.5 months (range 0.1-231 months). Thirty-nine (65.0%) patients had DLBCL and 21 (35%) had non-DLBCL malignancies. Thirty-five of 36 (97.2%) patients with prior systemic DLBCL and a diagnostic biopsy had histopathological confirmation of the original systemic disease versus 0 of 21 patients with non-DLBCL systemic malignancies (p < 0.001). Morbidity and 30-day mortality were 8.3% and 10.0%, respectively; 2 of 6 30-day mortalities were directly attributable to the biopsy. The median overall survival following brain biopsy was 10.8 months. Patients with a history of systemic DLBCL and presumed CNS relapse gained minimal clinical benefit from brain biopsy but were at high risk of morbidity and mortality. In patients with a history of non-DLBCL systemic malignancies, brain biopsy remained critical given the high likelihood for discovery of distinct diagnostic entities. It was determined that patients with a prior systemic DLBCL and presumed brain relapse should likely receive empirical therapy obviating treatment delay and the risks of brain biopsy.

Comparison of the effects of argan and nigella oils on malathion-induced cognitive-behavioral alterations and brain histopathology in male Wistar rats

Comparison of the effects of argan and nigella oils on malathion-induced cognitive-behavioral alterations and brain histopathology in male Wistar rats

Aerobic Exercise Mediated Increase in BDNF Expression Ameliorates Depression in Propylthiouracil-Induced Hypothyroidism in Adult Rats.

• Hypothyroidism is associated with depressive symptoms. • Swimming exercise for 4 weeks alleviated depressive behavior in hypothyroid rats. • The enhanced irisin/BDNF axis activity following moderate aerobic exercise was positively correlated with climbing time in forced swimming test and with brain serotonergic system activity. • It is concluded that moderate aerobic exercise alleviated hypothyroidism-associated depression via increased BDNF expression. : The prevalence of depression with hypothyroidism is high. : To study the ability of aerobic exercise to improve hypothyroidism associated depression and to explore the underlying mechanisms. 21 adult male rats, allocated in three groups; Euthyroid, Hypothyroid (oral propyl-thiouracil for 45 days), Exercise-treated hypothyroid group (30 minutes, swimming, 4 weeks). Forced swim test and histopathological brain examination were performed. Serum free T3, T4, TSH, irisin, brain neurochemical, oxidant-antioxidant and apoptotic markers were measured . : Swimming exercise increased serum T3, T4, climbing and swimming times, brain serotonin, BDNF expression, glutathione peroxidase, antiapoptotic Bcl-2 and serum irisin levels and decreased TSH, immobility time, MDA, BAX/Bcl-2 ratio. Climbing time was positively correlated with BDNF, serotonin and T3. : Moderate aerobic exercise alleviated hypothyroidism-associated depression, via increased BDNF expression, which enhances hippocampal neurogenesis, serotonergic system activity and combat neuronal apoptosis.

Iron status, immune system, and expression of brain divalent metal transporter 1 and dopamine receptors D1 interrelationship in Parkinson’s disease and the role of grape seed and green coffee bean extracts and quercetin in mitigating the disease in rats

Introduction: Parkinson’s disease (PD) is a neurodegenerative disease with a prevalence of 1% in the elderly worldwide. The aim of the research is to study the interrelationship of iron status, the immune system including inflammatory cytokines, brain divalent metal transporter 1 (DMT1), and dopamine receptors D1 (DRD1) in a PD rat model. The potential protective effects of grape seed and green coffee bean ethanol extracts and quercetin were also studied. Methods: Phenolic and flavonoid contents of grape seed and green coffee bean and in vitro free radicals scavenging activities of the extracts and quercetin were determined. Male rats were divided into five groups. Group 1 served as normal control (NC), group 2 represented Parkinsonian control (PC). Groups 3, 4, and 5 were the test groups treated by daily oral green coffee bean, grape seed extracts, and quercetin, respectively. PD was induced by rotenone in groups 2 to 5. Brain oxidative stress, DMT1, and DRD1 expressions, and histopathology were assessed. Parameters of the immune system, represented by plasma interferon-gamma (IFNγ) and CD4, and brain tumor necrosis factor-alpha (TNF-α) along with iron status were also determined. Results: Phenolic and flavonoid contents of green coffee bean were high compared to grape seed (P &lt; 0.05). Quercetin experienced the highest in-vitro free radicals scavenging activities. Iron deficiency anemia, together with elevated IFNγ, TNF-α, DMT1 expressions, and brain malondialdehyde (MDA) were demonstrated in PC compared to NC (P &lt; 0.05). Also, reduction in CD4 and brain reduced-glutathione (GSH) (P &lt; 0.05) were noticed in PC with brain histopathological alterations. Different treatments showed variable improvements in the majority of parameters (P &lt; 0.05) and brain histopathology. Conclusion: Iron deficiency anemia might result from cytokine elevation in PD. Reduced DRD1 and altered immune system including cytokines together with increased brain DMT1 might induce neurodegeneration in PD. Different treatments showed variable neuroprotective effects through modulation of inflammation, oxidative stress, immune system, iron status, DMT1, and DRD1.

Histopathology of Brain and Spleen of Freshwater Teleost Anabas testudineus (Bloch, 1792) Induced by Organochlorine Insecticide Endosulfan

Endosulfan is an important environmental pollutant that is a pesticide of organochlorine. The 24, 48, 72 and 96h median lethal concentrations of endosulfan (35 EC) were assessed by an acute static renewal test. The sublethal concentration taken for the present study is one-tenth of the 96h LC50 and fish were exposed to that concentration (1.69 ppb) for 30 days. The histopathological observations revealed the presence of catecholamine neurons in the optic tectum and severe depletion of the layer stratum grisum periventricular. An altered pattern of neurons as an “interrupted string of pearls” was noticed in the posterior tuberal nucleus. From the present study, we could conclude that endosulfan is a serious toxicant that even affects the vital organs like the brain of vertebrates. Histology of the spleen showed necrosis in red pulp, hyperplasia and exudate in white pulp and an increased number of melanomacrophage centers (MMC) of the exposed fish species. Based on the results of this study, it is concluded that endosulfan is highly toxic to edible freshwater fish Anabas testudineus. Subsequently, damage to the structures of cells and tissues and histopathology of target organs comprise a significant parameter to be considered in evaluating the toxic possibility of contaminations on living organisms in various environmental conditions and represent the time exposure to which organisms are subjected.

BrainApp: Using near-patient sensing through a mobile app and machine learning in brain tumour patients

Abstract Aims 1. To assess the feasibility, acceptability, and performance of a mobile app, 'BRIAN', developed by The Brain Tumour Charity (BTC), in collecting data on quality of life (QOL), activity and sleep, for predicting disease progression in adult brain tumour patients. 2. To generate a prospectively collected dataset of patient measures obtained through mobile devices in brain tumour patients and healthy volunteers. 3. To assess compliance and performance of micro-challenges (hand coordination, visual memory, speech and facial features) in study participants using a mobile application. 4. To assess differences and systematic variation in micro-challenge performance between healthy volunteers and brain tumour patients. 5. To assess factors associated with micro-challenge performance in brain tumour patients, the relationship between micro-challenges and standard measures of QoL and disease progression. 6. To assess the diagnostic performance of different machine learning models in detecting brain tumour progression. Method This abstract describes the protocol for a multi-centre observational non-randomised phase II trial for adult brain tumour patients and healthy volunteers in the UK. Participants will use the BRIAN mobile app, developed by BTC to help individuals cope with a brain tumour, and share their journey with both researchers and clinicians. Participants will be required to enter information on their medical background, mood, and QOL; have the option to link fitness trackers to the app; as well as perform mini-games which assess speech, coordination, facial features and reaction time. Patients will have their brain imaging and histopathology report submitted to the sponsor. We will then investigate the correlation and temporal relation of these multimodal data with conventional measures of disease progression. We will use traditional statistical methods initially (i.e. descriptive statistics and multilevel modelling), which will then inform the development of a machine learning model in predicting brain tumour progression. Results The BRIAN app is currently being beta-tested by healthy volunteers from the Computational Oncology Lab, Imperial College London. We are in the process of obtaining ethical approval for the trial. Conclusion This study may enable the development of a tool that allows us to detect earlier signs of disease progression, and so offer earlier treatment and preservation of quality of life; and hence the best course of action. Such a tool would also be non-invasive, cheap, quick, and can be used by patients in the comfort of their own homes.

Vestibular Stimulation as An Interventional Approach for Cold Water Stress Induced Immunological and Histopathological Changes in Rats

Background: Chronic exposure to stress results in immuno-suppression. The present study was carried out to explore the therapeutic benefits of vestibular stimulation on the immune system of stress-induced Wistar rats. Methods: Stress was intervened in the Wistar rats by cold water swimming method for a period of 14 days. Following stress, caloric vestibular stimulation was induced in the rats by irrigating external auditory meatus bilaterally with hot water (temperature 41oC) for 2 minutes for a period of 15 days and 30 days in respective groups. At the end of the experiment, blood samples were obtained and serum corticosterone, Interleukin 2 (IL2), Immunoglobulin M (IgM) levels were analyzed using ELISA method and histopathology of brain was assessed. Brain CD4 and CD8 cells were analyzed by Immunohistochemistry. Result: Stress significantly increased serum corticosterone, IL2 levels and reduced IgM levels. Stress group showed increased dendritic arborization in prefrontal cortex, neuronal atrophy, nuclear pyknosis with congested blood vessels in hippocampus and mononuclear cell inflammatory infiltrate in hypothalamus. Brain extravascular CD4 and CD8 showed positive in stress group. Caloric vestibular stimulation effectively reduced serum corticosterone levels, histopathological changes, brain extravascular CD4 and CD8 cells and improved IgM in the present study.