The Protective Mechanism for the Blood–Brain Barrier Induced by Aminoguanidine in Surgical Brain Injury in Rats

This study was performed to investigate the mechanism of blood–brain barrier (BBB) permeability change, which was induced by aminoguanidine (AG) after surgical brain injury (SBI) in rats. Compared to control group, AG (150 mg/kg, i.p.) significantly reduced Evans blue extravasation into brain tissue at 24 h after surgical resection, it also induced a 32% decrease of malondialdehyde (MDA) values and a 1.1-fold increase of the glutathione (GSH) levels at 12 h after injury. The expression of inducible nitric oxide synthase (iNOS) reached the peak value at 24 h after SBI, which was significantly attenuated after AG treatment. In addition, ZO-1 protein was up-regulated by AG (150 mg/kg) treatment at 24 h after SBI. Our results indicated that AG could protect the BBB after SBI, which could be correlated with antioxidative property, the down-regulation of iNOS and up-regulation of tight junction protein expression.     

Are Structural Changes Induced by Lithium in the HIV Brain Accompanied by Changes in Functional Connectivity?

Lithium therapy has been shown to affect imaging measures of brain function and microstructure in human immunodeficiency virus (HIV)-infected subjects with cognitive impairment. The aim of this proof-of-concept study was to explore whether changes in brain microstructure also entail changes in functional connectivity. Functional MRI data of seven cognitively impaired HIV infected individuals enrolled in an open-label lithium study were included in the connectivity analysis. Seven regions of interest (ROI) were defined based on previously observed lithium induced microstructural changes measured by Diffusion Tensor Imaging. Generalized partial directed coherence (gPDC), based on time-variant multivariate autoregressive models, was used to quantify the degree of connectivity between the selected ROIs. Statistical analyses using a linear mixed model showed significant differences in the average node strength between pre and post lithium therapy conditions. Specifically, we found that lithium treatment in this population induced changes suggestive of increased strength in functional connectivity. Therefore, by exploiting the information about the strength of functional interactions provided by gPDC we can quantify the connectivity changes observed in relation to a given intervention. Furthermore, in conditions where the intervention is associated with clinical changes, we suggest that this methodology could enable an interpretation of such changes in the context of disease or treatment induced modulations in functional networks.     

Post-Seizure α-Tocopherol Treatment Decreases Neuroinflammation and Neuronal Degeneration Induced by Status Epilepticus in Rat Hippocampus

Vitamin E (as α-tocopherol, α-T) was shown to have beneficial effects in epilepsy, mainly ascribed to its antioxidant properties. Besides radical-induced neurotoxicity, neuroinflammation is also involved in the pathophysiology of epilepsy, since neuroglial activation and cytokine production exacerbate seizure-induced neurotoxicity and contribute to epileptogenesis. We previously showed that α-T oral supplementation before inducing status epilepticus, markedly reduces astrocytic and microglial activation, neuronal cell death and oxidative stress in the hippocampus, as observed 4 days after seizure. In order to evaluate the possibility that such a neuroprotective and anti-inflammatory effect may also provide a strategy for an acute intervention in epilepsy, in this study, seizures were induced by single intaperitoneal injection of kainic acid and, starting from 3 h after status epilepticus, rats were treated with an intraperitoneal bolus of α-T (250 mg/kg b.w.; once a day) for 4 days, that was the time after which morphological and biochemical analyses were performed on hippocampus. Post-seizure α-T administration significantly reduced astrocytosis and microglia activation, and decreased neuron degeneration and spine loss; these effects were associated with the presence of a lowered lipid peroxidation in hippocampus. These results confirm and further emphasize the anti-inflammatory and neuroprotective role of α-T in kainic acid-induced epilepsy. Moreover, the findings show that post-seizure treatment with α-T provides an effective secondary prevention against post-seizure inflammation-induced brain damages and possibly against their epileptogenic effects.     

Morphofunctional Analysis of Effect of Short-Term Sleep Deprivation on the Wakefulness–Sleep Cycle in Young and Adult Rats

The work presents comparative data on changes of neurophysiological, time characteristics of the wakefulness–sleep cycle (WSC) and morphofunctional state of neurosecretory cells in supraoptic nucleus of the hypothalamus, which develop under influence of a 6-h long sleep deprivation in adult and one-month old rats. It is shown that the rebound of sleep develops in adult animals with a delay, after the 3rd hour and is characterized by a moderate increase of portions of slow-wave (SSP) and fast-wave (FSP) sleep phases in WSC and by a decrease of the wakefulness portion. Morphological analysis of the hypothalamus nonapeptidergic system has revealed a rise of content of neurosecretory material in fibers of supraoptic nucleus cells an in area of supraoptic-pituitary tract, as well as marked hyperemia that indicates activation of processes of secretion of neurohormones into the general blood flow; these reactions are similar to reactions of this system to stress. In rat pups the sleep rebound develops in 0.5 h after the end of the deprivation procedure and is characterized by more pronounced, statistically significant changes in WSC. Individual WSC become very short and almost all of them are completed with episodes of FSP. A statistically significant rise of power of the -wave band in electrogram spectra of hippocampus and somatosensory cortex in SSP, whereas peak of the activity in FSP is shifted to -waves. Ratios of SSP and FSP to wakefulness in individual WSC in mature animals increase after the deprivation 1.53 and 1.85 times, while they are elevated in one-month old animals 5.25 and 6.75 times, respectively. The obtained morphofunctional data allow believing that deprivation is the stress factor of low intensity for adult animals, whereas it may be considered as the stress action of intermediate and even high intensity for rat pups, which changes essentially the interrelations in WSC. Participation of central mechanisms of regulation of sleep and vigilance, which provide processes of compensation of damaging action of deprivation on WSC in the maturing animals, is discussed.     

Pale Body-Like Inclusion Formation and Neurodegeneration following Depletion of 26S Proteasomes in Mouse Brain Neurones are Independent of α-Synuclein

Parkinson’s disease (PD) is characterized by the progressive degeneration of substantia nigra pars compacta (SNpc) dopaminergic neurones and the formation of Lewy bodies (LB) in a proportion of the remaining neurones. α-synuclein is the main component of LB, but the pathological mechanisms that lead to neurodegeneration associated with LB formation remain unclear. Three pivotal elements have emerged in the development of PD: α-synuclein, mitochondria and protein degradation systems. We previously reported a unique model, created by conditional genetic depletion of 26S proteasomes in the SNpc of mice, which mechanistically links these three elements with the neuropathology of PD: progressive neurodegeneration and intraneuronal inclusion formation. Using this model, we tested the hypothesis that α-synuclein was essential for the formation of inclusions and neurodegeneration caused by 26S proteasomal depletion. We found that both of these processes were independent of α-synuclein. This provides an important insight into the relationship between the proteasome, α-synuclein, inclusion formation and neurodegeneration. We also show that the autophagy-lysosomal pathway is not activated in 26S proteasome-depleted neurones. This leads us to suggest that the paranuclear accumulation of mitochondria in inclusions in our model may reflect a role for the ubiquitin proteasome system in mitochondrial homeostasis and that neurodegeneration may be mediated through mitochondrial factors linked to inclusion biogenesis.     

Immunohistochemical Study of Immunophilin 1–15 Fragment in Intact Frog Brain,and in the Brain and Spinal Cord of Intact and Spinal Cord Hemisectioned Rats

Previously by immunohistochemical technique the distribution of immunophilin 1–15 fragment (IphF) isolated from bovine hypothalamus was examined in various tissues (heart, lung), including immune system organs (spleen and thymus) of intact rats. IphF-like immunoreactivity (IphF-LI) was revealed in several cell types: lymphocytes, monocytes, macrophages and mast cells. In the present study the immunohistochemical localization of IphF was examined in intact rat and frog brains. In rat brain several cell groups concentrated particularly in the supraoptic nucleus (SON) of hypothalamus, medulla oblongata (reticular formation, olives, hypoglossal and facial motor nuclei) and cerebellum (lateral cerebellar nucleus) demonstrated IphF-LI. In frog hypothalamus (SON) the same working dilution (1:5000) of IphF-antiserum revealed very strong immunoreactivity. In the paraventricular nucleus (PVN) IphF-LI varicosities were scattered around the immunonegative cells. The second cell groups showing IphF-LI in the frog brain were gliocytes (mainly the astrocytes). Besides, IphF distribution was investigated in rats subjected to hemisection of spinal cord (SC) with and without administration of proline-rich polypeptide (PRP). PRP was isolated from bovine neurohypophysis neurosecretory granules, produced by magnocellular nuclei of hypothalamus. Hemisection of SC led to changes of IphF distribution in the hypothalamus. In PRP treated animals IphF showed no immunoreactivity. PRP is suggested to act as a neurotransmitter and neuroregulator.     

Depletion of Vitamin E Increases Amyloid �� Accumulation by Decreasing Its Clearances from Brain and Blood in a Mouse Model of Alzheimer Disease

Increased oxidative damage is a prominent and early feature in Alzheimer disease. We previously crossed Alzheimer disease transgenic (APPsw) model mice with α-tocopherol transfer protein knock-out (Ttpa^−/−) mice in which lipid peroxidation in the brain was significantly increased. The resulting double-mutant (Ttpa^−/−APPsw) mice showed increased amyloid β (Aβ) deposits in the brain, which was ameliorated with α-tocopherol supplementation. To investigate the mechanism of the increased Aβ accumulation, we here studied generation, degradation, aggregation, and efflux of Aβ in the mice. The clearance of intracerebral-microinjected ¹²⁵I-Aβ_1–40 from brain was decreased in Ttpa^−/− mice to be compared with wild-type mice, whereas the generation of Aβ was not increased in Ttpa^−/−APPsw mice. The activity of an Aβ-degrading enzyme, neprilysin, did not decrease, but the expression level of insulin-degrading enzyme was markedly decreased in Ttpa^−/− mouse brain. In contrast, Aβ aggregation was accelerated in Ttpa^−/− mouse brains compared with wild-type brains, and well known molecules involved in Aβ transport from brain to blood, low density lipoprotein receptor-related protein-1 (LRP-1) and p-glycoprotein, were up-regulated in the small vascular fraction of Ttpa^−/− mouse brains. Moreover, the disappearance of intravenously administered ¹²⁵I-Aβ_1–40 was decreased in Ttpa^−/− mice with reduced translocation of LRP-1 in the hepatocytes. These results suggest that lipid peroxidation due to depletion of α-tocopherol impairs Aβ clearances from the brain and from the blood, possibly causing increased Aβ accumulation in Ttpa^−/−APPsw mouse brain and plasma.     

Does the Biosocial Model Explain the Emergence of Status Differences in Conversations among Unacquainted Men?

Fifteen triads of unacquainted men conversed for ten minutes while stress was measured in real time by pulse rate and thumb blood volume (TBV). Salivary measures of testosterone (T), cortisol (C), and the stress-related enzyme alpha-amylase (AA) were measured at the beginning and end of the session. Fully or partially transitive status hierarchies formed in 14 triads. (Highest ranked man was scored 1, lowest 3, with ties allowed.) Ten of the triads participated in Study 1, where nothing was at stake in the casual conversation. Five additional triads were run in Study 2, intended to introduce competition by offering a $20 reward to the man afterward chosen as having led the conversation. Most results from the two studies are similar, suggesting that the $20 reward had little effect. Combining studies, pulse and TBV show that conversation is more stressful than watching a video beforehand. Within the conversation, speaking turns are more stressful than listening turns, especially among the lowest ranked men, less so among those higher in rank. This supports a stress-based mechanism for status allocation among humans. Apparently, human speech is a form of status signaling, homologous with nonlinguistic status signals used by other primates, as posited by the “biosocial model.” The biosocial model also posits that a physiological substrate (T, C, and AA) is related to dominance or status. Predicted effects are not replicated here, except for an inverse relationship between the stress enzyme AA and status. The mostly null results, obtained from conversations where there was little or nothing at stake, suggest that T and C (and their interaction) are not relevant to emergent status in the absence of serious competition.     

Protection of TGF-β1 against Neuroinflammation and Neurodegeneration in Aβ1–42-Induced Alzheimer’s Disease Model Rats

Neuroinflammation has been reported to be associated with Alzheimer’s disease (AD) pathogenesis. Neuroinflammation is generally considered as an outcome of glial activation; however, we recently demonstrated that T helper (Th)17 cells, a subpopulation of proinflammatory CD4+ T cells, are also involved in AD pathogenesis. Transforming growth factor (TGF)-β1, a cytokine that can be expressed in the brain, can be immunosuppressive, but its effects on lymphocyte-mediated neuroinflammation in AD pathogenesis have not been well addressed. In the current study we administered TGF-β1 via intracerebroventricle (ICV) and intranasal (IN) routes in AD model rats to investigate its antiinflammatory and neuroprotective effects. The AD rat model was prepared by bilateral hippocampal injection of amyloid-β (Aβ)_1–42. TGF-β1 was administered via ICV one hour prior to Aβ_1–42 injection or via both nares seven days after Aβ_1–42 injection. ICV administration of TGF-β1 before Aβ_1–42 injection remarkably ameliorated Aβ_1–42-induced neurodegeneration and prevented Aβ_1–42-induced increases in glia-derived proinflammatory mediators (TNF-α, IL-1β and iNOS), as well as T cell-derived proinflammatory cytokines (IFN-γ, IL-2, IL-17 and IL-22), in the hypothalamus, serum or cerebrospinal fluid (CSF) in a concentration-dependent manner. TGF-β1 pretreatment also prevented Aβ_1–42-induced decreases in the neurotrophic factors, IGF-1, GDNF and BDNF, and in the antiinflammatory cytokine, IL-10. Similarly, IN administration of TGF-β1 after Aβ_1–42 injection reduced neurodegeneration, elevation of proinflammatory mediators and cytokines, and reduction of neurotrophic and antiinflammatory factors, in the hypothalamus, serum or CSF. These findings suggest that TGF-β1 suppresses glial and T cell-mediated neuroinflammation and thereby alleviates AD-related neurodegeneration. The effectiveness of IN administered TGF-β1 in reducing Aβ_1–42 neurotoxicity suggests a possible therapeutic approach in patients with AD.     

Could Selenium Administration Alleviate the Disturbances of Blood Parameters Caused by Lithium Administration in Rats?

Lithium is widely used in medicine, but its administration can cause numerous side effects. The present study aimed at the evaluation of the possible application of selenium, an essential and antioxidant element, as a protective agent against lithium toxicity. The experiment was performed on four groups of Wistar rats: I (control)—treated with saline, II (Li)—treated with lithium (Li₂CO₃), III (Se)—treated with selenium (Na₂SeO₃) and IV (Li?+?Se)—treated with lithium and selenium (Li₂CO₃ and Na₂SeO₃) in the form of water solutions by stomach tube for 6 weeks. The following biochemical parameters were measured: concentrations of sodium, potassium, calcium, magnesium, phosphorus, iron, urea, creatinine, cholesterol, glucose, total protein and albumin and activities of alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase in serum as well as whole blood superoxide dismutase and glutathione peroxidase. Morphological parameters such as red blood cells, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, platelets, white blood cells, neutrophils as well as lymphocytes were determined. Lithium significantly increased serum calcium and glucose (2.65?±?0.17 vs. 2.43?±?0.11; 162?±?31 vs. 121?±?14, respectively), whereas magnesium and albumin were decreased (1.05?±?0.08 vs. 1.21?±?0.15; 3.85.?±?0.12 vs. 4.02?±?0.08, respectively). Selenium given with lithium restored these parameters to values similar to those observed in the control (Ca—2.49?±?0.08, glucose—113?±?26, Mg—1.28?±?0.09, albumin—4.07?±?0.11). Se alone or co-administered with Li significantly increased aspartate aminotransferase and glutathione peroxidase. The obtained outcomes let us suggest that the continuation of research on the application of selenium as an adjuvant in lithium therapy seems warranted.     

Changes in Expression of GABAA α4 Subunit mRNA in the Brain under Anesthesia Induced by Volatile and Intravenous Anesthetics

We investigated changes in levels of GABA_A receptor α4 subunit mRNA in the mouse brain after administration of volatile or i.v. anesthetic, by performing quantitative RT-PCR. We also performed immunohistochemical assays for c-fos-like protein. During deep anesthesia (which was estimated by loss of righting reflex) after administration of propofol, levels of GABA_A receptor α4 subunit mRNA in the hippocampus, striatum and diencephalons were significantly greater than those observed after administration of pentobarbital, midazolam or GOI (5.0% isoflurane and 70% nitrous oxide in oxygen). Under incomplete anesthesia, levels of GABA_A receptor α4 subunit mRNA were significantly increased by midazolam in all brain regions, and were significantly increased by pentobarbital in the posterior cortex and striatum. Expression of GABA_A receptor α4 subunit mRNA closely correlated with expression of c-fos-like protein. These results indicate that the GABA_A receptor α4 subunit plays an important role in regulating the anesthetic stage of i.v. anesthetics.     

Excitotoxicity in Rat’s Brain Induced by Exposure of Manganese and Neuroprotective Effects of Pinacidil and Nimodipine

Manganese (Mn) is an essential trace element for humans. However, manganism would be caused by excessive Mn. The mechanisms underlying excitotoxicity induced by manganism are poorly understood. As it is known to us, glutamate (Glu) is the most prevalent excitatory neurotransmitter. To determine the possible role of dysfunction of Glu transportation and metabolism in Mn-induced excitotoxicity, the rats were ip injected with different dose of MnCl₂ (0, 50, 100, and 200 μmol/kg), the levels of Mn and activities of GS, PAG, Na⁺-K⁺-ATPase, and Ca²⁺-ATPase in striatum were investigated. In addition, effect of 20.38 μmol/kg pinacidil (K⁺ channel opener) or 2.4 μmol/kg nimodipine (Ca²⁺ channel blocker) were studied at 200 μmol/kg MnCl₂. With dose-dependent inhibition of GS, Na⁺-K⁺-ATPase, and Ca²⁺-ATPase activities, increase of Mn levels and PAG activity were observed. Further investigation indicated that pre-treatment of pinacidil or nimodipine reversed toxic effect of MnCl₂ significantly. These results suggested that MnCl₂ could induce dysfunction of Glu transportation and metabolism by augmenting the excitotoxicity dose-dependently; pinacidil and nimodipine might antagonize manganese neurotoxicity.     

Ameliorated Effects of (−)-Epigallocatechin Gallate Against Toxicity Induced by Vanadium in the Kidneys of Wistar Rats

Obesity is a chronic disease characterized by excessive accumulation of body fat and the presence of metabolic disorders such as insulin resistance. In this sense, zinc is an important nutrient that stimulates insulin secretion and increases sensitivity to insulin. The aim of this study was to investigate the effect of zinc supplementation on insulin resistance in obese subjects through a systematic review of the available clinical trials. The search for articles was conducted using the PubMed, SciVerse Scopus, SciVerse ScienceDirect, and Cochrane databases, on May 25, 2016, by two authors independently. The recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed in the conduct of this review. The Cochrane Collaboration tool was used to assess the risk of bias of the trials included in this review. After screening of the articles, six clinical trials were included in this systematic review. The scientific evidence presented in this systematic review shows that zinc supplementation improves insulin resistance in obese individuals of both sexes.     

Characterization and Identification of Subpopulations of Mononuclear Preosteoclasts Induced by TNF-α in Combination with TGF-β in Rats

Osteoclasts are unique multinucleated cells formed by fusion of preosteoclasts derived from cells of the monocyte/macrophage lineage, which are induced by RANKL. However, characteristics and subpopulations of osteoclast precursor cells are poorly understood. We show here that a combination of TNF-α, TGF-β, and M-CSF efficiently generates mononuclear preosteoclasts but not multinucleated osteoclasts (MNCs) in rat bone marrow cultures depleted of stromal cells. Using a rat osteoclast-specific mAb, Kat1, we found that TNF-α and TGF-β specifically increased Kat1⁺c-fms⁺ and Kat1⁺c-fms⁻ cells but not Kat1⁻c-fms⁺ cells. Kat1⁻c-fms⁺ cells appeared in early stages of culture, but Kat1⁺c-fms⁺ and Kat1⁺c-fms⁻ cells increased later. Preosteoclasts induced by TNF-α, TGF-β, and M-CSF rapidly differentiated into osteoclasts in the presence of RANKL and hydroxyurea, an inhibitor of DNA synthesis, suggesting that preosteoclasts are terminally differentiated cells. We further analyzed the expression levels of genes encoding surface proteins in bone marrow macrophages (BMM), preosteoclasts, and MNCs. Preosteoclasts expressed itgam (CD11b) and chemokine receptors CCR1 and CCR2; however, in preosteoclasts the expression of chemokine receptors CCR1 and CCR2 was not up-regulated compared to their expression in BMM. However, addition of RANKL to preosteoclasts markedly increased the expression of CCR1. In contrast, expression of macrophage antigen emr-1 (F4/80) and chemokine receptor CCR5 was down-regulated in preosteoclasts. The combination of TNF-α, TGF-β, and M-CSF induced Kat1⁺CD11b⁺ cells, but these cells were also induced by TNF-α alone. In addition, MIP-1α and MCP-1, which are ligands for CCR1 and CCR2, were chemotactic for preosteoclasts, and promoted multinucleation of preosteoclasts. Finally, we found that Kat1⁺c-fms⁺ cells were present in bone tissues of rats with adjuvant arthritis. These data demonstrate that TNF-α in combination with TGF-β efficiently generates preosteoclasts in vitro. We delineated characteristics that are useful for identifying and isolating rat preosteoclasts, and found that CCR1 expression was regulated in the fusion step in osteoclastogenesis.     

Characterization and Modulation of Glucose Uptake in a Human Blood–Brain Barrier Model

The blood–brain barrier (BBB) plays a key role in limiting and regulating glucose access to glial and neuronal cells. In this work glucose uptake on a human BBB cell model (the hCMEC/D3 cell line) was characterized. The influence of some hormones and diet components on glucose uptake was also studied. ³H-2-deoxy-d-glucose ([³H]-DG) uptake for hCMEC/D3 cells was evaluated in the presence or absence of tested compounds. [³H]-DG uptake was sodium- and energy-independent. [³H]-DG uptake was regulated by Ca²⁺ and calmodulin but not by MAPK kinase pathways. PKC, PKA and protein tyrosine kinase also seem to be involved in glucose uptake modulation. Progesterone and estrone were found to decrease ³H-DG uptake. Catechin and epicatechin did not have any effect, but their methylated metabolites increased [³H]-DG uptake. Quercetin and myricetin decreased [³H]-DG uptake, and glucuronic acid-conjugated quercetin did not have any effect. These cells expressed GLUT1, GLUT3 and SGLT1 mRNA.     

Soy Isoflavone Antagonizes the Oxidative Cerebrovascular Injury Induced by β-Amyloid Peptides 1–42 in Rats

Numerous evidences have shown that the antioxidative properties of soy isoflavone (SIF) have beneficial effects on prophylaxis of neurodegeneration, however, the mechanism is still not fully illustrated. As cerebrovascular dysfunction could initiate a cascade of events leading to pathogenesis of Alzheimer’s disease, we tried to investigate whether SIF could protect the cerebrovascular system due to antagonizing oxidative damage induced by Aβ1–42 in present study. In addition, NF-E2-related factor 2 (Nrf2) signaling pathways in the cerebrovascular tissue of Wistar rats were investigated to identify the potential cerebrovascular protective targets of SIF. Research results showed that SIF reduced the excessive production of nitrotyrosine in cerebrovascular tissue induced by Aβ1–42, and maintained redox homeostasis by increasing the level of GSH and GSH/GSSG. Moreover, SIF could alleviate the down-regulation of Nrf2, γ-glutamylcysteine synthetase, Heme oxygenase-1 expressions in cerebrovascular tissue induced by Aβ1–42 and suppress the increase of Kelch like ECH protein-1 (Keap1). These data suggested that SIF might reduce the cerebrovascular oxidative damage induced by Aβ1–42 through regulating the Nrf2 signaling pathway. The mechanisms of SIF modulating the potential target Nrf2 might be associated with Keap1 expression.     

The Effect of Butylphthalide on the Brain Edema,Blood–Brain Barrier of Rats After Focal Cerebral Infarction and the Expression of Rho A

The aim of this study was to explore the effect of butylphthalide on the brain edema, blood–brain barrier of rats of rats after focal cerebral infarction and the expression of Rho A. A total of 195 sprague–dawley male rats were randomly divided into control group, model group, and butylphthalide group (40 mg/kg, once a day, by gavage). The model was made by photochemical method. After surgery 3, 12, 24, 72, and 144 h, brain water content was done to see the effect of butylphthalide for the cerebral edema. Evans blue extravasation method was done to see the changes in blood–brain barrier immunohistochemistry, and Western blot was done to see the expression of Rho A around the infarction. Compared with the control group, the brain water content of model group and butylphthalide group rats was increased, the permeability of blood–brain barrier of model group and butylphthalide group rats was increased, and the Rho A protein of model group and butylphthalide group rats was increased. Compared with the model group, the brain water content of butylphthalide group rats was induced (73.67 ± 0.67 vs 74.14 ± 0.46; 74.89 ± 0.57 vs 75.61 ± 0.52; 77.49 ± 0.34 vs 79.33 ± 0.49; 76.31 ± 0.56 vs 78.01 ± 0.48; 72.36 ± 0.44 vs 73.12 ± 0.73; P < 0.05), the permeability of blood–brain barrier of butylphthalide group rats was induced (319.20 ± 8.11 vs 394.60 ± 6.19; 210.40 ± 9.56 vs 266.40 ± 7.99; 188.00 ± 9.22 vs 232.40 ± 7.89; 288.40 ± 7.86 vs 336.00 ± 6.71; 166.60 ± 6.23 vs 213.60 ± 13.79; P < 0.05), and the Rho A protein of butylphthalide group rats was decreased (western blot result: 1.2230 ± 0.0254 vs 1.3970 ± 0.0276; 1.5985 ± 0.0206 vs 2.0368 ± 0.0179; 1.4229 ± 0.0167 vs 1.7930 ± 0.0158;1.3126 ± 0.0236 vs 1.5471 ± 0.0158; P < 0.05). The butylphthalide could reduce the brain edema, protect the blood–brain barrier, and decrease the expression of Rho A around the infarction.     

Neuroprotection of Up-Regulated Carbon Monoxide by Electrical Acupuncture on Perinatal Hypoxic–Ischemic Brain Damage in Rats

This study investigated the neuroprotection and potential mechanism of carbon monoxide (CO) against perinatal hypoxic–ischemic brain damage in rats by electrical acupuncture (EA). Animal behavior, morphological changes, cystathionine beta-synthase (CBS), hypoxia-inducible factor-1α (HIF-1α), and heme oxygenase-1 (HO-1) expression levels, and CO content in rat cortex cells were determined. Results demonstrated that EA treatment decreased the slope behavior and increased the overhang behavior of perinatal rats. The treatment also decreased the number of positive cells. The activator and inhibitor of CBS aggravated and remitted the hypoxic damage in cortex cells, respectively. EA treatment decreased CBS expression level and increased HO-1 and HIF-1α expression levels in perinatal rat cortex cells. Compared with the control groups, the CO content of cortex cells in the EA treatment group significantly increased (**p < 0.01). We hypothesized that EA treatment increases cortical CO content to protect against hypoxic damage via the hydrogen sulfide/CBS–CO/HO-1–HIF-1α system. This study provided a significant reference for EA therapy and cued a novel protective mechanism for cerebral palsy.     

Neurobehavioral Toxicity Induced by Carbendazim in Rats and the Role of iNOS,Cox-2, and NF-κB Signalling Pathway

Neurochemical Research - Carbendazim (CBZ) is one of the most common fungicides used to fight plant fungal diseases, otherwise, it leaves residue on fruits, vegetables, and soil that contaminate...     

Regulation of BCRP (ABCG2) and P-Glycoprotein (ABCB1) by Cytokines in a Model of the Human Blood–Brain Barrier

Brain capillary endothelial cells form the blood–brain barrier (BBB), a highly selective permeability membrane between the blood and the brain. Besides tight junctions that prevent small hydrophilic compounds from passive diffusion into the brain tissue, the endothelial cells express different families of drug efflux transport proteins that limit the amount of substances penetrating the brain. Two prominent efflux transporters are the breast cancer resistance protein and P-glycoprotein (P-gp). During inflammatory reactions, which can be associated with an altered BBB, pro-inflammatory cytokines are present in the systemic circulation. We, therefore, investigated the effect of the pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) on the expression and activity of BCRP and P-gp in the human hCMEC/D3 cell line. BCRP mRNA levels were significantly reduced by IL-1β, IL-6 and TNF-α. The strongest BCRP suppression at the protein level was observed after IL-1β treatment. IL-1β, IL-6 and TNF-α also significantly reduced the BCRP activity as assessed by mitoxantrone uptake experiments. P-gp mRNA levels were slightly reduced by IL-6, but significantly increased after TNF-α treatment. TNF-α also increased protein expression of P-gp but the uptake of the P-gp substrate rhodamine 123 was not affected by any of the cytokines. This in vitro study indicates that expression levels and activity of BCRP, and P-gp at the BBB may be altered by acute inflammation, possibly affecting the penetration of their substrates into the brain.