Number Of Glial Cells Research Articles

Long-Term Sequelae of Traumatic Brain Injury in Rats: A Morphological, Behavioral, and Electrophysiological Study

The long-term sequelae of traumatic brain injury (TBI) in humans are linked with the development of convulsions and cognitive and emotional disorders and are also associated with acceleration of brain aging processes and the formation of hippocampal sclerosis (HS). The mechanisms of these complications remain incompletely understood and treatment is extremely difficult. Existing data obtained using experimental models in animals do not provide a clear assessment of these mechanisms. The present study clarifies the long-term histological, behavioral, and electrophysiological sequelae of TBI in rats. Six months after lateral hydrodynamic blows, animals displayed severe asymmetrical gliosis in hippocampal field CA3 and the dental gyrus in the form of fibrillary astrogliosis, with an increase in the number of glial cells and depletion of the pyramidal layer of field CA3 in the ipsilateral hemisphere (corresponding to type 3 HS in humans); sham-operated animals displayed only symmetrical gliosis (isolated gliosis in the human HS classification). The behavior of the rats six months after TBI and the sham procedure was characterized by decreases in motor activity, which some signs of increased anxiety. Behavioral impairments were more severe in rats after TBI, mainly due to decreases in exploratory activity. The long-term period of TBI was characterized on ECoG by prolonged spike-wave discharges in the cortex and asymmetry of epileptiform spikes in the hippocampus. Two rats in the late period demonstrated epileptic seizures. Intense brain aging processes in rats with TBI and the development of neurodegenerative changes in the hippocampus may be linked with chronic remote neuroinflammation, which plays an important role in the development of posttraumatic epilepsy and dementia.

Morphological changes of the myenteric plexus at different gut segments of human fetuses

ABSTRACT The neural crest cell-derived enteric nervous system (ENS) is the intrinsic innervation of the gastrointestinal tract (GIT) which consists of neurons and enteric glia cells in the myenteric ganglia and forming plexus. The ENS consists mainly of submucosal and myenteric plexuses. It has various functions on the GIT, which include control of local blood flow, motility, mucosal transport, secretions, immune modulation as well as endocrine functions and coordinated contractile activity of smooth muscle. The knowledge on the development of the innervations at different segments of the gut in humans from 11 to 26 weeks of gestation (WG) may help in understanding the pathophysiology of various congenital diseases affecting the ENS. The aim of this study is to determine the morphology of the myenteric plexus in the esophagus, ascending colon and sigmoid colon at various weeks of gestation. Tissue samples from 10 naturally terminated fetuses aged 11–26 WG were processed for hematoxylin and eosin staining and immunohistochemistry assay. The neurons, enteric glia, the smooth muscle were visualized using PGP9.5, Vimentin and S-100 antibodies. The number of neurons and enteric glial cells appeared lowest in the esophagus than the ascending and sigmoid colon. The myenteric ganglion was closely apposed to each other, forming a continuous arch along the entire circumference of gut sections of ascending and sigmoid colon but the myenteric ganglia in the esophagus was thinly populated and widely spread in the fetus at 13 WG. As the fetal gastrointestinal tract grew in diameter and length, the myenteric ganglia became discernible.

Cell-Scale Modeling to Probe Mechanobiology during Early Cortical Development

Background/Objective: During early cerebral cortex development, neurons form from proliferative glial cells near the ventricular (apical) surface, then migrate along radial glial scaffolds to the cortical surface. In species with wrinkled brains, the presence of basal radial glial cells (bRGCs), radial glial cells which have detached from the ventricular surface, is correlated to the process of gyrification. While mechanical forces are also involved in gyrus creation, the link between the mechanical and biological aspects of this process remains unelucidated. In this study, we hypothesized that radial tension may lead to the production of gyri via the intermediary creation of bRGCs. 
 Methods: To test this hypothesis, the cell-level modeling software CX3D was used to simulate a system in which radial tension acts on radial glial cells (RGCs), facilitating the semi-stochastic production of bRGCs during the process of neocortex development. The outcome of this model was contrasted with a control case in which bRGCs were not allowed to form, and the two models were compared based upon the presence of neurons on the basal surface. 
 Results: The production of bRGCs via tension corresponded to a significant increase in the presence of neurons on the pial surface, even if the total number of glial cells—and thus total number of neurons generated—remained constant. Additionally, the likelihood of neurons moving more basally was found to be significantly greater in the presence of bRGCs. 
 Conclusion and Potential Impact: These results were interpreted to be indications of early gyrus formation. Thus, this study showed that bRGCs—and, ultimately, gyri—may arise from mechanical tension, indicating a possible link between the biological and mechanical explanations of gyrus formation. By providing an alternative lens through which to understand cortical folding, this may have implications for future lines of inquiry, which may expand our understanding of neuro-pathologies associated with misfolding, such as autism and epilepsy.

Neuroinflammation changes with periodontal inflammation status during periodontitis in wild‐type mice

To investigate neuroinflammation under different periodontal status. Experimental periodontitis was induced by molar ligation (Lig group) or periodontal injection of lipopolysaccharide (LPS, Lps group). Periodontal status was assessed by alveolar bone resorption and periodontal inflammation. Micro-computed tomography and haematoxylin-eosin staining were performed to assess alveolar bone resorption and periodontal inflammation, respectively. Neuroinflammation was assessed by glial cell proliferation and proinflammatory factor expression. Microgliosis was determined by immunofluorescence. Astrogliosis was determined by immunohistochemistry. Expressions of tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-1β were assessed by enzyme-linked immunosorbent assay. Microgliosis and astrogliosis in the Lig group were notable with molar ligation for 2weeks and 4weeks (p<.05), but were only slightly different similar from the control group by week 12. Microgliosis and astrogliosis in the Lps group were significant with LPS injection for 4 and 8weeks (p<.05). The groups displayed a positive correlation between the degree of periodontal inflammation and the number of glial cells (p<.05). Expressions of IL-1β and TNF-α in the Lps group were significantly increased with LPS injection for 8weeks (p<.05). In the Lig group, only TNF-α was highly expressed with molar ligation for 12weeks (p<.05). Both models demonstrated that the inflammatory response in the hippocampus of mice can change during periodontitis depending on the periodontal inflammation status.

Df(h15q13)/+ Mouse Model Reveals Loss of Astrocytes and Synaptic-Related Changes of the Excitatory and Inhibitory Circuits in the Medial Prefrontal Cortex.

The 15q13.3 deletion is associated with multiple neurodevelopmental disorders including epilepsy, schizophrenia, and autism. The Df(h15q13)/+ mouse model was recently generated that recapitulates several phenotypic features of the human 15q13.3 deletion syndrome (DS). However, the biological substrates underlying these phenotypes in Df(h15q13)/+ mice have not yet been fully characterized. RNA sequencing followed by real-time quantitative PCR, western blotting, liquid chromatography-mass spectrometry, and stereological analysis were employed to dissect the molecular, structural, and neurochemical phenotypes of the medial prefrontal cortex (mPFC) circuits in Df(h15q13)/+ mouse model. Transcriptomic profiling revealed enrichment for astrocyte-specific genes among differentially expressed genes, translated by a decrease in the number of glial fibrillary acidic protein positive cells in mPFC of Df(h15q13)/+ mice compared with wild-type mice. mPFC in Df(h15q13)/+ mice also showed a deficit of the inhibitory presynaptic marker GAD65, in addition to a reduction in dendritic arborization and spine density of pyramidal neurons from layers II/III. mPFC levels of GABA and glutamate neurotransmitters were not different between genotypes. Our results suggest that the 15q13.3 deletion modulates nonneuronal circuits in mPFC and confers molecular and morphometric alterations in the inhibitory and excitatory neurocircuits, respectively. These alterations potentially contribute to the phenotypes accompanied with the 15q13.3DS.

Is There a Correlation Between the Number of Brain Cells and IQ?

Our access to a unique material of postmortem brains obtained from decades of data collection enabled a stereological analysis of the neuron numbers and correlation of results with individual premorbid intelligence quotient (IQ) data. In our sample of 50 brains from men, we find that IQ does not correlate with the number of brain cells in the human neocortex and was only weakly correlated to brain weight. Our stereological examination extended to measures of several other parameters that might be of relevance to intelligence, including numbers of cerebral glial cells (astrocytes, oligodendrocytes, and microglia) and the volume of key areas in the gray and white matter and of the cerebral ventricles, also showing near-zero nonsignificant correlations to IQ.

Central cholinergic function and metabolic changes in streptozotocin-induced rat brain injury.

As glucose hypometabolism in the brain is an early sign of Alzheimer´s dementia (AD), the diabetogenic drug streptozotocin (STZ) has been used to induce Alzheimer-like pathology in rat brain by intracereboventricular injection (icv-STZ). However, many details of the pathological mechanism of STZ in this AD model remain unclear. Here, we report metabolic and cholinergic effects of icv-STZ using microdialysis in freely moving animals. We found that icv-STZ at a dose of 3mg/kg (2×1.5mg/kg) causes overt toxicity reflected in body weight loss. Three weeks after STZ administration, histological examination revealed a high number of glial fibrillary acidic protein reactive cells in the hippocampus, accompanied by Fluoro-Jade C-positive cells in the CA1 region. Glucose and lactate levels in microdialysates were unchanged, but mitochondrial respiration measured ex vivo was reduced by 9%-15%. High-affinity choline uptake, choline acetyltransferase, and acetylcholine esterase (AChE) activities in the hippocampus were reduced by 16%, 28%, and 30%, respectively. Importantly, extracellular acetylcholine (ACh) levels in the hippocampus were unchanged and responded to behavioral and pharmacological challenges. In comparison, extracellular ACh levels and cholinergic parameters in the striatum were unchanged or slightly increased. We conclude that the icv-STZ model poorly reflects central cholinergic dysfunction, an important characteristic of dementia. The icv-STZ model may be more aptly described as an animal model of hippocampal gliosis.

Luteolin Protects Against CIRI, Potentially via Regulation of the SIRT3/AMPK/mTOR Signaling Pathway.

Mitochondrial abnormalities accelerate the progression of ischemic brain damage. Sirtuin 3 (SIRT3) is mainly found in mitochondria and affects almost all major aspects of mitochondrial function. Luteolin, a flavonoid with diverse biological properties, including antioxidant activity, inhibition of cell apoptosis and regulation of autophagy. It also modulates the activity of AMP activated kinase and/or sirtuin 1 (SIRT 1) by regulating the expression of sirtuins. We investigated the protective effects of luteolin on cerebral ischemia-reperfusion. It was found through experiments that luteolin reduced the infarcted area of MCAO rat model, and based on the experimental results, it was inferred that luteolin affected the AMPK, mTOR and SIRT3 pathways, thereby protecting brain cells. As expected, we found that luteolin can reduce the neurological function score, the degree of cerebral edema, the cerebral infarction volume, alleviate morphological changes in the cortex and hippocampus, increase neuron survival and decrease the number of apoptotic neurons. At the same time, luteolin significantly reduced the number of GFAP and Iba-1 positive glial cells in the hippocampus while enhanced the scavenging of oxygen free radicals and the activity of SOD in mitochondria. Addtionally, it can also enhance antioxidant capacity via the reversal of mitochondrial swelling and the mitochondrial transmembrane potential. Moreover, luteolin can increase SIRT3-targeted expression in mitochondria, decrease the phosphorylation of AMPK, and increase phosphor-mTOR (p-mTOR) levels, which may have occurred specifically through activation of the SIRT3/AMPK/mTOR pathway. We speculate that luteolin reduces the pathological progression of CIRI by increasing SIRT3 expression and enhancing mitochondrial function. Therefore, the results indicate that luteolin can increase the transduction of SIRT3, providing a potential mechanism for neuroprotective effects in patients with cerebral ischemia.

Curcumin prevents neuronal loss and structural changes in the superior cervical (sympathetic) ganglion induced by chronic sleep deprivation, in the rat model

BackgroundIn modern societies, sleep deprivation is a serious health problem. This problem could be induced by a variety of reasons, including lifestyle habits or neurological disorders. Chronic sleep deprivation (CSD) could have complex biological consequences, such as changes in neural autonomic control, increased oxidative stress, and inflammatory responses. The superior cervical ganglion (SCG) is an important sympathetic component of the autonomic nervous system. CSD can lead to a wide range of neurological consequences in SCG, which mainly supply innervations to circadian system and other structures. As the active component of Curcuma longa, curcumin possesses many therapeutic properties; including neuroprotective. This study aimed to evaluate the effect of CSD on the SCG histomorphometrical changes and the protective effect of curcumin in preventing these changes.MethodsThirty-six male rats were randomly assigned to the control, curcumin, CSD, CSD + curcumin, grid floor control, and grid floor + curcumin groups. The CSD was induced by a modified multiple platform apparatus for 21 days and animals were sacrificed at the end of CSD or treatment, and their SCGs removed for stereological and TUNEL evaluations and also spatial arrangement of neurons in this structure.ResultsConcerning stereological findings, CSD significantly reduced the volume of SCG and its total number of neurons and satellite glial cells in comparison with the control animals (P < 0.05). Treatment of CSD with curcumin prevented these decreases. Furthermore, TUNEL evaluation showed significant apoptosis in the SCG cells in the CSD group, and treatment with curcumin significantly decreased this apoptosis (P < 0.01). This decrease in apoptosis was observed in all control groups that received curcumin. CSD also changed the spatial arrangement of ganglionic neurons into a random pattern, whereas treatment with curcumin preserved its regular pattern.ConclusionsCSD could potentially induce neuronal loss and structural changes including random spatial distribution in the SCG neurons. Deleterious effects of sleep deprivation could be prevented by the oral administration of curcumin. Furthermore, the consumption of curcumin in a healthy person might lead to a reduction of cell death.

Ketogenic Diet Provided During Three Months Increases KCC2 Expression but Not NKCC1 in the Rat Dentate Gyrus.

Ketogenic diet, a high fat and low carbohydrate diet, has been used as a non-pharmacological treatment in refractory epilepsy since 1920. In recent years, it has demonstrated to be effective in the treatment of numerous neurological and non-neurological diseases. Some neurological and neuropsychiatric disorders are known to be caused by gamma-aminobutyric acid (GABA)-mediated neurotransmission dysfunction. The strength and polarity of GABA-mediated neurotransmission are determined by the intracellular chloride concentration, which in turn is regulated by cation-chloride cotransporters NKCC1 and KCC2. Currently, it is unknown if the effect of ketogenic diet is due to the modulation of these cotransporters. Thus, we analyzed the effect of a ketogenic diet on the cation-chloride cotransporters expression in the dentate gyrus. We estimated the total number of NKCC1 immunoreactive (NKCC1-IR) neuronal and glial cells by stereology and determined KCC2 labeling intensity by densitometry in the molecular and granule layers as well as in the hilus of dentate gyrus of rats fed with normal or ketogenic diet for 3 months. The results indicated that ketogenic diet provided during 3 months increased KCC2 expression, but not NKCC1 in the dentate gyrus of the rat. The significant increase of KCC2 expression could explain, at least in part, the beneficial effect of ketogenic diet in the diseases where the GABAergic system is altered by increasing its inhibitory efficiency.

Maternal Hyperhomocysteinemia Induces Neuroinflammation and Neuronal Death in the Rat Offspring Cortex.

Maternal hyperhomocysteinemia is one of the common complications of pregnancy that causes offspring cognitive deficits during postnatal development. In the present work, we evaluated the effect of prenatal hyperhomocysteinemia on structural and ultrastructural organization, neuronal and glial cell number, apoptosis (caspase-3 content and activity), inflammatory markers (tumor necrosis factor-α, interleukin-6, and interleukin-1β), and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation in the offspring brain cortex in early ontogenesis. Wistar female rats received methionine (0.6g/kg body weight) by oral administration during pregnancy. Histological and biochemical analyses of 5- and 20-day-old pups' cortical tissue were performed. Lysosome accumulation and other neurodegenerative changes in neurons of animals with impaired embryonic development were investigated by electron microscopy. Neuronal staining (anti-NeuN) revealed a reduction in neuronal number, accompanied by increasing of caspase-3 active form protein level and activity. Maternal hyperhomocysteinemia also elevated the number of astroglial and microglial cells and increased expression of interleukin-1β and p38 MAPK phosphorylation, which indicates the development of neuroinflammatory processes.

Therapeutic effect of erythropoietin on brain injury in premature mice with intrauterine infection.

ObjectiveThe objective of this study is to explore the protective effect of erythropoietin (EPO) on brain injury induced by intrauterine infection in premature infants and its related mechanism, so as to provide reference for clinical medication.MethodsIntrauterine infection model is established by injecting lipopolysaccharide into pregnant mice, and HE staining of mouse placenta is used to judge whether the model of intrauterine infection is successful or not. Fifteen female rats are successfully pregnant and divided into intrauterine infection group (10 rats) and control group (5 rats). The mice in the intrauterine infection group are intraperitoneally injected with lipopolysaccharide (LPS) at a dose of 0.3 mg/kg. After delivery, 16 newborn mice in the control group are randomly selected as blank control group. 32 newborn mice in the intrauterine infection group are selected as model group, and then divided into infection group and EPO treatment group, 16 mice in each group. After birth, mice in the blank control group are intraperitoneally injected with 0.2 mL saline daily. The infected mice are intraperitoneally injected with 0.2 mL saline daily. The mice in the EPO treatment group are intraperitoneally injected with recombinant human erythropoietin (rhEPO) 5000 IU/kg daily. HE staining results, EPOR protein and NMDAR1 mRNA expression in brain tissue of three groups of neonatal mice were compared.ResultsFirstly, the blood vessels of the mice in the intrauterine infection group are markedly hyperemic and edematous, and the infiltration of neutrophils is increased. The white matter structure of the neonatal mice in the intrauterine infection group is loose and stained lightly. The nerve fibers in the brain are different in thickness and disordered in arrangement. The nucleus is small and dark stained. The number of glial cells in brain tissue increases significantly. Secondly, the EPOR protein expression and physiological level of neonatal mice in intrauterine infection group increase significantly at 3, 7 and 14 days after birth. Compared with the blank control group, the difference is statistically significant (P < 0.05). On the 3rd day after birth, the expression level of EPOR protein in the EPO treated group is significantly higher than that in the intrauterine infection group (P < 0.05). Thirdly, the expression level of NMDA R1mRNA in brain tissue of neonatal mice at birth, on the 3rd and 7th day after EPO treatment is significantly lower than that of intrauterine infection group (P < 0.05).ConclusionEPO can promote the proliferation and differentiation of brain endogenous neural stem cells, and has a certain therapeutic effect on brain injury of premature mice caused by intrauterine infection.

TDAG8 deficiency reduces satellite glial number and pro-inflammatory macrophage number to relieve rheumatoid arthritis disease severity and chronic pain

BackgroundThe autoimmune disease rheumatoid arthritis (RA) affects approximately 1% of the global population. RA is characterized with chronic joint inflammation and often associated with chronic pain. The imbalance of pro-inflammatory and anti-inflammatory macrophages is a feature of RA progression. Glial cells affecting neuronal sensitivity at both peripheral and central levels may also be important for RA progression and associated pain. Genetic variants in the T cell death-associated gene 8 (TDAG8) locus are found to associate with spondyloarthritis. TDAG8 was also found involved in RA disease progression and associated hyperalgesia in the RA mouse model. However, its modulation in RA remains unclear.MethodsTo address this question, we intra-articularly injected complete Freund’s adjuvant (CFA) into TDAG8+/+, TDAG8−/− or wild-type mice, followed by pain behavioral tests. Joints and dorsal root ganglia were taken, sectioned, and stained with antibodies to observe the number of immune cells, macrophages, and satellite glial cells (SGCs). For compound treatments, compounds were intraperitoneally or orally administered weekly for 9 consecutive weeks after CFA injection.ResultsWe demonstrated that TDAG8 deletion slightly reduced RA pain in the early phase but dramatically attenuated RA progression and pain in the chronic phase (> 7 weeks). TDAG8 deletion inhibited an increase in SGC number and inhibition of SGC function attenuated chronic phase of RA pain, so TDAG8 could regulate SGC number to control chronic pain. TDAG8 deletion also reduced M1 pro-inflammatory macrophage number at 12 weeks, contributing to the attenuation of chronic RA pain. Such results were further confirmed by using salicylanilide derivatives, CCL-2d or LCC-09, to suppress TDAG8 expression and function.ConclusionsThis study demonstrates that TDAG8 deletion reduced SGC and M1 macrophage number to relieve RA disease severity and associated chronic pain. M1 macrophages are critical for the development and maintenance of RA disease and pain, but glial activation is also required for the chronic phase of RA pain.

Short-Term Environmental Enrichment is a Stronger Modulator of Brain Glial Cells and Cervical Lymph Node T Cell Subtypes than Exercise or Combined Exercise and Enrichment

Physical exercise (PE) and environmental enrichment (EE) can modulate immunity. However, the differential effects of short-term PE, EE, and PE + EE on neuroimmune mechanisms during normal aging has not been elucidated. Hence, a cohort of 3-, 8-, and 13-month-old immunologically unchallenged C57BL/6 wild-type mice were randomly assigned to either Control, PE, EE, or PE + EE groups and provided with either no treatment, a running wheel, a variety of plastic and wooden objects alone or in combination with a running wheel for seven weeks, respectively. Immunohistochemistry and 8-color flow cytometry were used to determine the numbers of dentate gyrus glial cells, and the proportions of CD4+ and CD8+ T cell numbers and their subsets from cervical lymph nodes, respectively. An increase in the number of IBA1+ microglia in the dentate gyrus at 5 and 10 months was observed after EE, while PE and PE + EE increased it only at 10 months. No change in astroglia number in comparison to controls were observed in any of the treatment groups. Also, all treatments induced significant differences in the proportion of specific T cell subsets, i.e., CD4+ and CD8+ T naïve (TN), central memory (TCM), and effector memory (TEM) cells. Our results suggest that in the short-term, EE is a stronger modulator of microglial and peripheral T cell subset numbers than PE and PE + EE, and the combination of short-term PE and EE has no additive effects.

Embryonic microglia influence developing hypothalamic glial populations

BackgroundAlthough historically microglia were thought to be immature in the fetal brain, evidence of purposeful interactions between these immune cells and nearby neural progenitors is becoming established. Here, we examined the influence of embryonic microglia on gliogenesis within the developing tuberal hypothalamus, a region later important for energy balance, reproduction, and thermoregulation.MethodsWe used immunohistochemistry to quantify the location and numbers of glial cells in the embryonic brain (E13.5–E17.5), as well as a pharmacological approach (i.e., PLX5622) to knock down fetal microglia. We also conducted cytokine and chemokine analyses on embryonic brains in the presence or absence of microglia, and a neurosphere assay to test the effects of the altered cytokines on hypothalamic progenitor behaviors.ResultsWe identified a subpopulation of activated microglia that congregated adjacent to the third ventricle alongside embryonic Olig2+ neural progenitor cells (NPCs) that are destined to give rise to oligodendrocyte and astrocyte populations. In the absence of microglia, we observed an increase in Olig2+ glial progenitor cells that remained at the ventricle by E17.5 and a concomitant decrease of these Olig2+ cells in the mantle zone, indicative of a delay in migration of these precursor cells. A further examination of maturing oligodendrocytes in the hypothalamic grey and white matter area in the absence of microglia revealed migrating oligodendrocyte progenitor cells (OPCs) within the grey matter at E17.5, a time point when OPCs begin to slow their migration. Finally, quantification of cytokine and chemokine signaling in ex vivo E15.5 hypothalamic cultures +/− microglia revealed decreases in the protein levels of several cytokines in the absence of microglia. We assayed the influence of two downregulated cytokines (CCL2 and CXCL10) on neurosphere-forming capacity and lineage commitment of hypothalamic NPCs in culture and showed an increase in NPC proliferation as well as neuronal and oligodendrocyte differentiation.ConclusionThese data demonstrate that microglia influence gliogenesis in the developing tuberal hypothalamus.

Duration of Environmental Enrichment Determines Astrocyte Number and Cervical Lymph Node T Lymphocyte Proportions but Not the Microglial Number in Middle-Aged C57BL/6 Mice.

Environmental enrichment (EE) has been shown to modulate behavior and immunity. We recently reported that both short and long-term EE enhance baseline locomotion and alleviate depressive-like behavior, but only long-term EE affects locomotion adversely in a threatening environment and enhances anxiety-like behavior in middle-age mice. We have now investigated whether the observed changes in behavior after short- and long-term EE were associated with underlying immune changes. Hence, at the end of behavioral testing, mice were sacrificed, and brains and cervical lymph nodes were collected to investigate the differential effects of the duration of EE (short- and long-term) on the number of immunopositive glial cells in the dentate gyrus, CA1, CA2, and CA3 regions of the hippocampus and proportions of T cell subsets in the cervical lymph nodes using immunohistochemistry and flow cytometry, respectively. EE, regardless of duration, caused an increase in microglia number within the dentate gyrus, CA1 and CA3 hippocampal regions, but only long-term EE increased astrocytes number within the dentate gyrus and CA3 hippocampal regions. A significantly higher proportion of CD8+ naive T cells was observed after long-term EE vs. short-term EE. No significant differences were observed in the proportion of central memory and effector memory T cells or early activated CD25+ cells between any of the test groups. Our results suggest that EE, irrespective of duration, enhances the numbers of microglia, but long-term EE is required to modify astrocyte number and peripheral T cell proportions in middle-aged mice. Our findings provide new insights into the therapeutic effects of EE on various brain disorders, which may be at least partly mediated by glial and neuroimmune modulation.

Elevated serum chemokine CCL22 levels in first-episode psychosis: associations with symptoms, peripheral immune state and in vivo brain glial cell function

Several lines of research support immune system dysregulation in psychotic disorders. However, it remains unclear whether the immunological marker alterations are stable and how they associate with brain glial cell function. This longitudinal study aimed at investigating whether peripheral immune functions are altered in the early phases of psychotic disorders, whether the changes are associated with core symptoms, remission, brain glial cell function, and whether they persist in a one-year follow-up. Two independent cohorts comprising in total of 129 first-episode psychosis (FEP) patients and 130 controls were assessed at baseline and at the one-year follow-up. Serum cyto-/chemokines were measured using a 38-plex Luminex assay. The FEP patients showed a marked increase in chemokine CCL22 levels both at baseline (p < 0.0001; Cohen’s d = 0.70) and at the 12-month follow-up (p = 0.0007) compared to controls. The group difference remained significant (p = 0.0019) after accounting for relevant covariates including BMI, smoking, and antipsychotic medication. Elevated serum CCL22 levels were significantly associated with hallucinations (ρ = 0.20) and disorganization (ρ = 0.23), and with worse verbal performance (ρ = −0.23). Brain glial cell activity was indexed with positron emission tomography and the translocator protein radiotracer [11C]PBR28 in subgroups of 15 healthy controls and 14 FEP patients with serum CCL22/CCL17 measurements. The distribution volume (VT) of [11C]PBR28 was lower in patients compared to controls (p = 0.026; Cohen’s d = 0.94) without regionally specific effects, and was inversely associated with serum CCL22 and CCL17 levels (p = 0.036). Our results do not support the over-active microglia hypothesis of psychosis, but indicate altered CCR4 immune signaling in early psychosis with behavioral correlates possibly mediated through cross-talk between chemokine networks and dysfunctional or a decreased number of glial cells.

The Effects of Newcastle virus Histologically Suspension on Some Organs of White Mice (Balb /c)

Newcastle disease is a contagious bird disease affecting wild avian species and many domestic,it may be transmissible to humans. Detection of Newcasstle virus confirmed by rapid test technique(Immunochromatography) . ten sample (10% ) out of 100 fasces sample collected from chickens were posative. Twelve mice used in this study devided into two groups ,first group consist of six mice induced with 0.2 ml from one positive sample of Newcasttle virus suspension to evaluate some histopathological changes caused by Newcasstle virus in small intestine and stomach of mice,second group induced with 0.2 ml from phosphate buffer saline only. The results revealed that histopathological changes in liver induced by using 0.2 ml from the positive Newcasstle virus suspension as hyperpalsia in kufper cells. Lung of mice treated with this concentration of Newcasstle virus has partial pnemonia and thicking the intra alveolar walls. While brain of mice treated with same concentration suffering from increase in number of glial cells ( glialosis ) and apoptosis in brain cells.

Untreated Patients Dying With AIDS Have Loss of Neocortical Neurons and Glia Cells.

Untreated human immunodeficiency virus (HIV) depletes its host CD4 cells, ultimately leading to acquired immunodeficiency syndrome (AIDS). In brain, the HIV confines itself to astrocytes and microglia, the resident brain macrophages, but does not infect oligodendrocytes and neurons. Nonetheless, cognitive symptoms associated with HIV and AIDS are attributed to loss of axons and white matter damage. We used design-based stereology to estimate the numbers of neocortical neurons and glial cells (astrocytes, oligodendrocytes, and microglia), in a series of 12 patients dying with AIDS before the era of retroviral treatments, and in 13 age-matched control brains. Relative to the control material, there was a 19% loss of neocortical neuron (p = 0.04) and a 29% reduction of oligodendrocytes (p = 0.003) in the patients with AIDS, whereas astrocyte and microglia numbers did not differ between patients and controls. Furthermore, we saw a 17% reduction in mean hemispheric volume in the AIDS group (p = 0.0015), which was driven by neocortical and white matter loss (p < 0.05), while the archicortex, subcortical gray matter, and ventricular volumes were within normal limits. Our results confirm previous reports of neuronal loss in AIDS. The new finding of oligodendrocyte loss supports the proposal that HIV in the brain provokes demyelination and axonal dysfunction and suggests that remyelination treatment strategies may be beneficial to patients suffering from HIV-associated neurocognitive deficits.

Dangerous Liaison: Helicobacter pylori, Ganglionitis, and Myenteric Gastric Neurons: A Histopathological Study.

Chronic inflammation induced by Helicobacter pylori (H. pylori) infection plays a major role in development of gastric cancer. However, recent findings suggested that progression of inflammation and neoplastic transformation in H. pylori infection are more complex than previously believed and could involve different factors that modulate gastric microenvironment and influence host-pathogen interaction. Among these factors, gastric myenteric plexus and its potential adaptive changes in H. pylori infection received little attention. This study is aimed at identifying the impact of H. pylori-associated gastritis on number and morphology of nerve cells in the stomach. The distribution of density, inflammation, and programmed cell death in neurons was immunohistochemically assessed in full-thickness archival tissue samples obtained from 40 patients with H. pylori infection who underwent surgery for gastric cancer and were compared with findings on samples collected from 40 age- and sex-matched subjects without bacteria. Overall, significant differences were noted between H. pylori-positive and H. pylori-negative patients. The analysis of tissue specimens obtained from those with infection revealed higher density and larger surface of the myenteric nervous plexus, as well as a significant increase in the number of gastric neuronal cell bodies and glial cells compared to controls. A predominant CD3-immunoreactive T cell infiltrate confined to the myenteric plexus was observed in infected subjects. The presence of mature B lymphocytes, plasma cells, and eosinophils was also noted, but to a lesser extent, within the ganglia. Myenteric ganglionitis was associated with degeneration and neuronal loss. Our results represent the first histopathological evidence supporting the hypothesis that H. pylori-induced gastric inflammation may induce morphological changes in myenteric gastric ganglia. These findings could help gain understanding of some still unclear aspects of pathogenesis of H. pylori infection, with the possibility of having broader implications for gastric cancer progression.