Abnormal myelination underlies the pathology of white matter diseases such as preterm white matter injury and multiple sclerosis. Osteopontin (OPN) has been suggested to play a role in myelination. Murine OPN mRNA is translated into a... more
Abnormal myelination underlies the pathology of white matter diseases such as preterm white matter injury and multiple sclerosis. Osteopontin (OPN) has been suggested to play a role in myelination. Murine OPN mRNA is translated into a secreted isoform (sOPN) or an intracellular isoform (iOPN). Whether there is an isoform‐specific involvement of OPN in myelination is unknown. Here we generated mouse models that either lacked both OPN isoforms in all cells (OPN‐KO) or lacked sOPN systemically but expressed iOPN specifically in oligodendrocytes (OLs‐iOPN‐KI). Transcriptome analysis of isolated oligodendrocytes from the neonatal brain showed that genes and pathways related to increase of myelination and altered cell cycle control were enriched in the absence of the two OPN isoforms in OPN‐KO mice compared to control mice. Accordingly, adult OPN‐KO mice showed an increased axonal myelination, as revealed by transmission electron microscopy imaging, and increased expression of myelin‐related proteins. In contrast, neonatal oligodendrocytes from OLs‐iOPN‐KI mice compared to control mice showed differential regulation of genes and pathways related to the increase of cell adhesion, motility, and vasculature development, and the decrease of axonal/neuronal development. OLs‐iOPN‐KI mice showed abnormal myelin formation in the early phase of myelination in young mice and signs of axonal degeneration in adulthood. These results suggest an OPN isoform‐specific involvement, and a possible interplay between the isoforms, in myelination, and axonal integrity. Thus, the two isoforms of OPN need to be separately considered in therapeutic strategies targeting OPN in white matter injury and diseases.
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Staphylococcus epidermidis (S. epidermidis) is the most common nosocomial pathogen in preterm infants and associated with increased risk of cognitive delay, however, underlying mechanisms are unknown. We employed morphological,... more
Staphylococcus epidermidis (S. epidermidis) is the most common nosocomial pathogen in preterm infants and associated with increased risk of cognitive delay, however, underlying mechanisms are unknown. We employed morphological, transcriptomic and physiological methods to extensively characterize microglia in the immature hippocampus following S. epidermidis infection. 3D morphological analysis revealed activation of microglia after S. epidermidis. Differential expression combined with network analysis identified NOD‐receptor signaling and trans‐endothelial leukocyte trafficking as major mechanisms in microglia. In support, active caspase‐1 was increased in the hippocampus and using the LysM‐eGFP knock‐in transgenic mouse, we demonstrate infiltration of leukocytes to the brain together with disruption of the blood–brain barrier. Our findings identify activation of microglia inflammasome as a major mechanism underlying neuroinflammation following infection. The results demonstrate that neonatal S. epidermidis infection share analogies with S. aureus and neurological diseases, suggesting a previously unrecognized important role in neurodevelopmental disorders in preterm born children.
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Galactomannan (GM) antigen is an aspergillus specific antigen that is released during the growth phase of invasive aspergillosis. We aimed to find the optimum cutoff and accuracy of serum Galactomannan assay in immunocompromised patients.... more
Galactomannan (GM) antigen is an aspergillus specific antigen that is released during the growth phase of invasive aspergillosis. We aimed to find the optimum cutoff and accuracy of serum Galactomannan assay in immunocompromised patients. Immunocompromised patients diagnosed with invasive pulmonary aspergillosis (IPA) based on the European Organization for Research and Treatment of Cancer/Invasive Mycosis Study Group (EORTC/MSG) with three levels of certainty proven, probable and possible, referred for GM antigen measurement at Immunology, Asthma and Allergy Research Institute (IAARI) from 2006 to 2009 and if they met the criteria were enrolled in this study. Totally 49 patients with IPA were enrolled in our study. According to EORTC/MSG, patients categorized into three levels of certainty: They were diagnosed as 'proven' invasive pulmonary aspergillosis 16(32.7%), 'probable' 18(36.7%) and 'possible' 15(30.6%). The most common host risk factor was solid tumors 17(34.7%). The accuracy of Galactomannan assay increased from 0.5 to 2 cutoffs. The optimum sensitivity and specificity obtained at the index cutoff of ≥1.5 for diagnosis of "proven" IPA; which were respectively, 69.2% and 72.2%. Other cutoffs had high variance between sensitivity and specificity for diagnosis of IPA. The calculated cutoff gained by receiver operating characteristic (ROC) analysis for detecting proven IPA was 1.5. Intermediate accuracy of serum GM test in conjunct with clinical findings would help early IPA detection among immunocompromised patients.
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Autism Spectrum Disorders (ASD) are heterogeneous neurodevelopmental disorders with considerably increased risk in male infants born preterm and with neonatal infection. Here we investigated the role of postnatal immune activation on... more
Autism Spectrum Disorders (ASD) are heterogeneous neurodevelopmental disorders with considerably increased risk in male infants born preterm and with neonatal infection. Here we investigated the role of postnatal immune activation on hippocampal synaptopathology by targeting Reelin+ cells in mice with ASD-like behavior. C57/Bl6 mouse pups of both sexes received lipopolysaccharide (LPS, 1mg/kg) on postnatal day (P) 5. At P45, animal behavior was examined by marble burying and sociability test, followed by ex-vivo brain MRI diffusion kurtosis imaging (DKI). Hippocampal synaptogenesis, number and morphology of Reelin+ cells, and mRNA expression of trans-synaptic genes, including neurexin-3, neuroligin-1, and cell-adhesion molecule nectin-1 were analyzed at P12 and P45. Social withdrawal and increased stereotypic activities in males were related to increased mean diffusivity on MRI-DKI and overgrowth in hippocampus together with retention of long-thin immature synapses on apical dendrites, decreased volume and number of Reelin+ cells as well as reduced expression of trans-synaptic and cell-adhesion molecules. The study provides new insights into sex-dependent mechanisms that may underlie ASD-like behavior in males following PIA. We identify GABAergic interneurons as core components of dysmaturation of excitatory synapses in the hippocampus following postnatal infection and provide cellular and molecular substrates for the MRI findings with translational value.
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The purpose of this study was to investigate any association between IgA deficiency (IgAD) and juvenile rheumatoid arthritis (JRA) among Iranian children.This case-control study was carried out on 83 children who were diagnosed as JRA... more
The purpose of this study was to investigate any association between IgA deficiency (IgAD) and juvenile rheumatoid arthritis (JRA) among Iranian children.This case-control study was carried out on 83 children who were diagnosed as JRA according to American College of Rheumatology (ACR) criteria; Patients were admitted at the rheumatology clinic of Children's Medical Center, (Tehran). Serum immunoglobulins concentrations were determined by nephelometry method. Control group was 112 healthy children who were matched for age and gender. Informed consent obtained from all parents.Selective IgA deficiency (sIgAD) was found only in a boy (1.2%) among JRA children; however, partial IgA deficiency was found in 6(7.1%) of patients with JRA and in 12(10.7%) of control subjects, this difference was not statistically significant (p=0.46). Immunoglobulins levels in patients with JRA (IgM: 126.7±57.2, IgG: 1182.3±351 and IgA:169.3±98) were significantly higher than their controls (IgM: 104±52, IgG:802±220 and IgA: 94.6±47) (p<0.05). Patients with growth failure had higher IgM, IgG and IgA levels in comparison with patients without growth failure; however, this difference was significant about IgM and IgG levels (p<0.05).In contrast to other similar studies, the number of IgAD did not differ significantly between JRA patients and their control counterpart; this might be partly due to the high rate of consanguineous marriages in Iran that resulted in increased prevalence of clinically undiagnosed partial IgAD in general population. Hence, future epidemiological studies are warranted to make it clear.
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Schizophrenia (SCZ) is a psychiatric disorder that can include symptoms of disorganized speech and thoughts with uncertain underlying mechanisms possibly linked to over‐activated microglia. In this study, we used brain samples from... more
Schizophrenia (SCZ) is a psychiatric disorder that can include symptoms of disorganized speech and thoughts with uncertain underlying mechanisms possibly linked to over‐activated microglia. In this study, we used brain samples from sixteen donors with SCZ and thirteen control donors to assess the differential activation of microglia by quantifying density and 3D reconstruction of microglia stained with ionized calcium‐binding adaptor molecule‐1 (Iba1). Our samples consisted of sections from the frontal, temporal, and cingulate cortical gray matter, subcortical white matter regions (SCWM), and included the anterior corpus callosum. In the first series of studies, we performed a density analysis followed by a spatial analysis to ascertain the microglial density, distribution, and soma size in SCZ brains. Second, we performed a series of morphological quantification techniques to investigate the arborization patterns of the microglia in SCZ. The results demonstrated an increase in microglia density in the cortical gray matter regions in SCZ cases, while in the SCWM, there was a significant increase in microglia density in the frontal and temporal, but not in the other brain regions of interest (ROIs). Spatial analysis using the “nearest neighbor” demonstrated that there was no effect in “clustering”, but there were shorter distances between microglia seen in the SCZ cases. The morphological measures showed that there was a region‐dependent increase in the microglia soma size in the SCZ cases while the Sholl analysis revealed a significant decrease in the microglia arborization in the SCZ cases across all the ROI’s studied. An in‐depth 3D reconstruction of microglia in Brodmann area 9 cortical region found that there was a significant association between age and reduced microglial arborization in the SCZ cases. This region‐dependent age association can help determine whether longitudinal changes in microglial activation across age are brain region‐dependent, which may point to potential therapeutic targets.
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Transient cerebral ischemia followed by reperfusion in an infarcted brain comes with predictable acute and chronic morphological alterations in neuronal and non-neuronal cells. An accurate delineation of the cerebral infarct is not a... more
Transient cerebral ischemia followed by reperfusion in an infarcted brain comes with predictable acute and chronic morphological alterations in neuronal and non-neuronal cells. An accurate delineation of the cerebral infarct is not a simple task due to the complex shapes and indistinct borders of the infarction. Thus, an exact macroscopic histological approach for infarct volume estimation can lead to faster and more reliable preclinical research results. This study investigated the effect(s) of confounding factors such as fixation and tissue embedding on the quality of macroscopic visualization of focal cerebral ischemia by anti-microtubule-associated-protein-2 antibody (MAP2) with conventional Hematoxylin and Eosin (HE) staining serving as the control. The aim was to specify the most reliable macroscopic infarct size estimation method after sub-acute focal cerebral ischemia based on the qualitative investigation. Our results showed that the ischemic area on the MAP2-stained sections could be identified macroscopically on both cryo-preserved and paraffin-embedded sections from both immersion- and perfusion-fixed brains. The HE staining did not clearly depict an infarct area for macroscopic visualization. Therefore both immersion-fixed and perfused-fixed-MAP2 stained sections can be used reliably to quantify cerebral infarcts.
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Research Interests: Physiology, Biology, Medicine, Stereology, Somatostatin, and 7 morePreterm, GABA, Medical Physiology, Subiculum, White matter, Fetus, and Interneurons
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Neurological disorders (which include a broad spectrum of central nervous system diseases from children to old people) remain among the most compelling illnesses known to humankind [...]
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Neuroblastoma-like schwannoma is known as a rare unusual variant of schwannoma with difficulties of differential diagnosis with neuroblastoma, Ewing sarcoma/peripheral neuroectodermal tumor and other cutaneous small round cell tumors.... more
Neuroblastoma-like schwannoma is known as a rare unusual variant of schwannoma with difficulties of differential diagnosis with neuroblastoma, Ewing sarcoma/peripheral neuroectodermal tumor and other cutaneous small round cell tumors. Herein, we describe a neuroblastoma-like schwannoma that was presented as a painless lesion on the dorsal side of the left hand in a 39-year-old woman. Composed collagen fibers in the central core of rosettes and diffuse expression of S100 protein in the tumor cells found in the biopsy specimens confirmed the Schwann cell origin of the tumor.
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Inflammation plays a central role in the development of neonatal brain injury. The alpha 7 nicotinic acetylcholine receptor (α7nAChR) can modulate inflammation and has shown promising results as a treatment target in rodent models of... more
Inflammation plays a central role in the development of neonatal brain injury. The alpha 7 nicotinic acetylcholine receptor (α7nAChR) can modulate inflammation and has shown promising results as a treatment target in rodent models of adult brain injury. However, little is known about the role of the α7nAChR in neonatal brain injury. Hypoxic-ischemic (HI) brain injury was induced in male and female C57BL/6 mice, α7nAChR knock-out (KO) mice and their littermate controls on postnatal day (PND) 9–10. C57BL/6 pups received i.p. injections of α7nAChR agonist PHA 568487 (8 mg/kg) or saline once daily, with the first dose given directly after HI. Caspase-3 activity and cytokine mRNA expression in the brain was analyzed 24 h after HI. Motor function was assessed 24 and 48 h after HI, and immunohistochemistry was used to assess tissue loss at 24 h and 7 days after HI and microglial activation 7 days after HI. Activation of α7nAChR with the agonist PHA 568487 significantly decreased CCL2/MCP-1...
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The importance of statistics in biological research is inevitable. The appliance of statistics is the most powerful tool to support the scientific hypothesis and to give credibility to biological research methodology, to interpret... more
The importance of statistics in biological research is inevitable. The appliance of statistics is the most powerful tool to support the scientific hypothesis and to give credibility to biological research methodology, to interpret convoluted explanations and conclusions based on the research findings. The evidences from literatures point the persistent statistical errors, selection of non-proper statistical test with the consequence of misinterpretation of the scientific results which are published in international journals. One of the most extensively used statistical tests in the field of biology (preclinical and clinical) is analysis of variance (ANOVA). ANOVA test is in place of multiple T-tests to compare the means of more than two groups at a time; and there are some important points which biologists should be aware of them to avoid possible misinterpretation of results with the consequence of wrong conclusion. Accordingly, the aim of the current review is to help biologists t...
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Staphylococcus epidermidis(S. epidermidis) is the most common nosocomial pathogen in preterm infants and associated with increased risk of cognitive delay, however, underlying mechanisms are unknown. We employed morphological,... more
Staphylococcus epidermidis(S. epidermidis) is the most common nosocomial pathogen in preterm infants and associated with increased risk of cognitive delay, however, underlying mechanisms are unknown. We employed morphological, transcriptomic and physiological methods to extensively characterize microglia in the immature hippocampus followingS. epidermidisinfection. 3D morphological analysis revealed activation of microglia afterS. epidermidis. Differential expression combined with network analysis identified NOD-receptor signalling and trans-endothelial leukocyte trafficking as major mechanisms in microglia. In support, active caspase-1 was increased in the hippocampus and using the LysM-eGFP knock-in transgenic mouse, we demonstrate infiltration of leukocytes to the brain together with disruption of the blood-brain barrier. Our findings identify activation of microglia inflammasome as a major mechanism underlying neuroinflammation following infection. The results demonstrate that n...
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The neuro-gliovascular unit is a crucial structure for providing a balanced well-functioning environment for neurons and their synapses. Activation of the immune system during the developmental period is believed to affect the... more
The neuro-gliovascular unit is a crucial structure for providing a balanced well-functioning environment for neurons and their synapses. Activation of the immune system during the developmental period is believed to affect the gliovascular unit, which may trigger neurodevelopmental and neurological/neuropsychiatric diseases. In this study, we hypothesized that vulnerability of the male brain to a neonatal insult was conditioned by sex-dependent differences in the impairment of the hippocampal gliovascular unit. Male and female C57BL/6J pups received lipopolysaccharide (LPS) (1 mg/kg) or saline on postnatal day (P) 5. Brains were collected at P12 and morphological quantifications of hippocampal fibrillary glial acid protein (GFAP+) astrocytes and ionized calcium-binding adaptor molecule 1 protein (Iba1+) microglia were performed by using 3-D image analysis together with measuring the length of CD31+ and aquaporin-4 (AQP4+) vessels. We found a significant increase in the length of CD3...
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Antenatal brain development during the final trimester of human pregnancy is a time when mature neurons become increasingly complex in morphology, through axonal and dendritic outgrowth, dendritic branching, and synaptogenesis, together... more
Antenatal brain development during the final trimester of human pregnancy is a time when mature neurons become increasingly complex in morphology, through axonal and dendritic outgrowth, dendritic branching, and synaptogenesis, together with myelin production. Characterizing neuronal morphological development over time is of interest to developmental neuroscience and provides the framework to measure gray matter pathology in pregnancy compromise. Neuronal microstructure can be assessed with Golgi staining, which selectively stains a small percentage (1–3%) of neurons and their entire dendritic arbor. Advanced imaging processing and analysis tools can then be employed to quantitate neuronal cytoarchitecture. Traditional Golgi-staining protocols have been optimized, and commercial kits are readily available offering improved speed and sensitivity of Golgi staining to produce consistent results. Golgi-stained tissue is then visualized under light microscopy and image analysis may be co...
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Leukocyte adhesion deficiency type 1 (LAD-1) is a rare, inherited immunodeficiency that affects one per million people yearly and usually presents with recurrent, indolent bacterial infections of the skin, mouth, and respiratory tract and... more
Leukocyte adhesion deficiency type 1 (LAD-1) is a rare, inherited immunodeficiency that affects one per million people yearly and usually presents with recurrent, indolent bacterial infections of the skin, mouth, and respiratory tract and impaired pus formation and wound healing. A 13-year-old girl diagnosed LAD-I at the age of 7 years was brought to the Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, because of a draining plaque on the left leg for 2.5 years. She had recurrent skin infections and had been treated with repeated courses of different antibiotic combinations, with temporary responses, since 5 years of age. Examination revealed a 7 × 8 cm minimally erythematous hyperpigmented plaque with multiple draining sinuses on the left leg. Tissue culture yielded Pseudomonas aeruginosa. Flow cytometry showed CD18 (18.79%), CD11a (51.59%), CD11b (18.61%) and CD11c(10.60%). A plain radiography of the left leg revealed osteomyelitis. It is hi...
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Autism Spectrum Disorders (ASD) are heterogeneous neurodevelopmental disorders with considerably increased risk in male infants born preterm and with neonatal infection. Here we investigated the role of postnatal immune activation on... more
Autism Spectrum Disorders (ASD) are heterogeneous neurodevelopmental disorders with considerably increased risk in male infants born preterm and with neonatal infection. Here we investigated the role of postnatal immune activation on hippocampal synaptopathology by targeting Reelin+ cells in mice with ASD-like behavior. C57/Bl6 mouse pups of both sexes received lipopolysaccharide (LPS, 1mg/kg) on postnatal day (P) 5. At P45, animal behavior was examined by marble burying and sociability test, followed by ex-vivo brain MRI diffusion kurtosis imaging (DKI). Hippocampal synaptogenesis, number and morphology of Reelin+ cells, and mRNA expression of trans-synaptic genes, including neurexin-3, neuroligin-1, and cell-adhesion molecule nectin-1 were analyzed at P12 and P45. Social withdrawal and increased stereotypic activities in males were related to increased mean diffusivity on MRI-DKI and overgrowth in hippocampus together with retention of long-thin immature synapses on apical dendrit...
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Schizophrenia (SCZ) is a psychiatric disorder that can include symptoms of disorganized speech and thoughts with uncertain underlying mechanisms possibly linked to over‐activated microglia. In this study, we used brain samples from... more
Schizophrenia (SCZ) is a psychiatric disorder that can include symptoms of disorganized speech and thoughts with uncertain underlying mechanisms possibly linked to over‐activated microglia. In this study, we used brain samples from sixteen donors with SCZ and thirteen control donors to assess the differential activation of microglia by quantifying density and 3D reconstruction of microglia stained with ionized calcium‐binding adaptor molecule‐1 (Iba1). Our samples consisted of sections from the frontal, temporal, and cingulate cortical gray matter, subcortical white matter regions (SCWM), and included the anterior corpus callosum. In the first series of studies, we performed a density analysis followed by a spatial analysis to ascertain the microglial density, distribution, and soma size in SCZ brains. Second, we performed a series of morphological quantification techniques to investigate the arborization patterns of the microglia in SCZ. The results demonstrated an increase in micr...
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Background: Environmental Enrichment (EE) has been suggested as a possible therapeutic intervention for neurodevelopmental disorders such as autism. Although the benefits of this therapeutic method have been reported in some animal models... more
Background: Environmental Enrichment (EE) has been suggested as a possible therapeutic intervention for neurodevelopmental disorders such as autism. Although the benefits of this therapeutic method have been reported in some animal models and human studies, the unknown pathophysiology of autism as well as number of conflicting results, urge for further examination of the therapeutic potential of EE in autism. Therefore, the aim of this study was to examine the effects of environmental enrichment on autism-related behaviors which were induced in the maternal separation (MS) animal model. Material and Methods: Maternally separated (post-natal day (PND) 1–14, 3 h/day) and control male rats were at weaning (PND21) age equally divided into rats housed in enriched environment and normal environment. At adolescence (PND42–50), the four groups were behaviorally tested for direct social interaction, sociability, repetitive behaviors, anxiety behavior, and locomotion. Following completion of ...
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Inflammation and neonatal hypoxia-ischemia (HI) are important etiological factors of perinatal brain injury. However, underlying mechanisms remain unclear. Sirtuins are a family of nicotinamide adenine dinucleotide (NAD)+-dependent... more
Inflammation and neonatal hypoxia-ischemia (HI) are important etiological factors of perinatal brain injury. However, underlying mechanisms remain unclear. Sirtuins are a family of nicotinamide adenine dinucleotide (NAD)+-dependent histone deacetylases. Sirtuin-6 is thought to regulate inflammatory and oxidative pathways, such as the extracellular release of the alarmin high mobility group box-1 (HMGB1). The expression and role of sirtuin-6 in neonatal brain injury are unknown. In a well-established model of neonatal brain injury, which encompasses inflammation (lipopolysaccharide, LPS) and hypoxia-ischemia (LPS+HI), we investigated the protein expression of sirtuin-6 and HMGB1, as well as thiol oxidation. Furthermore, we assessed the effect of the antioxidant N-acetyl cysteine (NAC) on sirtuin-6 expression, nuclear to cytoplasmic translocation, and release of HMGB1 in the brain and blood thiol oxidation after LPS+HI. We demonstrate reduced expression of sirtuin-6 and increased rele...
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The fetus is strongly dependent on nutrients from the mother, including polyunsaturated fatty acids (PUFA). In adult animals, n-3 PUFA ameliorates stroke-mediated brain injury, but the modulatory effects of different PUFA content in... more
The fetus is strongly dependent on nutrients from the mother, including polyunsaturated fatty acids (PUFA). In adult animals, n-3 PUFA ameliorates stroke-mediated brain injury, but the modulatory effects of different PUFA content in maternal diet on focal arterial stroke in neonates are unknown. This study explored effects of maternal n-3 or n-6 enriched PUFA diets on neonatal stroke outcomes. Pregnant mice were assigned three isocaloric diets until offspring reached postnatal day (P) 10–13: standard, long-chain n-3 PUFA (n-3) or n-6 PUFA (n-6) enriched. Fatty acid profiles in plasma and brain of mothers and pups were determined by gas chromatography–mass spectrometry and cytokines/chemokines by multiplex protein analysis. Transient middle cerebral artery occlusion (tMCAO) was induced in P9-10 pups and cytokine and chemokine accumulation, caspase-3 and calpain-dependent spectrin cleavage and brain infarct volume were analyzed. The n-3 diet uniquely altered brain lipid profile in naï...
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Cyclic glycine-proline (cGP) is a natural nutrient of breast milk and plays a role in regulating the function of insulin-like growth factor-1 (IGF-1). IGF-1 function is essential for post-natal brain development and adult cognitive... more
Cyclic glycine-proline (cGP) is a natural nutrient of breast milk and plays a role in regulating the function of insulin-like growth factor-1 (IGF-1). IGF-1 function is essential for post-natal brain development and adult cognitive function. We evaluated the effects of cGP on spatial memory and histological changes in the hippocampus of the adult rats following infancy administration. Infant rats were treated with either cGP or saline between post-natal days 8 and 22 via oral administration to lactating dams. The spatial memory was evaluated between post-natal days 70 and 75 using Morris water maze tests. The changes of capillaries, astrocytes, synaptophysin and glutamate receptor-1 were examined in the CA1 stratum radiatum of the hippocampus. Compared to saline-treated group, cGP-treated group showed higher path efficiency of entry and lower average heading errors to the platform zone. cGP-treated group also showed longer, larger and more astrocytic processes, more capillaries and higher glutamate receptor-1 expression. The rats made less average heading error to the platform zone have more capillaries, larger and longer astrocytic branches. Thus cGP treatment/supplementation during infancy moderately improved adulthood spatial memory. This long-lasting effect of cGP on memory could be mediated via promoting astrocytic plasticity, vascularization and glutamate trafficking. Therefore, cGP may have a role in regulating IGF-1 function during brain development.
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Transient cerebral ischemia followed by reperfusion in an infarcted brain comes with predictable acute and chronic morphological alterations in neuronal and non-neuronal cells. An accurate delineation of the cerebral infarct is not a... more
Transient cerebral ischemia followed by reperfusion in an infarcted brain comes with predictable acute and chronic morphological alterations in neuronal and non-neuronal cells. An accurate delineation of the cerebral infarct is not a simple task due to the complex shapes and indistinct borders of the infarction. Thus, an exact macroscopic histological approach for infarct volume estimation can lead to faster and more reliable preclinical research results. This study investigated the effect(s) of confounding factors such as fixation and tissue embedding on the quality of macroscopic visualization of focal cerebral ischemia by anti-microtubule-associated-protein-2 antibody (MAP2) with conventional Hematoxylin and Eosin (HE) staining serving as the control. The aim was to specify the most reliable macroscopic infarct size estimation method after sub-acute focal cerebral ischemia based on the qualitative investigation. Our results showed that the ischemic area on the MAP2-stained sections could be identified macroscopically on both cryo-preserved and paraffin-embedded sections from both immersion- and perfusion-fixed brains. The HE staining did not clearly depict an infarct area for macroscopic visualization. Therefore both immersion-fixed and perfused-fixed-MAP2 stained sections can be used reliably to quantify cerebral infarcts.
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Microglia may contribute to injury but may also have neuroprotective properties. Galectin-3 has immunomodulatory properties that may affect the microglia phenotype and subsequent development of injury. Galectin-3 contributes to... more
Microglia may contribute to injury but may also have neuroprotective properties. Galectin-3 has immunomodulatory properties that may affect the microglia phenotype and subsequent development of injury. Galectin-3 contributes to experimental hypoxic-ischemic (HI) injury in the neonatal brain, but it is unclear if galectin-3 has similar effects on infectious and sterile inflammation. Thus, we investigated the effect of galectin-3 on microglia in vitro under normal as well as infectious and sterile inflammatory conditions, and the effect of galectin-3 on neonatal brain injury following an infectious challenge in vivo. Conditions mimicking infectious or sterile inflammation were evaluated in primary microglia cell cultures from newborn mice, using LPS (10 ng/mL) and TNF-α (100 ng/mL). The response to galectin-3 was tested alone or together with LPS or TNF-α. Supernatants were collected 24 h after treatment and analyzed for 23 inflammatory mediators including pro- and anti-inflammatory c...