Expression of basic fibroblast growth factor,nerve growth factor,platelet-derived growth factor and transforming growth factor-β in human brain abscess

We correlated the histopathological findings of six human brain abscesses with the expression of basic fibroblast growth factor (bFGF), nerve growth factor (NGF), platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF). The clinical courses ranged from 1 month to 1 year and viridans streptoccus was the major pathogen. In early abscesses, we demonstrated strong bFGF and moderate NGF and PDGF immunoreactivities in neutrophils and monocytes/macrophages infiltrating the abscess wall and in the fibrin layer lining the abscess center. In the subacute cases, growth of capillaries and fibroblasts into the fibrin layer and deposition of collagen resulted in the formation of a mesodermal layer between the abscess center and the outer gliotic layer. The proliferative non-neural cells (endothelial cells, fibroblasts and glial cells) expressed mild to strong bFGF, NGF and PDGF immunoreactivities, while strong TGF staining was seen in the extracellular matrix. A loss of growth factor expression and increased fibrosis was seen in the chronic case. These findings suggest that bFGF, NGF, PDGF and TGF produced by the continued influx of leukocytes and by the proliferating non-neural cells may mediate various steps of defense mechanisms and wound healing such as angiogenesis, fibrogenesis and gliosis.Supported by NSC-82-0115-B-006-127 from the National Science Council, Republic of China     

A growth in bipolar disorder?

OBJECTIVE: This case report suggests that screening of patients with psychiatric symptoms using modern neuroimaging can help identify organic causes of mental illness. METHOD: A single case study was reported. RESULTS: We report the case of a 25-year-old woman with a recent diagnosis of bipolar II disorder having an magnetic resonance imaging (MRI) scan as part of a research project that reveals an intraventricular brain tumour. The latter is most likely the cause of her irritability and 'hypomanic' symptoms and is defined anatomically using diffusion tensor imaging and structural and functional imaging using MRI and positron emission tomography. CONCLUSION: The lesion in this individual case most probably produces mood symptoms by impinging upon the fornix, a component of the limbic system. However, more generally, the increase in diagnosis of bipolar disorder has to be tempered against alternate causes of similar symptoms and necessitates vigilance of potential organic mechanisms.     

Vascular endothelial growth factor in central nervous system injuries - a vascular growth factor getting nervous?

Vascular Endothelial Growth Factor (VEGF) is recognized as a central factor in growth, survival and permeability of blood vessels in both physiological and pathological conditions. It is as such of importance for vascular responses in various central nervous system (CNS) disorders. Accumulating evidence suggest that VEGF may also act as a neuroprotective and neurotrophic factor supporting neuronal survival and neuronal regeneration. Findings of neuropilins as shared co-receptors between molecules with such seemingly different functions as the axon guidance molecules semaphorins and VEGF has further boosted the interest in the role of VEGF in neural tissue injury and repair mechanisms. Thus, VEGF most likely act in parallel or concurrent on cells in both the vascular and nervous system. The present review gives a summary of known or potential aspects of the VEGF system in the healthy and diseased nervous system. The potential benefits but also problems and pitfalls in intervening in the actions of such a multifunctional factor as VEGF in the disordered CNS are also covered.     

Cerebrospinal nerve growth factor--a marker of asphyxia?

Asphyxia in neonates is characterized by different degrees of hypoxia-ischemia, with the outcome depending on the severity of the underlying brain cell damage. Neurotrophic factors rescue neurons from cell death after injury and promote neuronal survival during development. The authors have used enzyme-linked immunosorbent assay to study levels of nerve growth factor in the cerebrospinal fluid of children with asphyxia at birth (n = 10) and of controls (n = 23). Compared with reference groups the children who had had severe asphyxia had lower or negligible levels of cerebrospinal fluid nerve growth factor in the neonatal period or later. The level of cerebrospinal fluid nerve growth factor measured in the neonatal period was 3.76+/-4.13 pg/mL in children with asphyxia (n = 8), which is significantly lower than in children without asphyxia or infection (n = 10) 9.42+/-4.09 pg/mL or in those without asphyxia but with infection (n = 13) 17.63+/-11.48 pg/mL (P = 0.0186 and P = 0.0013, respectively). However, in some children with asphyxia the cerebrospinal fluid nerve growth factor levels were virtually normal, and most importantly these children subsequently had normal neurologic development. These results suggest that cerebrospinal fluid nerve growth factor might be used as a biochemical marker for early estimates of hypoxic-ischemic brain damage in asphyxiated neonates.     

Muscle growth: To infinity and beyond?

Strength increases following training are thought to be influenced first by neural adaptions and second by large contributions from muscle growth. This is based largely on the idea that muscle growth is a slow process and that a plateau in muscle growth would substantially hinder long‐term increases in strength. This Review examines the literature to determine the time course of skeletal muscle growth in the upper and lower body and to determine whether and when muscle growth plateaus. Studies were included if they had at least 3 muscle size time points, involved participants 18 years or older, and used a resistance training protocol. Muscle growth occurs sooner than had once been hypothesized, and this adaptation is specific to the muscle group. Furthermore, the available studies indicate that the muscle growth response will plateau, and additional growth is not likely to occur appreciably beyond this initial plateau. However, the current study durations are a limitation. Muscle Nerve 56 : 1022–1030, 2017     

Has electrical growth cone guidance found its potential?

Many neurobiologists spurn the existence and use of direct-current (DC) electric fields (EFs) in nervous system development and regeneration. This is despite direct measurement of EFs in embryos and adults, and evidence that EFs are required for normal development, dramatically influence the rate and direction of nerve growth in vitro, and promote nerve regeneration in vivo. The notion that growth cones use EFs as guidance cues was dismissed partly because there was no convincing evidence that naturally occurring EFs influence nerve growth at the single-cell level in vivo. Recent work indicates that growth cones can be guided by EFs in vivo and, intriguingly, that in vitro guidance by chemotropic gradients and EFs might invoke similar mechanisms. Ongoing clinical trials to assess the effectiveness of DC EFs in promoting the regeneration of human spinal cord could allow EFs to achieve their potential.     

Vascular endothelial growth factor induces brain erythropoietin expression?

To investigate whether the formation of vascular endothelial growth factor (VEGF) influences erythropoietin (EPO) expression in physiological conditions, we injected into the left lateral cerebral ventricle of the Mongolian gerbil an adeno-associated virus (AAV) vector capable of expressing the 165-amino-acid isoform of VEGF (VEGF165). Twelve and 18 days after AAV vector injection, the experimental animals were sacrificed and expression of EPO was evaluated through immunohistochemical analysis of both the hippocampus and the frontal cortex. We observed that VEGF165 induces EPO expression in the hippocampal pyramidal layers and in the frontal cortex of the gerbil, particularly after the 18th day following treatment with the vector, which suggests that VEGF165 could act as a hypoxic-like signal for EPO production. This finding could help to clarify the functional role of EPO and the molecular mechanisms by which VEGF might mediate its effects in the brain.     

Changes of insulin-like growth factor-Ⅱ and insulin-like growth factor binding protein-3 in cerebrospinal fluid of children with tuberculous meningitis

BACKGROUND: Recent studies have found that insulin-like growth factors (IGFs) and insulin-like growth factor binding protein-3 (IGFBP-3) have stronger neurotrophic and neuroprotective effects. But whether their levels in cerebrospinal fluid could be used as an auxiliary indicator in differentially diagnosing tuberculous meningitis and viral encephalitis is not yet clear. OBJECTIVE: To explore the changes of insulin-like growth factor-Ⅱ (IGF-Ⅱ) and IGFBP-3 in cerebrospinal fluid (CSF) of children with tuberculous meningitis and the significance of the changes. DESIGN: A non-randomized concurrent controlled study. SETTING: Department of Pediatric Internal Medicine, the First Affiliated Hospital of Xinxiang Medical College. PARTICIPANTS: Thirty children with tuberculous meningitis (14 males and 16 females) were selected from the Department of Pediatric Internal Medicine, the First Affiliated Hospital of Xinxiang Medical College from January 2005 to December 2006. Tuberculous meningitis was diagnosed according to their clinical manifestations, the history of close contact with tuberculosis, typical cerebrospinal fluid changes of tuberculous meningitis, positive tuberculosis antibody and effective antituberculosis treatment. There were 30 children (13 males and 17 females) with viral encephalitis, and viral encephalitis was diagnosed according to epidemiological history, clinical manifestations, conventional and biochemical changes of cerebrospinal fluid, and negative bacteriology judgment. Meanwhile, 30 children (13 males and 17 females) without infectious and central nervous system disease were selected as the control group. Informed consent was obtained from the parents of all the enrolled children. METHODS: ① The lumbar puncture operation was implemented immediately to obtain cerebrospinal fluid (3 mL). The contents of IGF-Ⅱ and IGFBP-3 were detected with immunoradiometric assay. The concentrations of glucose and protein in cerebrospinal fluid were determined with a dry-chemical method. The number of white blood cells was counted by Fushi Method. ② The Pearson correlation analysis was used to analyze the correlation of the contents of IGF-Ⅱ and IGFBP-3 in cerebrospinal fluid with the leucocyte counting and the concentrations of glucose and protein in cerebrospinal fluid. MAIN OUTCOME MEASURES: The contents of IGF-Ⅱ and IGFBP-3 in cerebrospinal fluid, and their correlation with the leucocyte counting and the concentrations of glucose and protein in cerebrospinal fluid. RESULTS: ① Contents of IGF-Ⅱ and IGFBP-3 in cerebrospinal fluid: The contents of IGF-Ⅱ and IGFBP-3 in cerebrospinal fluid in the tuberculous meningitis group were significantly higher than those in the encephalitis virus group and control group (P < 0.05). There was no significant difference in the contents of IGF-Ⅱ and IGFBP-3 in cerebrospinal fluid between the viral encephalitis group and control group (P > 0.05). ② Correlation: The IGF-Ⅱ and IGFBP-3 contents in cerebrospinal fluid were positively correlated with the protein concentration in cerebrospinal fluid (r =0.821, 0.855, P < 0.01), but negatively with the glucose (r =0.742, –0.605, P < 0.01). CONCLUSION: ① IGFs and IGFBPs are involved in the pathophysiological process of tuberculous meningitis, as well as the glucose and protein metabolism in cerebrospinal fluid. ② The IGF-Ⅱ and IGFBP-3 contents in cerebrospinal fluid can be used as the auxiliary indicators to differentially diagnose tuberculous meningitis and viral encephalitis.     

Circulating insulin-like growth factor 1 and insulin-like growth factor binding protein-3 level in Alzheimer’s disease: a meta-analysis

It has been reported that the associations between circulating insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) and Alzheimer’s disease (AD) are controversial. Thus, present meta-analysis was carried out to confirm the probable associations. We searched “PubMed”, “Springer” and “Medline” databases using the term (“insulin-like growth factor-1” or “IGF-1” or “insulin-like growth factor binding protein-3” or “IGFBP-3”) and (“Alzheimer’s disease”) until April 2016. Furthermore, standard mean differences (SMDs) were calculated. A total of seven reports involving 1342 percipients were pooled. SMDs were ?0.25 (P = 0.22) and ?0.33 (P = 0.08) for IGF-1 and IGFBP-3, respectively. Furthermore, the circulating IGF-1 levels in AD patients were lower than controls when studies with the difference of mean age ≤1 year (SMD ?0.57, P = 0.007) or 2 years (SMD ?0.58, P = 0.02) or difference of mean MMSE scores ≤10 scores (SMD ?0.94, P < 0.00001), or studies from Europe (SMD ?0.89, P < 0.00001) were excluded. In addition, the circulating IGFBP-3 levels in AD patients were lower than controls when studies with the difference of mean age ≤2 years (SMD ?0.62, P = 0.006) or difference of mean MMSE scores ≤6 scores (SMD ?0.48, P = 0.0004), 7 scores (SMD ?0.58, P = 0.02), or 8 scores (SMD ?0.80, P = 0.03) were excluded. Even though no significant difference of circulating IGF-1 and IGFBP-3 levels in AD patients comparing with controls was found in present meta-analysis, the current study provided the evidence that the circulating IGF-1 and IGFBP-3 level in AD patients were influenced by the difference of mean age as well as MMSE scores. Furthermore, circulating IGFBP-3 levels in AD patients may be decreased earlier than IGF-1.     

Understanding the timing of brain injury in fetal growth restriction:lessons from a model of spontaneous growth restriction in piglets

<正>Fetal growth restriction (FGR) is one of the most common contributors to increased risk of mortality in the fetal/neonatal period and long-term morbidity in the infant (Malhotra et al.,2019).FGR can arise from many pathophysiological processes associated with maternal,fetal,genetic,or placental compromise;however,placental insufficiency is the most common cause of FGR.Placental insufficiency during pregnancy results in chronic fetal hypoxia where a lack of oxygen and nutrients supply to...     

Expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor-β (PDGFR-β) in human gliomas

The growth of solid tumors is highly dependent on vascular proliferation. Vascular endothelial growth factor (VEGF), the main mediator of angiogenesis, and platelet-derived growth factor receptor-β (PDGFR-β), receptor for the potent mitogen PDGF, are two indicators of the angiogenic potential of human gliomas. We studied a series of 57 surgical biopsies of astrocytic neoplasms by immunohistochemistry to elucidate the relationship between tumor proliferation, quantified as Ki67-LI, and the expression of these two proteins. Ki67-LI increases throughout histological malignancy, although staining in endothelial cells has rarely been recorded. Elevated amounts of VEGF-positive tumor cells (VEGF-LI) were found in anaplastic astrocytomas and glioblastomas, mainly around areas of necrosis, cysts, or edema. Endothelium of blood vessels was consistently stained. PDGFR-β positivity was found in glomeruloid formations and in tumor cells, excluding pilocytic astrocytomas. Multinucleated giant cells and perivascular tumor cells were positive in glioblastomas. In addition, peritumoral microglia-like cells were also stained in some cases. Statistical correlation was only found between PDGFR-β and Ki67 LIs. In conclusion, VEGF as permeability factor is involved in the development of secondary neoplastic changes, whereas PDGFR-β is directly correlated to proliferation indexes. Strong expression of VEGF and PDGFR-β found in endothelium and tumor cells would seem to support a combined role in tumoral neoangiogenesis     

Nerve growth factor-basic fibroblast growth factor poly-lactide co-glycolid sustained-release microspheres and the small gap sleeve bridging technique to repair peripheral nerve injury

We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique. Multiple growth factors play a synergistic role in promoting the repair of peripheral nerve injury; as a result, in this study, we added basic fibroblast growth factors to the microspheres to further promote nerve regeneration. First, in an in vitro biomimetic microenvironment, we developed and used a drug screening biomimetic ...     

IL-1β inhibits axonal growth of developing sympathetic neurons

Several secreted proteins facilitate the growth and guidance of sympathetic axons to their target organs during development. Here we show that IL-1β, a key regulator of inflammation in the immune system, inhibits axonal growth and branching from cultured sympathetic neurons at a stage in development when their axons are ramifying within their targets in vivo. IL-1β is synthesised in sympathetic ganglia and its targets at this stage, and IL-1β protein is detectable in the axons and perikarya of the innervating neurons. It acts directly on developing axons to inhibit their growth via NF-κB signalling. These findings show that IL-1β is a novel locally, and target-derived factor that can regulate the extent of sympathetic axon growth during the late embryonic and early postnatal period in developing rat sympathetic neurons.     

Can amino-functionalized carbon nanotubes carry functional nerve growth factor？

Carbon nanotubes can carry protein into cells to induce biological effects. Amino-functionalized carbon nanotubes are soluble and biocompatible, have high reactivity and low toxicity, and can help promote nerve cell growth. In this study, amino-functionalized ethylenediamine-treated multi-walled carbon nanotubes were used to prepare carbon nanotubes-nerve growth factor complexes by non-covalent grafting. The physicochemical properties, cytotoxicity to PC12 and chick embryo dorsal root ganglion, and biological activity of the carbon nanotubes-nerve growth factor complexes were investigated. The results showed that amino functionalization improved carbon nanotubes-nerve growth factor complex dispersibility, reduced their toxicity to PC12 cells, and promoted PC 12 cell differentiation and chick embryo dorsal root ganglion.