RESUMO
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 CD31+ capillaries in the male LPS group compared to the saline group; however, coverage of capillaries by astrocytic end-feet (AQP4+) was significantly reduced. In contrast, there was a significant increase in AQP4+ capillary length in female pups 1 week after LPS injection. GFAP+ astrocytes via morphological changes in the hippocampus showed significant enhancement in the activity 1 week following LPS injection in male mice. We propose that neonatal inflammation could induce susceptibility to neurodevelopmental disorders through modification of hippocampal gliovascular interface in a sex-dependent manner.
Assuntos
Astrócitos , Lipopolissacarídeos , Animais , Astrócitos/metabolismo , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
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 cytokines and chemokines using multiplex protein analysis, as well as ELISA for MCP-1 and insulin-like growth factor (IGF)-1. Phosphorylation of proteins (AKT, ERK1/2, IκB-α, JNK, and p38) was determined in microglia cells. Neonatal brain injury was induced by a combination of LPS and HI (LPS + HI) in postnatal day 9 transgenic mice lacking functional galectin-3 and wild-type controls. LPS and TNF-α induced pro-inflammatory (9/11 vs. 9/10) and anti-inflammatory (6/6 vs. 2/6) cytokines, as well as chemokines (6/6 vs. 4/6) in a similar manner, except generally lower amplitude of the TNF-α-induced response. Galectin-3 alone had no effect on any of the proteins analyzed. Galectin-3 reduced the LPS- and TNF-α-induced microglia response for cytokines, chemokines, and phosphorylation of IκB-α. LPS decreased baseline IGF-1 levels, and the levels were restored by galectin-3. Brain injury or microglia response after LPS + HI was not affected by galectin-3 deficiency. Galectin-3 has no independent effect on microglia but modulates inflammatory activation in vitro. The effect was similar under infectious and sterile inflammatory conditions, suggesting that galectin-3 regulates inflammation not just by binding to LPS or toll-like receptor-4. Galectin-3 restores IGF-1 levels reduced by LPS-induced inflammation, suggesting a potential protective effect on infectious injury. However, galectin-3 deficiency did not affect microglia activation and was not beneficial in an injury model encompassing an infectious challenge.
Assuntos
Lesões Encefálicas , Hipóxia-Isquemia Encefálica , Animais , Animais Recém-Nascidos , Galectina 3 , Inflamação , Lipopolissacarídeos/toxicidade , Camundongos , MicrogliaRESUMO
OBJECTIVE: The aim of this study was to determine the association between previously documented risk factors such as recurrent pyelonephritis with the incidence of renal scarring after acute pyelonephritis in children. MATERIAL AND METHODS: Children with acute pyelonephritis who were admitted to the Department of Pediatrics of a teaching hospital during 2007-2009 were enrolled in this study. DMSA scans were obtained 4-6 months after the last episode of pyelonephritis in all patients. RESULTS: A total of 80 children with acute pyelonephritis were enrolled in this study. Most of them were girls (77.5%), with a median age of 12 months. Nearly half of the children (n = 44; 55%) had one or more renal scars. The distribution of gender, CRP level and leukocytosis did not differ significantly regarding the absence or presence of renal scars (p > 0.05). Most of the scars occurred in children who had presented with bilateral pyelonephritis (69.4% vs. 18.2%, p = 0.001). Most of the patients with renal scars had a positive history of vesicoureteral reflux (VUR) (75% vs.13.6%, p = 0.001). The significant roles of recurrent pyelonephritis and presence of VUR were further confirmed by multivariate analysis. CONCLUSIONS: According to our findings, presence of VUR and recurrent pyelonephritis are independently associated with a higher incidence of renal scarring.
Assuntos
Cicatriz/etiologia , Rim , Pielonefrite/complicações , Doença Aguda , Criança , Pré-Escolar , Cicatriz/diagnóstico por imagem , Feminino , Humanos , Lactente , Rim/diagnóstico por imagem , Masculino , Estudos Prospectivos , Pielonefrite/diagnóstico por imagem , Cintilografia , Compostos Radiofarmacêuticos , Recidiva , Fatores de Risco , Ácido Dimercaptossuccínico Tecnécio Tc 99mRESUMO
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.
Assuntos
Artrite Juvenil/epidemiologia , Deficiência de IgA/epidemiologia , Adolescente , Artrite Juvenil/diagnóstico , Estudos de Casos e Controles , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Transtornos do Crescimento/epidemiologia , Humanos , Deficiência de IgA/diagnóstico , Imunoglobulinas/sangue , Irã (Geográfico)/epidemiologia , Masculino , Nefelometria e Turbidimetria , PrevalênciaRESUMO
OBJECTIVE: The aim of this study was to determine the association between previously documented risk factors such as recurrent pyelonephritis with the incidence of renal scarring after acute pyelonephritis in children. MATERIAL AND METHODS: Children with acute pyelonephritis who were admitted to the Department of Pediatrics of a teaching hospital during 2007-2009 were enrolled in this study. DMSA scans were obtained 4-6 months after the last episode of pyelonephritis in all patients. RESULTS: A total of 80 children with acute pyelonephritis were enrolled in this study. Most of them were girls (77.5 percent), with a median age of 12 months. Nearly half of the children (n = 44; 55 percent) had one or more renal scars. The distribution of gender, CRP level and leukocytosis did not differ significantly regardingthe absence or presence of renal scars (p > 0.05). Most of the scars occurred in children who had presented with bilateral pyelonephritis (69.4 percent vs. 18.2 percent, p = 0.001). Most of the patients with renal scars had a positive history of vesicoureteral reflux (VUR) (75 percent vs.13.6 percent, p = 0.001). The significant roles of recurrent pyelonephritis and presence of VUR were further confirmed by multivariate analysis. CONCLUSIONS: According to our findings, presence of VUR and recurrent pyelonephritis are independently associated with a higher incidence of renal scarring.