Protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism / 中国当代儿科杂志

OBJECTIVES@#To study the protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism.@*METHODS@#A preterm rat model of brain injury caused by intrauterine inflammation was prepared by intraperitoneal injections of lipopolysaccharide in pregnant rats. The pregnant rats and preterm rats were respectively randomly divided into 5 groups: control, model, low-dose breviscapine (45 mg/kg), high-dose breviscapine (90 mg/kg), and high-dose breviscapine (90 mg/kg)+ML385 [a nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, 30 mg/kg] (n=10 each). The number and body weight of the live offspring rats were measured for each group. Hematoxylin-eosin staining was used to observe the pathological morphology of the uterus and placenta of pregnant rats and the pathological morphology of the brain tissue of offspring rats. Immunofluorescent staining was used to measure the co-expression of ionized calcium binding adaptor molecule-1 (IBA-1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex of offspring rats. ELISA was used to measure the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β) in the brain tissue of offspring rats. Western blotting was used to measure the expression of Nrf2 pathway-related proteins in the brain tissue of offspring rats.@*RESULTS@#Pathological injury was found in the uterus, and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, and severe microglia pyroptosis occurred in the cerebral cortex of the offspring rats in the model group. Compared with the control group, the model group had significant reductions in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and heme oxygenase-1 (HO-1) in the brain tissue of the offspring rats (P<0.05), but significant increases in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). Compared with the model group, the breviscapine administration groups showed alleviated pathological injury of the uterus and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, significant increases in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and HO-1 in the brain tissue of the offspring rats (P<0.05), and significant reductions in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). The high-dose breviscapine group had a significantly better effect than the low-dose breviscapine (P<0.05). ML385 significantly inhibited the intervention effect of high-dose breviscapine (P<0.05).@*CONCLUSIONS@#Breviscapine can inhibit inflammatory response in brain tissue of preterm rats caused by intrauterine inflammation by activating the Nrf2 pathway, and it can also inhibit microglial pyroptosis and alleviate brain injury.

Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice

OBJECTIVE: Ischemic stroke may result from transient or permanent reductions of regional cerebral blood flow. Polymorphonuclear neutrophils have been described as the earliest inflammatory cells to arrive in ischemic tissue. CXCR1/2 receptors are involved in the recruitment of these cells. However, the contribution of these chemokine receptors during transient brain ischemia in mice remains poorly understood. In this work, we investigated the effects of reparixin, an allosteric antagonist of CXCR1/2 receptors, in a model of middle cerebral artery occlusion and reperfusion in mice. METHODS: C57BL/6J male mice treated with reparixin or vehicle were subjected to a middle cerebral artery occlusion procedure 1 h after the treatment. Ninety minutes after ischemia induction, the monofilament that prevented blood flow was removed. Twenty-four hours after the reperfusion procedure, behavioral changes, including motor signs, were analyzed with the SmithKline/Harwell/lmperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. The animals were sacrificed, and brain tissue was removed for histological and biochemical analyses. Histological sections were stained with hematoxylin and eosin, neutrophil infiltration was estimated by myeloperoxidase activity and the inflammatory cytokine IL-iβ was measured by ELISA. RESULTS: Pre-treatment with reparixin reduced the motor deficits observed in this model of ischemia and reperfusion. Myeloperoxidase activity and IL-iβ were reduced in the reparixin-treated group. Histological analysis revealed that ischemic injury was also attenuated by reparixin pre-treatment. CONCLUSIONS: Our results suggest that the blockade of the CXCR1/2 receptors by reparixin promotes neuroprotective effects by reducing the levels of polymorphonuclear infiltration in the brain and the tissue damage associated with middle cerebral artery occlusion and reperfusion.

Accidents due to falls from roof slabs / Acidentes por queda de laje

CONTEXT AND OBJECTIVE Falls from the roof slabs of houses are accidents of high potential severity that occur in large Brazilian cities and often affect children and adolescents. The aims of this study were to characterize the factors that predispose towards this type of fall involving children and adolescents, quantify the severity of associated lesions and suggest preventive measures. DESIGN AND SETTING Descriptive observational prospective longitudinal study in two hospitals in the metropolitan region of São Paulo. METHODS Data were collected from 29 cases of falls from roof slabs involving children and adolescents between October 2008 and October 2009. RESULTS Cases involving males were more prevalent, accounting for 84%. The predominant age group was schoolchildren (7 to 12 years old; 44%). Leisure activities were most frequently being practiced on the roof slab at the time of the fall (86%), and flying a kite was the most prevalent game (37.9%). In 72% of the cases, the children were unaccompanied by an adult responsible for them. Severe conditions such as multiple trauma and traumatic brain injuries resulted from 79% of the accidents. CONCLUSION Falls from roof slabs are accidents of high potential severity, and preventive measures aimed towards informing parents and guardians about the dangers and risk factors associated with this type of accident are needed, along with physical protective measures, such as low walls around the slab and gates with locks to restrict free access to these places. .

CONTEXTO E OBJETIVO A queda de cima da laje é um acidente com alto potencial, que ocorre nas grandes metrópoles brasileiras e frequentemente acomete crianças e adolescentes. O objetivo do estudo foi caracterizar os fatores que predispõem às quedas da laje envolvendo crianças e adolescentes, quantificar a gravidade das lesões associadas e sugerir medidas preventivas. TIPO DE ESTUDO E LOCAL Estudo prospectivo longitudinal observacional de caráter descritivo realizado em dois hospitais na região metropolitana de São Paulo. MÉTODOS Foram coletados dados de 29 casos de queda da laje envolvendo crianças e adolescentes no período de outubro de 2008 a outubro de 2009. RESULTADOS O gênero masculino foi o mais prevalente, com 84% dos casos. A faixa etária predominante foi a escolar (7 a 12 anos) com 44%. O lazer foi a atividade mais frequente praticada na laje no momento da queda (86%), sendo a brincadeira de empinar pipa a mais prevalente (37,9%). Em 72% dos casos, as crianças estavam desacompanhadas de um adulto responsável. Quadros graves como politraumas e traumas cranioencefálicos representaram 79% dos acidentes. CONCLUSÃO A queda da laje representa acidente com alto potencial de gravidade, sendo necessária a adoção de medidas preventivas direcionadas ao esclarecimento de pais e responsáveis sobre os perigos e fatores de risco relacionados com esse tipo de acidente, além da adoção de medidas de proteção física, como muretas ao redor da laje e portões com travas para restringir o livre acesso a esse local. .

Remote ischaemic preconditioning and prevention of cerebral injury.

Bilateral carotid artery occlusion of 10 min followed by reperfusion for 24 hr was employed in present study to produce ischaemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Short-term memory was evaluated using elevated plus maze. Inclined beam walking test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired short-term memory, motor co-ordination and lateral push response. A preceding episode of mesenteric artery occlusion for 15 min and reperfusion of 15 min (remote mesenteric ischaemic preconditioning) prevented markedly ischaemia-reperfusion-induced cerebral injury measured in terms of infarct size, loss of short-term memory, motor coordination and lateral push response. Glibenclamide (5 mg/kg, iv) a KATP channel blocker and caffeine (7 mg/kg, iv) an adenosine receptor blocker attenuated the neuroprotective effect of remote mesenteric ischaemic preconditioning. It may be concluded that neuroprotective effect of remote mesenteric ischaemic preconditioning may be due to activation of adenosine receptors and consequent activation of KATP channels in mice.

[Investigation of TNF-alpha converting enzyme and activity of nf-kb in tolerance to ischemia induced by intermittent normobaric hyperoxia in rat model]

Recent studies suggest that intermittent and prolonged normobaric hyperoxia [HO] results in ischemic tolerance to reduce brain injury. In this research attempts were made to see the changes in TNF-alpha converting enzyme [TACE] and NF-kB activity following intermittent HO and ischemia preconditioning. The rats were divided into two experimental groups, each consisted of 20 animals. The first group was exposed to 95% inspired HO for 4h/day for 6 consecutive days [intermittent HO; InHO]. The second group acting as the control was exposed to 21% oxygen in the same chamber [normobaric normoxia or room air; RA] continuously for six days [intermittent RA; InRA]. Each main group was subdivided to MCAO-operated [middle cerebral artery occlusion], sham-operated [without MCAO], and intact [without any surgery] subgroups. After 24hr, MCAO-operated subgroups were subjected to 60 min of right MCAO. After 24 h reperfusion, neurologic deficit score [NDS] and infarct volume were assessed in MCAO-operated subgroups. Immediately and 48 h after pretreatment, blood sampling for assessment of serum TNF-alpha levels were subjected. Then, the effect of intermittent HO and ischemia on NF-kB activity and TACE expression were measured. Preconditioning with intermittent HO and ischemia decreased NDS and infarct volume. Moreover InHO and MCAO-InHO upregulate TACE and increase NF-kB activity significantly. Although further studies are needed to clarify the mechanisms of ischemic tolerance, InHO and ischemia seem to partly exert their effects via increase upregulation of TACE and NF-kB activity

Reabilitaçäo psicossocial da criança com traumatismo cranioencefálico: consequências na afetividade/emocional / Psychosocial rehabilitation of child with cranioencephalic traumatism: affectity/emotional consequences

Os autores colocam em pauta a reabilitaçäo psicossocial da criança com traumatismo cranioencefálico, em suas diferentes facetas, considerando-se os déficits físicos, cognitivos, e aspectos afetivos/emocionais. Destacam a posiçäo que os pais ocupam no momento de crise e as consequências posteriores no âmbito emocional. Ressaltam a violência que ocorre com as crianças e com os pais, decorrentes de normas culturasi e sociais. Concluem, enfatizando a responsabilidade partilhada entre pais, crianças e sociedade com respeito à questäo da prevençäo.