The specific protective mechanism of mitophagy and Nrf2 in brain injury has not been fully clarified. This study aimed to reveal the effect of Nrf2 on hydraulic shock brain injury in mice, and explore its possible mechanism. Twenty-four Nrf2 knockout (Nrf2-/-) and wild-type mice (WT) of C57BL/6J were randomly divided into two groups: control group (C) and brain injury group (TBI). Hematoxylin-eosin staining (HE) assay was used for the histomorphological observation. The apoptotic state of brain tissue was detected by TUNEL. Mechanical damage in vitro models of glial cells were prepared. The wild-type (WT) and Nrf2 knockout (KO) mice were constructed to investigate the changes of mitophagy and apoptosis-related indicators by Western blotting. The experimental results showed that 24 h after TBI, the tissue structure was highly porous, the cells were highly edema, the neuronal space increased significantly, the neuron degeneration, and the cell vacuolation was obvious. Meanwhile, the number of apoptotic cells and the apoptosis rate of glial cells increased significantly. After injury, the relative expression of Parkin, Pink, Beclin and LC-3II proteins were significantly decreased in all mice. The protein expressions of Caspase3 and Caspase12 were significantly increased. However, in the TBI group, KO mice were more impaired than WT mice. In conclusion, Nrf2 plays a protective role by promoting mitophagy to inhibit apoptosis in the process of brain injury caused by hydraulic shock in mice, which provides a new idea for the effective treatment of brain injury.
Hemorrhagic shock is associated with activation of renin-angiotensin system (RAS) and endoplasmic reticulum stress (ERS). Previous studies demonstrated that central RAS activation produced by various challenges sensitizes angiotensin (Ang) II-elicited hypertension and that ERS contributes to the development of neurogenic hypertension. The present study investigated whether controlled hemorrhage could sensitize Ang II-elicited hypertension and whether the brain RAS and ERS mediate this sensitization. Results showed that hemorrhaged (HEM) rats had a significantly enhanced hypertensive response to a slow-pressor infusion of Ang II when compared to sham HEM rats. Treatment with either angiotensin-converting enzyme (ACE) 1 inhibitor, captopril, or ACE2 activator, diminazene, abolished the HEM-induced sensitization of hypertension. Treatment with the ERS agonist, tunicamycin, in sham HEM rats also sensitized Ang II-elicited hypertension. However, blockade of ERS with 4-phenylbutyric acid in HEM rats did not alter HEM-elicited sensitization of hypertension. Either HEM or ERS activation produced a greater reduction in BP after ganglionic blockade, upregulated mRNA and protein expression of ACE1 in the hypothalamic paraventricular nucleus (PVN), and elevated plasma levels of Ang II but reduced mRNA expression of the Ang-(1-7) receptor, Mas-R, and did not alter plasma levels of Ang-(1-7). Treatment with captopril or diminazene, but not phenylbutyric acid, reversed these changes. No treatments had effects on PVN protein expression of the ERS marker glucose-regulated protein 78. The results indicate that controlled hemorrhage sensitizes Ang II-elicited hypertension by augmenting RAS prohypertensive actions and reducing RAS antihypertensive effects in the brain, which is independent of ERS mechanism.
目的 总结儿童桥本脑病(HE)的临床特征.方法 纳入2017年1月至2020年12月河北省儿童医院神经科收治的HE患儿,回顾性分析患儿的临床表现、实验室检查、头颅MR、治疗和随访情况.结果 7例HE中,男5例,发病年龄5~12岁.3例病初伴发热,起病前有感染史、病毒性脑炎史、食欲亢进及排便增多、癫(癇)病史各1例.癫(癇)发作3例,2例为癫(癇)持续状态;精神行为异常和意识状态改变各3例;外展神经受损1例.血常规WBC、CRP升高1例;脑脊液细胞数和蛋白升高分别为3和1例;5例行寡克隆区带检测2例阳性.甲状腺过氧化物酶抗体(TPO)3例起病时即升高,4例2周内升高.入院时甲亢和中枢性甲减各2例,低T3综合征、fT3和fT4均降低各1例,1例入院后中枢性甲减;2例甲状腺超声示多囊性小结节.3例头颅MR有异常表现;脑电图均表现为不同程度的慢波发放,1例检测到癫(癇)波.均予免疫球蛋白冲击联合大剂量甲泼尼龙琥珀酸钠治疗,6例治疗3~8 d后症状缓解,1例1个月后未改善,第2轮激素治疗7 d后症状缓解.随访1~4年,1例复发2次,予激素或免疫球蛋白冲击治疗后症状缓解.3例头颅MR异常者在2个月内随访影像学均恢复正常.4例随访复查TPO抗体,3例仅随访甲状腺功能,均在发病1年内恢复正常.结论 儿童HE的临床表现、实验室指标和影像学表现缺乏特异性,需与多种疾病进行鉴别诊断.对于不明原因的脑病患儿,在除外自身免疫性脑炎、炎症和脱髓鞘疾病后要警惕HE的可能,应多次检测TPO抗体,以协助诊断.
IntroductionThe total resection rate of large intracranial tumors was significantly improved with the great advances of microneurosurgical techniques and the application of a series of haemostatic materials [1].Mortality and disability were significantly lower, however, postoperative complications, which are the main problems of neurosurgeon, are life-threatening events that clinicians need to take as a possible risk [2].After the resection of giant intracranial tumor, there are many complications caused by residual cavity which include acute subdural hematoma (SDH), remote epidural hematoma (EDH), residual cavity hematoma (RCH), ischemic cerebral infarction, subcutaneous and tumor cavity tension effusion.A possible mechanism is proposed to explain this phenomenon and cavity-related complications have been successfully avoided by applying Foley balloon catheter after the resection of giant intracranial tumor.
Abstract Rationale: Subacute combined degeneration (SCD) is a disease caused by decreased vitamin B12 intake or metabolic disorders. It is more common in the elderly and rarely seen in children. Here, we report 2 pediatric cases of SCD in late-onset cobalamin C (CblC) deficiency. Patient concerns: The patients complained of unsteady gait. Their physical examination showed sensory ataxia. Magnetic resonance imaging showed classic manifestations of SCD. The serum vitamin B12 level was normal, but urine methylmalonic acid and serum homocysteine levels were high. Diagnosis: The pathogenic gene was confirmed as MMACHC. The 2 patients each had 2 pathogenic mutations C.482 G>A and C.271dupA and C.365A>T and C.609G>A in this gene. They were diagnosed with combined methylmalonic acidemia and homocysteinemia-CblC subtype. Interventions: The patients were treated with methylcobalamin 500 μg intravenous injection daily after being admitted. After the diagnosis, levocarnitine, betaine, and vitamin B12 were added to the treatment. Outcomes: Twelve days after treatment, the boy could walk normally, and his tendon reflex and sense of position returned to normal. The abnormal gait seemed to have become permanent in the girl and she walked with her legs raised higher than normal. Lessons: To the best of our knowledge, this is the first report of 2 cases of isolated SCD in children with late-onset CblC disorder. Doctors should consider that SCD could be an isolated symptom of CblC disorder. The earlier the treatment, the lower the likelihood of sequelae.
目的 探讨注意力缺陷多动障碍(ADHD)患儿与正常儿童相比血清25羟维生素D[25(OH)D]的变化情况.方法 纳人的研究类型为病例对照研究,病例组为新诊断的ADHD患儿(诊断标准不限),对照组为健康儿童,暴露因素为血清25(OH)D(测定方法不限;测定时问为初次诊断ADHD时,且尚未经过药物治疗),排除伴有孤独症谱系障碍、抑郁症等其他精神心理疾病的患儿.计算机检索PubMed、Embase和Cochrane数据库,万方和中国知网数据库,检索时问为建库至2018年3月3日,检索策略为主题词和自由词结合.按照纽卡斯尔-渥太华量表(NOS)进行文献质量评价,采用RevMan 5.3软件进行数据分析.结果 8篇文献进人Meta分析,ADHD组共2279例,健康对照组共5532例.8篇文献NOS评价均≥7颗星,研究对象1篇来源于社区,6篇来源于医院门诊,1篇未描述研究对象来源.8篇文献均采用随机效应模型合并(P<0.00001、I2=88%),ADHD组血清25(OH)D较对照组低6.5 ng·mL-1(WMD=-6.52,95%CI:-8.40~-4.64).亚组分析显示,采用不同的25(OH)D检测方法,包括化学发光免疫分析法(CLIA)、酶联免疫吸附法(ELISA)和放射免疫法(RIA)检测25(OH)D的文献,ADHD组与对照组的25(OH)D值差异均有统计学意义;采用DSM-Ⅴ/Ⅳ诊断标准的文献,ADHD组和对照组25(OH)D值差异有统计学意义;研究对象为门诊来源的文献,ADHD组和对照组25(OH)D值差异有统计学意义.结论 ADHD患儿初诊时血清25(OH)D水平低于健康儿童.
Objective This study is performed to evaluate feasibility on treating non-thalamus supratentorial HICH with sequencing treatment. Methods Retrospective analysis of 110 cases( 43 cases in sequencing treatment and 67cases in non-sequencing treatment) with HICH within 72 h in the Second Hospital of Hebei Medical University from November 2011 to October 2012. Comparing the difference in hospitalization,expenditure,incidence of pulmonary infection,mortality and modified Rankin score( mRS) at 1st and 3rd month after stroke.Results There was no statistically significant difference in hospital day,expenditure and one month mortality between two groups( P0.05),whereas have significantly difference in mortality at 3rd month,incidence of pulmonary infection and mRS during one and three months after onset( P0.05).Conclusions Preliminary research shows that schedule of sequencing treatment have important clinical value in dealing with supratentorial non- thalamus( HICH) include improving prognosis and reducing incidence of pulmonary infection. That need further confirmed by prospective multicenter clinical control study.