Modulation of hypoxia inducible factor-1 alpha in neurons after cerebral hypoxia by recombinant adenovirus-mediated hypoxia inducible factor-1 alpha / 中华老年医学杂志

Objective:To investigate the regulatory effects and possible mechanisms of recombinant adenovirus-mediated hypoxia inducible factor-1 alpha(HIF-1α)transfection on HIF-1α in post-hypoxic rat cortical neurons.Methods:(1)Preparation of rats' cerebral cortical neurons in primary culture and hypoxia model.Recombinant adenovirus-mediated HIF-1α(AdHIF-1α)transfection and recombinant Ad transduction in normal and hypoxic cells.Then they will be divided into normal control group, hypoxia group, the recombinant adenovirus hypoxia-inducible factor-1α(AdHIF-1α)gene transfection group and recombinant adenovirus empty vector(Ad)transfection group.(2)To observe the transfection of AdHIF-1α/ Ad under fluorescence microscopy.The expression of hypoxia-inducible factor-1 alpha(HIF-1α)were observed by Western blot analysis in each group of neurons at 12 h、24 h、48 h and 72 h.Results:Hypoxic neurons transfected with Ad/AdHIF-lα showed the obvious expression 48 h under fluorescence microscopy.At each time of the AdHIF-1α gene transfection group, the expression of HIF-1α is significantly increased, the positive expression emerges at 12 h, the expression increased at 24 h, and it reaches the peak at 48 h, until 72 h declines, and it has statistical significance compared with the hypoxia group( P<0.01, P<0.05), but the Ad group has no statistically significant differences compared with the hypoxia group. Conclusions:The transfection of recombinant adenovirus-mediated HIF-1α gene can significantly increase the expression levels of HIF-1α in hypoxic neurons, and it may play a protective role in the neurons after hypoxia.

Cognitive function changes and their influential factors in patients with ischemic stroke and leukoaraiosis / 中国基层医药

Objective:To investigate cognitive function changes and their influential factors in patients with ischemic stroke and leukoaraiosis.Methods:A total of 500 patients with ischemic stroke who received treatment in Yiwu Central Hospital from January 2018 to October 2019 were included in this study. They were divided into simple ischemic stroke group ( n = 200) and ischemic stroke complicated by leukoaraiosis group (combination group, n = 300). The infarct location and the degree of leukoaraiosis in the combination group were analyzed. An additional 150 volunteers who concurrently underwent the Cognitive Function Test in the same hospital were selected as controls. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). Patients in the combination group were divided into cognitive impairment group (MoCA score ≥ 26 points) and non-cognitive impairment group (MoCA score < 26 points) according to MoCA score. The risk factors of cognitive impairment in patients with ischemic stroke and leukoaraiosis were analyzed. Results:The scores of the MMSE, MoCA, Clock Drawing Test (CDT), Verbal Fluency Test (VFT), and Digit Span Test (DST) in the control group were (28.93 ± 2.70) points, (28.35 ± 2.74) points, (4.69 ± 1.14) points, (4.94 ± 0.42) points, and (14.33 ± 1.66) points respectively. They were (26.92 ± 2.18) points, (25.02 ± 3.52) points, (3.61 ± 1.60) points, (4.77 ± 0.46) points, and (11.73 ± 1.16) points, respectively in the simple ischemic stroke group and (24.91 ± 2.79) points, (20.70 ± 3.06) points, (2.87 ± 1.23) points, (4.07 ± 0.85) points, and (10.82 ± 0.93) points respectively in the combination group. There were significant differences in the scores of the MMSE, MoCA, CDT, VFT, and DST among the three groups ( F = 124.50, 318.50, 93.43, 112.60, 428.60, all P < 0.001). Significant differences in the scores of the MMSE, MoCA, CDT, VFT, and DST were observed between patients with different degrees of leukoaraiosis ( F = 69.09, 102.40, 20.98, 60.90, 57.00, all P < 0.001). Spearman correlation analysis results showed that the scores of the MMSE, MoCA, CDT, VFT, and DST were negatively correlated with the degree of leukoaraiosis ( r = -0.61, -0.69, -0.43, -0.56, -0.44, all P < 0.05). Logistic regression analysis results showed that age, history of smoking and drinking, history of diabetes, history of stroke, and infarct location were the independent risk factors for cognitive impairment in patients with ischemic stroke and leukoaraiosis. Education level was a protective factor against ischemic stroke and leukoaraiosis. Conclusion:The degree of cognitive impairment in patients with ischemic stroke and leukoaraiosis is related to the degree of leukoaraiosis. Age, history of smoking and drinking, history of diabetes, history of stroke, infarction location, and education level are the influential factors of cognitive impairment.

Leucoencefalopatia tóxica por inhalación de heroína "Chasing the Dragon": serie de casos / Toxic Leukoencephalopathy by inhaling heroin "Chasing the Dragon": case series

RESUMEN INTRODUCCIÓN: La leucoencefalopatia tóxica es una afección que compromete la sustancia blanca por exposición a sustancias tóxicas. La heroina es una de las implicadas en el desarrollo de la leucoencefalopatia con diferencias exclusivas que suceden con la inhalación según las diversas técnicas en comparación al uso intravenoso, bien sea de la heroína o de otras sustancias psicoactivas. En esta serie describimos cinco casos, de sexo masculino, que desarrollaron leucoencefalopatia espongiforme por heroína (LEH) posterior a la inhalación de vapores, en un hospital del sistema de salud público en la ciudad de Armenia, Colombia. OBJETIVO: El objetivo de este estudio es describir las características demográficas, clínicas, hallazgos de laboratorio e imágenes diagnósticas, así como la mortalidad asociada a LEH en la muestra estudiada. MÉTODOS: Recolección de datos de historias clinicas y búsqueda de imágenes registradas en el Hospital San Juan de Dios de Armenia durante el periodo 2017-2018. RESULTADOS: Se obtienen cinco casos clínicos de pacientes usuarios de vapores inhalados de heroina, quienes ingresan con signos neurológicos de predominio motores y extrapiramidales, con el signo radiológico clásico de "Chasing the Dragon" en estudios de TC cerebral simple en todos los casos. De los cinco casos se presenta un deceso, determinando una mortalidad de 20% comparado con un 25% de mortalidad reportado en la literatura. CONCLUSIONES: La LEH suele estar subdiagnosticada dado que suele confundirse con un trastorno neuropsiquiatríco o de la conducta asociada al consumo de sustancias psicoactivas (SPA), el diagnóstico se realizó con los hallazgos típicos en las imágenes de TC cerebral simple. Se debe tener en cuenta las estadísticas sobre consumo de heroína a la hora de realizar el abordaje de un paciente con historial de consumo de SPA y los signos neurológicos para relacionarlos con esta etiologia y dar un manejo integral a estos pacientes.

ABSTRACT IlNTRODUCTION: Toxic leukoencephalopathy is a condition that compromises the encephalic white matter due to exposure to toxic substances. Heroin is one of those involved in the development of leukoencephalopathy and there are certain differences that occur with its inhalation with the different techniques compared to intravenous use, either heroin or other psychoactive substances. In this serie, we describe five cases of male sex who developed heroin spongiform leukoencephalopathy (HSLE) after inhalation of vapors, in a Hospital of the public health system in the city of Armenia, Colombia. OBJECTIVES: The objective of this study is to describe the demographic and clinical characteristics, laboratory findings and diagnostic images, as well as the mortality associated with HSLE in the sample studied. METHODS: Collection of data from medical records and search of images registered at the San Juan de Dios Hospital in Armenia during the period 2017-2018. RESULTS: Five clinical cases were obtained of patients who were users of inhaled heroin vapors and were admitted to the hospital with predominantly motor and extrapyramidal neurological signs, with simple brain CT studies showing the classic radiological sign of "Chasing the Dragon" in all five cases. One death was presented, with a mortality of 20% compared to the 25% mortality that has been reported in the scientific literature. CONCLUSIONS: HSLE is usually underdiagnosed since it is often confused with a neuropsychiatric or behavioral disorder associated with the consumption of psychoactive substances (PAS). The diagnosis was made with the typical findings in simple brain CT images. Statistics on heroin use must be considered when approaching a patient with a history of PAS use and neurological signs, to relate them to this etiology and provide comprehensive management to these patients.

Predictive value of early cerebral oxygen utilization combined with the bispectral index for delayed encephalopathy after acute carbon monoxide poisoning in elderly patients / 中华老年医学杂志

Objective:To investigate clinical value of early cerebral oxygen utilization(O 2UCc)combined with the bispectral index(BIS)for monitoring delayed encephalopathy after acute carbon monoxide poisoning(DEACMP)in elderly patients. Methods:This was a retrospective analysis.A total of 90 elderly patients with acute severe carbon monoxide poisoning(ASCMP)treated in Harrison International Peace Hospital from Nov.2018 to Jan.2020 were considered as research objects.Patients were divided into the DEACMP group(n=25)and the good prognosis group(n=65)according to their prognosis.Oxygen quantity absorbed into UCC(O 2UCc)and Bispectral index(BIS)at different times in the early stages were compared between the two groups.Correlations of O 2UCc and BIS with the occurrence of DEACMP were analyzed.Clinical significance of O 2UCc or BIS alone and of the two parameters in combination for the prediction of DEACMP was investigated. Results:O 2UCc was higher and BIS was lower in the DEACMP group than in the good prognosis group at 0 h, 6 h, 12 h, and 24 h after admission(all P<0.01). Pearson correlation analysis showed that O 2UCc was negatively correlated with DEACMP( r0 h=-0.482, r6 h=-0.534, r12 h=-0.587, r24 h=-0.514, all P<0.01), BIS was positively correlated with DEACMP( r0 h=0.348, r6 h=0.583, r12 h=0.679, r24 h=0.489, all P<0.01), and the correlation was the strongest at 12h after admission.ROC curve analysis was performed with O2UCc, BIS and the combined predictors at 12 h, and the results showed that the areas under the ROC curve of O 2UCc, BIS and the two in combination for DEACMP prediction were 0.845, 0.850 and 0.909, respectively, the sensitivities were 78.5%, 90.8% and 96.9% and the specificities were 80.0%, 76.0% and 84.0%, respectively. Conclusions:Early detection of O 2UCc or BIS has a good clinical value for predicting the development of ASCMP to DEACMP, and their combined value is even better.

Effect of propofol postconditoning on Rb-E2F1 signaling pathway in hippocampal neurons in a rat model of oxygen-glucose deprivation and restoration / 中华麻醉学杂志

Objective:To evaluate the effect of propofol postconditoning on retinoblastoma protein (Rb)-E2F1 signaling pathway in hippocampal neurons in a rat model of oxygen-glucose deprivation and restoration (OGD/R).Methods:Pregnant Wistar rats at 16-18 days of gestation were sacrificed, and the hippocampal neurons of fetal rats were obtained and primarily cultured for 7 days.The neurons were divided into 3 groups ( n=42 each) using a random number table method: control group (group C), OGD/R group (group O) and propofol postconditoning group (group P). In group O, the neurons were subjected to oxygen-glucose deprivation for 1 h, followed by restoration of oxygen-glucose.In group P, propofol (final concentration 1.2 μg/ml) was added immediately after restoration of oxygen and glucose, and the cells were cultured for 2 h and then the culture medium was replaced with plain culture medium.At 24 h of culture, the expression of p-Rb and E2F1 was determined by Western blot, and the cell cycle and apoposis rate were assessed by flow cytometry. Results:Compared with group C, the apoptosis rate was significantly increased, expression of p-Rb and E2F1 was up-regulated, the ratio of p-Rb nuclear/plasmosin protein and the proportion of neurons in G 0/G 1 phase were decreased, and the proportion of neurons in S and G 2/M phases was increased in O and P groups ( P<0.05). Compared with group O, the apoptosis rate was significantly decreased, expression of p-Rb and E2F1 was down-regulated, the ratio of p-Rb nuclear/plasmosin protein and the proportion of neurons in G 0/G 1 phase were increased, and the proportion of neurons in S and G 2/M phases was decreased in group P ( P<0.05). Conclusion:The mechanism by which propofol postconditioning decreases the apoptosis in hippocampal neurons is related to inhibiting Rb-E2F1 signaling pathway in a rat model of OGD/R.

Research progresses of neonatal cerebral network reorganization following hypoxic ischemic injury / 中国医学影像技术

Hypoxic ischemia (HI) is a fatal cause of neonatal encephalopathy and death. The developing brain can adjust the structures and function of brain according to different states due to neural plasticity. Understanding the pathophysiological process and cerebral network reorganization of neural damage after HI is very important for early diagnosis and intervention of disease. The research progresses of mechanism of neonatal cerebral network reorganization following HI were reviewed in this article.

Hipotermia neuroprotetora tardia / Late hypothermic neuroprotection

A parada cardiorrespiratória é um evento de alta mortalidade. A isquemia cerebral difusa relacionada ao hipofluxo cerebral frequentemente leva à injúria neurológica grave e ao desenvolvimento de estado vegetativo persistente. A hipotermia terapêutica representa um importante avanço no tratamento da encefalopatia anóxica pós-parada cardíaca. Seus efeitos neuroprotetores têm sido amplamente demonstrados em várias situações de isquemia neuronal. Apesar de ser um procedimento associado com redução de mortalidade nestes pacientes, a hipotermia ainda é um tratamento subutilizado no manejo da síndrome pós-ressuscitação. Nosso objetivo foi demonstrar que a hipotermia neuroprotetora tem efeito benéfico mesmo realizada tardiamente naqueles pacientes comprovadamente encefalopatas como consequência de baixo fluxo cerebral devido à parada cardiorrespiratória que mantém um nível neurológico baixo (Glasgow abaixo de 8). Este fato é demonstrado pelo não uso de substâncias neurodepressoras nas últimas 48 horas, e o ganho para o paciente seria maior que os prováveis riscos que a hipotermia pode ocasionar. Este relato mostra os efeitos benéficos no paciente submetido ao tratamento da hipotermia neuroprotetora tardiamente, evoluindo satisfatoriamente, visto que foi devolvido à sociedade em Glasgow 14 e com independência suficiente para atender suas necessidades humanas básicas. Era um paciente do sexo masculino, 25 anos, pardo, solteiro, imigrante ilegal oriundo da Bolívia, auxiliar de costura, com história de mal súbito enquanto praticava futebol com amigos em quadra ao ar livre. Deu entrada no pronto-socorro em parada cardiorrespiratória por taquicardia ventricular. Foram realizadas manobras de reanimação com cardioversão elétrica e massagem cardíaca e não houve relato do tempo de parada cardíaca. Foi transferido para a unidade de terapia intensiva adulto com hipótese diagnóstica de encefalopatia anóxica pós-parada cardiorrespiratória sem uso de drogas vasoativas em Glasgow 6.(AU)

Cardiac arrest is a high-mortality event. Brain hypoflow-related diffuse cerebral ischemia often leads to severe neurological injury, and to the development of a persistent vegetative state. Therapeutic hypothermia is an important advance in the treatment of anoxic encephalopathy after cardiac arrest. Its neuroprotective effects have been widely demonstrated in several situations of neuronal ischemia. Although the procedure is associated with reduced mortality, hypothermia is still an underused treatment in the management of post-resuscitation syndrome. Our goal was to demonstrate that neuroprotective hypothermia is effective even when performed late in patients with encephalopathies from brain hypoflow due to cardiac arrest with a low neurological level (Glasgow below 8). This is demonstrated by the lack of neurodepressant substances in the previous 48 hours, and patient benefit would be higher than the probable risks that hypothermia could cause. This report shows the beneficial effects in the patient undergoing delayed neuroprotective hypothermia, who progressed satisfactorily, since taken back to Glasgow 13 with sufficient independence to meet basic human needs. The patient was a male of 25 years old, dark-skinned, single, an illegal immigrant from Bolivia, sewing assistant, with a history of sudden cardiac arrest, which occured while playing soccer outdoors. He was admitted to the emergency room in cardiopulmonary arrest (CPA) due to ventricular tachycardia. Resuscitation maneuvers with electrical cardioversion and cardiac massage were performed, and there is no reported time of cardiac arrest. He was transferred to the Adult Intensive Care Unit with a diagnosis hypothesis of anoxic encephalopathy after cardiac arrest, with no use of vasoactive drugs in Glasgow 6.(AU)

Risk factors associated with the development of perinatal asphyxia in neonates at the Hospital Universitario del Valle, Cali, Colombia, 2010-2011 / Factores de riesgo asociados con el desarrollo de asfixia perinatal en neonatos en el Hospital Universitario del Valle, Cali, Colombia, 2010-2011

Abstract Introduction: Perinatal asphyxia is one of the main causes of perinatal mortality and morbidity worldwide and it generates high costs for health systems; however, it has modifiable risk factors. Objective: To identify the risk factors associated with the development of perinatal asphyxia in newborns at Hospital Universitario del Valle, Cali, Colombia. Materials and methods: Incident cases and concurrent controls were examined. Cases were defined as newborns with moderate to severe perinatal asphyxia who were older than or equal to 36 weeks of gestational age, needed advanced resuscitation and presented one of the following: early neurological disorders, multi-organ commitment or a sentinel event. The controls were newborns without asphyxia who were born one week apart from the case at the most and had a comparable gestational age. Patients with major congenital malformations and syndromes were excluded. Results: Fifty-six cases and 168 controls were examined. Premature placental abruption (OR=41.09; 95%CI: 4.61-366.56), labor with a prolonged expulsive phase (OR=31.76; 95%CI: 8.33-121.19), lack of oxytocin use (OR=2.57; 95% CI: 1.08 - 6.13) and mothers without a partner (OR=2.56; 95% CI: 1.21-5.41) were risk factors for the development of perinatal asphyxia in the study population. Social difficulties were found in a greater proportion among the mothers of cases. Conclusions: Proper control and monitoring of labor, development of a thorough partograph, and active searches are recommended to ensure that all pregnant women have adequate prenatal care with the provision of social support to reduce the frequency and negative impact of perinatal asphyxia.

Resumen Introducción: La asfixia perinatal constituye una de las principales causas de morbilidad y mortalidad perinatal en el mundo, tiene factores de riesgo modificables y genera altos costos para los sistemas de salud. Objetivo: Determinar los factores de riesgo asociados al desarrollo de asfixia perinatal en recién nacidos en el Hospital Universitario del Valle, Cali, Colombia. Materiales y métodos: Se llevó a cabo un estudio de casos incidentes y controles concurrentes. Los casos se definieron como neonatos con asfixia perinatal moderada a grave, de edad de gestación mayor o igual a 36 semanas, que requirieron reanimación avanzada y presentaron, al menos, una de las siguientes condiciones: alteraciones neurológicas tempranas, falla orgánica múltiple o aparición de un evento centinela. Los controles se definieron como neonatos sin diagnóstico de asfixia, nacidos hasta con una semana de diferencia con respecto al caso y de edad de gestación comparable. Se excluyeron los pacientes con malformaciones congénitas mayores y síndromes. Resultados: Se estudiaron 56 casos y 168 controles. El desprendimiento prematuro de la placenta (odds ratio, OR=41,09; IC95% 4,61-366,56), un trabajo de parto con fase expulsiva prolongada (OR=31,76; IC95% 8,33-121,19), no usar oxitocina (OR=2,57; IC95% 1,08-6,13) y ser madre soltera (OR=2,56; IC95% 1,21-5,41) fueron factores de riesgo para el desarrollo de asfixia perinatal en la población bajo estudio. En las madres de los casos se encontraron dificultades sociales en mayor proporción. Conclusiones: Se recomienda un control adecuado y una vigilancia apropiada del trabajo de parto, hacer un estricto partograma, y una búsqueda activa, de manera que cada mujer embarazada tenga un adecuado control prenatal y reciba apoyo social.

Analysis of the risk factors of delayed neuropsychologic sequelae after acute carbon monoxide poisoning / 中国基层医药

Objective To explore the risk factors for the development of delayed neuropsychologic sequelae (DNS)and to characterize the clinical course following the development of DNS in acute CO poisoning cases. Methods This study included 79 cases of acute CO poisoning,and they were divided into two groups consisting of 13 cases who developed DNS and 66 cases who did not.The generally conditions of the two groups [including age, gender,exposure environment,the time of coma,whether through referral,the severity of disturbance of consciousness, computed tomography(CT)abnormal,first time to see a doctor if hyperbaric oxygen therapy]and laboratory index [carbon oxygen hemoglobin(COHb),WBC,creatine kinase (CK),creatine kinase isoenzyme (CK -MB),lactate dehydrogenase(LDH),hospitalization time,HBO]were analyzed by single factor variance analysis,Chi -square test and Mann Whitney U test.Results Compared with the non DNS group,in the DNS group,JCS score was significantly higher[(200.4 ±107.24)points vs.(94.55 ±52.71 )points,U =8.373,P <0.01 ],CT abnormal skull increased (76.9% vs.6.2%,χ2 =9.548,P <0.01),CK[(5976.33 ±4 371.92)IU /L vs.(2 384.67 ±650.86)IU /L,F =6.877],CK -MB[(51.22 ±33.28)IU /L vs.(23.47 ±15.66)IU /L,F =4.329],LDH[(395.80 ±270.04)IU /L vs.(221.87 ±101.95)IU /L,F =1.012]increased,there were statistically significant differences between the two groups by single factor analysis(all P <0.01 ).The patients with DNS had longer hospitalized time [(283.27 ± 251.08)d vs.(37.93 ±37.18)d,F =2.283]and HBO time[(51.62 ±16.69)d vs.(7.70 ±5.38)d,F =6.428], there were statistically significant differences between the two groups by single factor analysis (all P <0.01 ). Conclusion In patients with the characteristics identified in this study,administration of HBO therapy should be proactively considered after informing their family at initial stage,thus to decrease the risk of developing DNS.

Hypoxia preconditioning may protect focal cerebral ischemia in rats by downregulation of glycogen synthase kinase 3β, phosphorylated signal transducer and activator of transcription 3 / 国际脑血管病杂志

Objective To investigate the roles of phosphorylated glycogen synthase kinase 3β (pGSK3β) and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) in hypoxic preconditioning-induced neuroprotection against ischemic brain injury in rats.Methods Sixty SD rats were randomly divided into a sham operation group,a cerebral ischemia group,and a hypoxia preconditioning group (n =20 in each group).A model of middle cerebral artery occlusion (MCAO) was induced by the modified suture method.Before the preparation of MCAO model,the rats in the hypoxia preconditioning group were put into a hypobaric oxygen chamber at a simulated altitude of 5 000 m (pressure:0.53 × 105 kPa;partial pressure of oxygen:81 mmHg;1 mmHg =0.133 kPa),3 h a day for 5 days.At 24 h after MCAO modeling,the rats were subjected to neurobehavioral score (n =6) and cerebral infarction volume measurement (n =6).Immunohistochemical staining was used to detect the expression levels of neuronal nuclei (NeuN) and pGSK3β (Ser9) (n=7).Western blot was used to detect the expression levels of pGSK3 β (Ser9) and pSTAT3 (Tyr705) in the ischemic cortex (n =7).Results The neurological deficit score (1.833 ±0.408 vs.2.667 ± 0.516;t =3.101,P=0.011) and cerebral infarction volume (18.137％ ± 0.801％ vs.24.125％ ± 0.694％;t =13.840,P＜ 0.001) in the hypoxia preconditioning group were significantly lower or smaller than those in the cerebral ischemia group.Immunohistochemical staining showed that the numbers of NeuN positive cells in the cerebral ischemia group and the hypoxia preconditioning group were significantly less than that in the sham operation group (48.000 ± 1.414/high power field [HPF],124.833 ± 3.061/HPF,and 213.500 ± 2.429/HPF;F =7 150.550,P ＜ 0.001),the hypoxia preconditioning group was significantly more than the ischemia group (P ＜0.001);the numbers of pSTAT3 positive cells in the cerebral ischemia group and the hypoxia preconditioning group were significantly higher than that in the sham operation group (57.667 ± 1.366/HPF,29.167 ± 1.941/HPF and 3.500 ± 1.049/HPF;F =1 962.649,P ＜0.001),and the hypoxia preconditioning group was significantly less than the ischemia group (P ＜0.001).Western blot analysis showed that the expression levels of ischemic cortical pGSK3β and pSTAT3 in the cerebral ischemia group and the hypoxia preconditioning group were significantly higher than those of the sham operation group (pGSK3 β:2.336 ± 0.102,0.876 ± 0.196 and 0.440 ± 0.012;F =1 610.826,P ＜ 0.001;pSTAT3:8.368± 0.230,4.883± 0.123 and 0.595± 0.138;F=4018.051,P＜0.001),the hypoxia preconditioning group were significantly lower than the ischemia group (all P ＜0.001).Conclusions Hypoxia preconditioning has neuroprotective effect for ischemic brain injury in rats.It may be associated with the down-regulation of the expressions of pGSK3 and pSTAT3.

Effect of ketamine on mitochondrial function of rat neurons subjected to anoxia / 中华麻醉学杂志

Objective To investigate the effect of ketamine on the mitochondrial function of rat neurons subjected to anoxia. Methods Primarily cultured rat hippocampal neurons were seeded in culture dishes (35 mm in diameter) at the density of 5×105-1×106 cells∕ml, and divided into 3 groups (n=11 each) using a random number table: control group, anoxia group and ketamine group. The neurons were exposed to 90% N2 plus 10% CO2 50 ml∕min for 5 min in anoxia group. In ketamine group, ketamine was added to the culture medium with the final concentration of 20 μmol∕L at 1 h before anoxia, and then the neurons were exposed to 90% N2 plus 10% CO2 50 ml∕min for 5 min. After the end of treatment in each group, the dead neurons were detected using trypan blue staining, the ATP content was determined by ATP bioluminescence assay, and mitochondrial membrane potential was measured by rhodamine 123 staining. Results Compared with control group, the mortality rate of hippocampal neurons was significantly in?creased, and the ATP content and mitochondrial membrane potential were significantly decreased in anoxia group and ketamine group ( P<0.05) . Compared with anoxia group, the mortality rate of hippocampal neu?rons was significantly decreased, and the ATP content and mitochondrial membrane potential were signifi?cantly increased in ketamine group (P<0.05). Conclusion The mechanism by which ketamine amelio?rates anoxia?induced damage to rat neurons is related to improved mitochondrial function.

Neuroprotective body hypothermia among newborns with hypoxic ischemic encephalopathy: three-year experience in a tertiary university hospital. A retrospective observational study / Hipotermia corpórea neuroprotetora em recém-nascidos com encefalopatia hipóxico-isquêmica: três anos de experiência em hospital universitário terciário. Um estudo observacional retrospectivo

CONTEXT AND OBJECTIVE:Neonatal hypoxic-ischemic encephalopathy is associated with high morbidity and mortality. Studies have shown that therapeutic hypothermia decreases neurological sequelae and death. Our aim was therefore to report on a three-year experience of therapeutic hypothermia among asphyxiated newborns.DESIGN AND SETTING:Retrospective study, conducted in a university hospital.METHODS:Thirty-five patients with perinatal asphyxia undergoing body cooling between May 2009 and November 2012 were evaluated.RESULTS:Thirty-nine infants fulfilled the hypothermia protocol criteria. Four newborns were removed from study due to refractory septic shock, non-maintenance of temperature and severe coagulopathy. The median Apgar scores at 1 and 5 minutes were 2 and 5. The main complication was infection, diagnosed in seven mothers (20%) and 14 newborns (40%). Convulsions occurred in 15 infants (43%). Thirty-one patients (88.6%) required mechanical ventilation and 14 of them (45%) were extubated within 24 hours. The duration of mechanical ventilation among the others was 7.7 days. The cooling protocol was started 1.8 hours after birth. All patients showed elevated levels of creatine phosphokinase, creatine phosphokinase- MB and lactate dehydrogenase. There was no severe arrhythmia; one newborn (2.9%) presented controlled coagulopathy. Four patients (11.4%) presented controlled hypotension. Twenty-nine patients (82.9%) underwent cerebral ultrasonography and 10 of them (34.5%) presented white matter hyper-echogenicity. Brain magnetic resonance imaging was performed on 33 infants (94.3%) and 11 of them (33.3%) presented hypoxic-ischemic changes. The hospital stay was 23 days. All newborns were discharged. Two patients (5.8%) needed gastrostomy.CONCLUSION:Hypothermia as therapy for asphyxiated newborns was shown to be safe.

CONTEXTO E OBJETIVO:A encefalopatia hipóxico-isquêmica neonatal apresenta alta morbi-mortalidade. Estudos com hipotermia comprovam diminuição de sequelas neurológicas e morte. Nosso objetivo foi então relatar experiência de três anos da hipotermia terapêutica em recém-nascidos (RN) asfixiados.TIPO DE ESTUDO E LOCAL:Estudo restrospectivo, conduzido em hospital universitário.MÉTODOS:Trinta e cinco pacientes com asfixia perinatal submetidos a resfriamento corporal entre maio de 2009 e novembro de 2012 foram avaliados.RESULTADOS:Trinta e nove RN preencheram os critérios do protocolo de hipotermia. Quatro RN foram excluídos devido a choque séptico refratário, não manutenção da temperatura e coagulopatia grave. A mediana do Apgar de 1 e 5 minutos foi de 2 e 5. A maior complicação foi infecção, diagnosticada em sete mães (20%) e 14 RN (40%). Convulsão ocorreu em 15 RN (43%). 31 pacientes (88,6%) necessitaram da ventilação mecânica e 14 (45%) foram extubados em 24 horas. O tempo de ventilação mecânica dos demais foi de 7,7 dias. O início do resfriamento ocorreu com 1,8 horas de vida. Todos os pacientes apresentaram níveis elevados de creatinofosfoquinase, creatinofosfoquinase-MB e desidrogenase lática. Não se observou arritmia grave; um RN (2,9%) apresentou coagulopatia controlada. Quatro pacientes (11,4%) tiveram hipotensão controlada. Realizou-se ultrassonografia cerebral em 29 pacientes (82,9%), 10 (34,5%) com hiperecogenicidade da substância branca. 33 RN (94,3%) fizeram ressonância magnética cerebral, 11 (33,3%) com alterações hipóxico-isquêmicas. O tempo de internação foi de 23 dias e todos receberam alta. Dois pacientes (5,8%) necessitaram de gastrostomia.CONCLUSÃO:A hipotermia como terapêutica para RN asfixiados demonstrou ser segura.

Cognitive impairment in COPD: a systematic review / Cognitive impairment in COPD: a systematic review

The objectives of this study were to characterize and clarify the relationships between the various cognitive domains affected in COPD patients and the disease itself, as well as to determine the prevalence of impairment in the various cognitive domains in such patients. To that end, we performed a systematic review using the following databases: PubMed, Scopus, and ScienceDirect. We included articles that provided information on cognitive impairment in COPD patients. The review of the findings of the articles showed a significant relationship between COPD and cognitive impairment. The most widely studied cognitive domains are memory and attention. Verbal memory and learning constitute the second most commonly impaired cognitive domain in patients with COPD. The prevalence of impairment in visuospatial memory and intermediate visual memory is 26.9% and 19.2%, respectively. We found that cognitive impairment is associated with the profile of COPD severity and its comorbidities. The articles reviewed demonstrated that there is considerable impairment of the cognitive domains memory and attention in patients with COPD. Future studies should address impairments in different cognitive domains according to the disease stage in patients with COPD.

Os objetivos deste estudo foram caracterizar e esclarecer as relações entre os vários domínios cognitivos afetados em pacientes com DPOC e a doença em si, assim como determinar a prevalência de comprometimentos cognitivos em tais pacientes. Para tanto, foi realizada uma revisão sistemática utilizando as seguintes bases de dados: PubMed, Scopus e ScienceDirect. Os artigos incluídos forneciam informações sobre os comprometimentos cognitivos em pacientes com DPOC. A revisão dos achados de tais artigos mostrou uma relação significativa entre DPOC e comprometimento cognitivo. Os domínios cognitivos mais estudados são a memória e a atenção. Memória verbal e aprendizagem constituem o segundo domínio cognitivo mais comumente prejudicado em pacientes com DPOC. A prevalência de comprometimento da memória visuoespacial e da memória visual intermediária é 26,9% e 19.2%, respectivamente. Observamos que o comprometimento cognitivo está associado ao perfil de gravidade da DPOC e suas comorbidades. A revisão dos artigos demonstrou que há um comprometimento considerável dos domínios memória e atenção em pacientes com DPOC. Investigações futuras devem abordar os comprometimentos em diferentes domínios cognitivos em conformidade com o estágio da doença em pacientes com DPOC.

The effect of hyperbaric oxygen on the expression of hypoxia inducible factor-1alpha in brain tissue after acute organophosphate poisoning / 中华物理医学与康复杂志

Objective To study the expression of hypoxia-inducible factor-1 (HIF-1) in the brain tissue after the brain injury caused by acute organophosphate poisoning,and the interventional effect and mechanism of hyperbaric oxygen (HBO) therapy.Methods Sixty healthy male Sprague-Dawley rats randomly divided into a control group (n=6),a poisoning group (n=18),a routine group (n=18) and an HBO group (n=18) according to a random number table.Acute organophosphate poisoning was induced into all rats except those in the control group.The routine group was given penehyclidine hydrochloride and pralidoxime chloride for once,while the HBO group was provided with HBO therapy immediately on the basis of routine treatment.At 1,3 and 7 hours after acute organophosphate poisoning was induced,six rats were sacrificed at each time point and the blood samples were taken from inferior caval vein to measure the content of Malondialdehyde (MDA).The expression of HIF-1α mRNA in the brain tissue was detected by the quantitative real-time PCR,and that of HIF-1 protein was evaluated by immunohistochemical method.Meanwhile,pathologic changes of the brain tissues were observed using hematoxylin-eosin (HE) staining.Results Compared with the poisoning group,the pathological damage to cerebral tissues lessened in the HBO group.The expression of HIF-1 protein and HIF-1 mRNA of the poisoning and the HBO groups was significantly higher than the control group at 3 different time points.After the HBO treatment,the protein expression of HIF-1 lowered from 226.57 ± 57.49,to 205.91 ± 30.36 and further to 187.67 ± 29.25,while the MDA content decreased from 7.74 ± 0.14,to 7.40 ± 0.13 and later to 6.10 ±0.08,both were significantly lower than those of the poisoning group at all time points,with HIF-1 being 1305.67 ± 167.17,2667.83 ± 367.79 and 1709.24 ± 199.07,along with MDA content being 9.48 ± 0.05,11.56 ± 0.13 and 12.26 ± 0.14,and those in the routine group at the time points of 1 and 3 hour later (P ＜ 0.05).A positive correlation was found between the expression level of HIF-1 mRNA and level of MDA in the serum (r =0.909,P=0.000).Conclusion HIF-1 plays an important role in the development of brain injury caused by acute organophosphate poisoning.The efficacy of hyperbaric oxygen intervention against AOPP-induced brain injury is better than that of the routine treatment and its mechanism may be its antioxidation and inhibition of HIF-1 expression.

Comparação dos efeitos da ressuscitação com Ringer lactato, solução salina hipertônica e terlipressina sobre a perfusão e oxigenação cerebral em modelo experimental de choque hemorrágico

INTRODUÇÃO: A ressuscitação de baixo volume com solução salina hipertônica (SSH) ou terlipressina pode ser uma alternativa à administração de grandes volumes de cristaloides no tratamento do choque hemorrágico. O objetivo deste estudo foi avaliar os efeitos da HHS e terlipressina sobre a perfusão e oxigenação cerebral e investigar os mecanismos cerebrais envolvidos na microcirculação, função mitocondrial, atividade eletrocortical e vias apoptóticas cerebrais durante choque hemorrágico. MÉTODOS: Animais anestesiados com isofluorano foram submetidos ao choque hemorrágico [grupo Hemo; pressão arterial média (PAM) de 40 mmHg por 30 minutos] e tratados com Ringer lactato (RL) (3RL; 3x volume de sangue removido), terlipressina (grupo Terli; bolus) ou SSH (grupo SSH; 4 mL/kg bolus) e comparados ao grupo Sham. Um modelo porcino (n = 56) foi utilizado para avaliação da pressão de perfusão cerebral (PPC) e de oxigênio tecidual (PbtO2), e da expressão cerebral de marcadores teciduais da regulação de água (aquaporina-4), sódio (cotransportador-1 de Na-K-2Cl), estresse oxidativo (substâncias reativas ao ácido tiobarbitúrico e superóxido dismutase dependente de manganês) e apoptose. Um modelo murino (n = 179) foi utilizado para avaliação da microcirculação (fluorescência de FITC-dextrano) e função mitocondrial (potencial redox e de membrana mitocondrial, utilizando-se a fluorescência de flavoproteínas endógenas e do tetrametilrodamina metil éster, respectivamente) no córtex cerebral, utilizando-se a microscopia confocal in vivo, e para avaliação da atividade eletrocortical cerebral, por meio da monitorização do potencial evocado somatossensorial. No modelo murino foram avaliados três grupos adicionais, constituídos pela associação da terlipressina ao RL (1x, 2x ou 3x volume removido). RESULTADOS: No grupo Hemo porcino, houve uma redução significativa da PPC e PbtO2, associada ao aumento na expressão cerebral de marcadores da regulação do transporte de água e sódio,...

INTRODUCTION: Small-volume resuscitation with hypertonic saline solution (HSS) or terlipressin can be an alternative to the administration of large amounts of crystalloids in haemorrhagic shock. The aim of this study was to evaluate the effects of HSS and terlipressin on cerebral perfusion and oxygenation and investigate the cerebral mechanisms associated with microcirculation, mitochondrial function, electrocortical activity and apoptotic pathways during haemorrhagic shock. METHODS: Isoflurane-anaesthetised animals were submitted to haemorrhagic shock [Haemo group; mean arterial pressure (MAP) of 40 mmHg for 30 minutes] and treated with lactated Ringer's solution (LR) (3LR group; 3x volume bled), terlipressin (Terli group; bolus) or HSS (HSS group; bolus 4 mL/kg) and were compared with a Sham group. A porcine model (n = 56) was used to assess the cerebral perfusion pressure (CPP) and tissue oxygenation (PbtO2) and the expression of tissue markers of water (aquaporin-4), sodium (Na-K-2Cl cotransporter-1), oxidative stress (thiobarbituric acid reactive substances and manganese superoxide dismutase) and apoptosis in cerebral samples. A murine model (n = 179) was used to assess microcirculation (FITC-dextran fluorescence) and mitochondrial function (redox and membrane potential, using the fluorescence of endogenous flavoproteins and tetramethylrhodamine methyl ester, respectively) in the cerebral cortex by using in vivo confocal microscopy, and to assess the electrocortical brain activity by monitoring the somatosensory evoked potential. In the murine model, three additional groups were evaluated, which received terlipressin associated to LR (1x, 2x or 3x blood withdrawn). RESULTS: In the porcine Hemo group, there was a significant decrease in the CPP and PbtO2, which were associated to an increased cerebral expression of markers of water and sodium transport...

Neural stem cell transplantation:its actuality and future used for treatment of hypoxic-ischemic encephalopathy / 中国组织工程研究

BACKGROUND:Many studies have showed that neural stem cells therapy is a new strategy for hypoxic-ischemic encephalopathy. OBJECTIVE:To review and analyze the status of research, transplantation strategies and mechanism of neural stem cells therapy for treatment of hypoxic-ischemic encephalopathy. METHODS:A computer-based retrieval was performed in PubMed and CNKI database to search papers published from August 2000 to August 2013 using the key words of“hypoxic-ischemic encephalopathy, neural stem cells”in English and Chinese. The papers with objective-independent and repetitive contents were excluded, and final y 39 papers were included for final analysis. RESULTS AND CONCLUSION:Neural stem celltransplantation can promote recovery of neurological function, which brings new hope to hypoxic-ischemic encephalopathy patients. But the study is at a primary stage and limited in laboratory. There are many critical factors that hinder the clinical transplantation, such as delivery path, transplantation time, single or combined transplantation, mechanisms of action. Application of neural stem cells requires further investigation.

The zebrafish as a model organism for the research of neonatal hypoxia brain injury / 中华实用儿科临床杂志

Many factors,especially perinatal asphyxia,can lead to varying degrees of hypoxia brain injury in fetus or newborns within perinatal period.So far,the mechanisms of neonatal cerebral damage caused by hypoxia during the perinatal period have not been clearly demonstrated,and there have no effective drugs or therapeutic methods to improve hypoxia-induced cerebral damage.This review focuses on the recent progress of zebrafish as a model organism of using in research of hypoxia brain injury,including the anatomic and behavior basis,model making,research strategies and the advantages of neurotrophic drug screening.The application of zebrish in the research of neonatal hypoxic brain injury is promising,and may provide a new tool as research in finding out the therapy strategies of hypoxic-ischemic encephalopathy.

Clinical study of gangliosides combined with hyperbaric oxygen therapy on neonatal ischemic encephalopathy / 中国基层医药

Objective To investigate the therapeutic effect of gangliosides combined with hyperbaric oxygen therapy( HBO) in treatment of neonatal ischemic encephalopathy ( HIE) .Methods 68 patients with HIE were ran-domly divided into 4 groups(n=17):the control group,gangliosides group,HBO group and combined group .The con-trol group received conventional therapy ,gangliosides and HBO group received gangliosides and HBO therapy respec-tively and combined group received both gangliosides and HBO therapy .The therapeutic effects were evaluated 10d and 20d after treatment.Results Compared with the control group ,the total efficiency was significantly increased in the combined group(χ2 =5.885,P<0.05),but not in gangliosides and HBO group .Moreover,all treatment groups significantly elevated the neonatal behavioral neurological assessment (NBNA)in day 10 and 20,and there were signif-icant differences between the combined group and gangliosides or HBO group ( t=3.755,P<0.05;t=3.533,P<0.05).Conclusion The use of gangliosides combined with HBO has synergistic interaction in treatment of HIE , which is worthy of clinical application .

Application of Buyanghuishensan plus hyperbaric oxygen in the treatment of delayed encephalopathy after acute carbon monoxide poisoning / 中国基层医药

Objective To explore the effect of Buyanghuishensan plus hyperbaric oxygen and medicine in the treatment of delayed encephalopathy after acute carbon monoxide poisoning .Methods According to the digital t able,143 patients with delayed encephalopathy after acute carbon monoxide poisoning were randomly divided into two groups .70 patients in the control group were treated by hyperbaric oxygen and medicine ,while 73 patients in the treat-ment group were treated by Buyanghuishensan plus hyperbaric oxygen and medicine .They were treated for three months.After three months,MMSE and ADL were used to determine changes of the patients'neurological function. Results The total effective rate of the treatment group was 97.3%,which was significantly higher than 88.6%in the control group(χ2 =4.84,P<0.05).After treatment for 3 months,the MMES score of the two groups increased signif-icantly (t=3.096,4.725,all P<0.01),and that of the treatment group increased more significantly (t=2.466,P<0.05).After treatment for 3 months,the ADL score of the two groups decreased significantly (t=2.691,3.179,P<0.05 or P<0.01),and that of the treatment group decreased more significantly (t=2.607,P<0.05).Conclusion Buyanghuishensan plus hyperbaric oxygen and medicine can improve neurological function in patients with delayed encephalopathy after acute carbon monoxide poisoning .

Change and significance of serum levels of CRH, NOS and 5-HT in acute carbon monoxide poisoning patients with delayed encephalopathy / 中华全科医师杂志

To explore the change and significance of serum levels of corticotropin releasing hormone (CRH),nitric oxide synthase (NOS) and 5-hydroxytryptamine (5-HT) in the pathogenesis of acute carbon monoxide poisoning delayed encephalopathy (DEACMP).The groups of DEACMP (n =42),acute carbon monoxide poisoning (ACOP) (n =40) and normal control (n =40) were selected.The peripheral blood levels of CRH,NOS and 5-HT were measured for acute and convalescent phases of three groups.Information-memory-concentration test (IMCT),activities of daily living (ADL) and Hasegawa's dementia scale (HDS) were used to evaluate the intelligent state of acute and convalescent phases.When DEACMP and ACOP groups in acute phase were compared with normal control group,the serum levels of CRH and NOS significantly increased while the serum level of 5-HT decreased markedly (P ＜ 0.05).And statistically significant difference existed between DEACMP and ACOP groups (P ＜ 0.05).After treatment,the serum levels of CRH and NOS significantly decreased while the serum level of 5-HT increased markedly in DEACMP and ACOP groups in convalescent phase (P ＜ 0.05).The IMCT and HDS scores of acute phase DEACMP group were significantly lower than those of ACOP group while ADL was significantly higher (P ＜0.05).After treatment,the scores of IMCT and HDS increased and ADL decreased in DEACMP group in convalescence (P ＜ 0.05).CRH was correlated positively with NOS (P ＜ 0.05) and negatively with 5-HT (P ＜ 0.05).Hypothalamic-pituitary-adrenal cortical axis,NO-NOS system and the presence of 5-HT may be related with the pathogenesis of DEACMP.