Mechanisms of brain damage caused by inorganic fluoride using proteomics-based techniques / 环境与职业医学

Background Chronic excessive exposure to fluoride can cause damage to the central nervous system and a certain degree of learning and memory impairment. However, the associated mechanism is not yet clear and further exploration is needed. Objective Using 4D unlabelled quantitative proteomics techniques to explore differentially expressed proteins and their potential mechanisms of action in chronic excessive fluoride exposure induced brain injury. Methods Twenty-four SPF-grade adult SD rats, half male and half male, were selected and divided into a control group and a fluoride group by random number table method, with 12 rats in each group. Among them, the control group drank tap water (fluorine content<1 mg·L−1), the fluoride group drank sodium fluoride solution (fluorine content 10 mg·L−1), and both groups were fed with ordinary mouse feed (fluoride content<0.6 mg·kg−1). After 180 d of feeding, the SD rats were weighed, and then part of the brain tissue was sampled for pathological examination by hematoxylin-eosin (HE) staining and Nissl staining. The rest of the brain tissue was frozen and stored at −80 ℃. Three brain tissue samples from each group were randomly selected for proteomics detection. Differentially expressed proteins were screened and subcellular localization analysis was performed, followed by Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, cluster analysis, and protein-protein interaction analysis. Finally, Western blotting was used to detect the expression levels of key proteins extracted from the brain tissue samples. Results After 180 d of feeding, the average weight of the rats in the fluoride group was significantly lower than that in the control group (P<0.05). The brain tissue stained with HE showed no significant morphological changes in the cerebral cortex of the fluoride treated rats, and neuron loss, irregular arrangement of neurons, eosinophilic changes, and cell body pyknosis were observed in the hippocampus. The Nissl staining results showed that the staining of neurons in the cerebral cortex and hippocampus of rats exposed to fluoride decreased (Nissl bodies decreased). The proteomics results showed that a total of 6927 proteins were identified. After screening, 206 differentially expressed proteins were obtained between the control group and the fluoride group, including 96 up-regulated proteins and 110 down-regulated proteins. The differential proteins were mainly located in cytoplasm (30.6%), nucleus (27.2%), mitochondria (13.6%), plasma membrane (13.6%), and extracellular domain (11.7%). The GO analysis results showed that differentially expressed proteins mainly participated in biological processes such as iron ion transport, regulation of dopamine neuron differentiation, and negative regulation of respiratory burst in inflammatory response, exercised molecular functions such as ferrous binding, iron oxidase activity, and cytokine activity, and were located in the smooth endoplasmic reticulum membrane, fixed components of the membrane, chloride channel complexes, and other cellular components. The KEGG significantly enriched pathways included biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments. The results of differential protein-protein interaction analysis showed that the highest connectivity was found in glucose-6-phosphate isomerase (Gpi). The expression level of Gpi in the brain tissue of the rats in the fluoride group was lower than that in the control group by Western blotting (P<0.05). Conclusion Multiple differentially expressed proteins are present in the brain tissue of rats with chronic fluorosis, and their functions are related to biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments; Gpi may be involved in cerebral neurological damage caused by chronic overdose fluoride exposure.

Effect of mobile phone radiofrequency electromagnetic radiations on oxidative stress and feeding behaviour in Sprague Dawley (SD) rats

Objectives: Radiofrequency electromagnetic radiation (RF-EMR) from mobile phones is known to produce a stress response because of its effect on hypothalamus. Mobile phones have become an integral part of our lives with increasing usage not only in terms of number of users but also increase in talk time. The present study aimed to study the effect of mobile phone radiofrequency electromagnetic radiations on oxidative stress and feeding behaviour assessment in Sprague Dawley (SD) rats. Materials and Methods: Twelve male SD rats of 10–12 weeks old, weighing 180–220 g, were housed and allowed to acclimatise in a room with 12:12 h light-dark cycle with ad libitum amount of food and reverse osmosis (RO) water before the start of the study. Then, rats were divided into control and RF-EMR exposed groups, and everyday feed intake and body weight were measured. At the end of the study period, blood sample was collected through retro orbital puncture for biochemical investigations. Results: The present study showed significant increase in malondialdehyde and serum corticosterone levels and decrease feeding behaviour in rats exposed to RF-EMR in rats exposed to RF-EMR. Conclusion: This study proves that mobile RF-EMR causes oxidative stress and oxidative damage leading to decreased feeding behaviour in SD rats.

The correlation between the severity of hypoxic-ischemic brain damage in neonatal rats and subsequent abnormal neurobehavior / 中国新生儿科杂志

Objective:To assess the severity of hypoxic-ischemic brain damage (HIBD) in neonatal rats and predict the occurrence of subsequent neurobehavioral abnormalities after brain injury by scoring and magnetic resonance imaging (MRI).Methods:7-day-old of 60 Sprague-Dawley (SD) rats were randomly divided into control group (14 rats), sham operation group (14 rats) and HIBD model group (32 rats). HIBD model was established by right common carotid artery dissection with Rice-Vannucci method and hypoxia. Within 24 h after modeling, the rats in the model group were evaluated by general condition score and Longa score, and the surviving rats with moderate and severe HIBD were selected for the experiment. 24 h after modeling, 5 rats of the model group were randomly selected for 2,3,5-triphenyltetrazole chloride staining to verify cerebral infarction. 1 week after modeling, 6 rats from each group were randomly selected for hematoxylin-eosin staining to observe HIBD brain injury. 4 weeks after modeling, 4 rats were randomly selected from the control group and the sham operation group, and 8 rats from the remaining model group were used to evaluate the volume of brain damage by MRI. 5-6 weeks after modeling, the remaining 8 rats from each group were subjected to the Cylinder test, and at 13 weeks, they underwent the Morris water maze test to evaluate their neurobehavior.Results:In HIBD model group, 19 rats with moderate to severe HIBD were selected from 32 rats. 24 h after modeling, cerebral infarction was verified in all rats, indicating moderate to severe HIBD. Brain tissue pathology observed 1 week after modeling revealed predominantly gray matter brain damage. MRI showed that 7 out of 8 rats had moderate to severe HIBD. Compared to the control and sham operation groups, the model group exhibited a significant decrease in the usage rate of the left forelimb in the Cylinder test at 5-6 weeks after modeling ( P<0.05), and the latency period in Morris water maze test was significantly prolonged at 13 weeks after modeling ( P<0.05), and the times of crossing platform quadrant were significantly reduced ( P<0.05). There was no significant difference in the right brain injury volume between 24 h and 4 weeks model group ( P>0.05). The brain injury volume in model group was negatively correlated with the usage rate of left forelimb in cylinder test at 5-6 weeks and the times of crossing platform quadrant in Morris water maze test at 13 weeks ( P<0.05), and positively correlated with latency period in Morris water maze test at 13 weeks ( P<0.05). Conclusions:Within 24 h of HIBD modeling, the severity of brain injury can be preliminarily predicted by general condition score and Longa score. 4 weeks after modeling, in the chronic phase of brain injury, MRI was proved to be an excellent predictor for mid-term and long-term neurobehavioral abnormalities in HIBD rats.

Transplanting bone marrow mesenchymal stem cells can induce neural regeneration / 中华物理医学与康复杂志

Objective:To observe any effect of transplanting bone marrow mesenchymal stem cells (BMSCs) on microglia and neuron expression in newborn mice with hypoxic-ischemic brain damage (HIBD).Methods:Sixty 10-day-old C57BL/6 mice were randomly divided into a sham operation group, a hypoxic-ischemia group, a placebo group and a stem cell group, each of 15. The hypoxia-ischemia model was induced in the hypoxia-ischemia, placebo and stem cell groups, while the sham operation group was sutured after the neck incision. After successful modeling, the rats in the stem cell group were injected with BMSCs into the bregma while those in the placebo group received phosphate buffered saline. Seven days later, brain tissue was resected and its structure was observed using transmission electron microscopy. Immunofluorescence staining was performed to observe the expression of microglia and neurons in the left cerebral cortex.Results:Seven days after stem cell transplantation, the neuron morphology had improved and nerve fiber swelling was relieved in the stem cell group. The average expression of neurons was significantly greater in the stem cell group compared with the hypoxic-ischemia and placebo groups, while the expression of microglia was significantly lower.Conclusions:Bone marrow mesenchymal stem cells may induce neuron regeneration and reduce inflammatory response by inhibiting the expression of microglia, at least in neonatal rats modeling hypoxic-ischemic brain injury.

Alteraciones psicosociales y dimensiones de la calidad de vida en pacientes con daño cerebral adquirido

RESUMEN El objetivo del estudio estuvo dirigido a establecer los indicadores de alteraciones psicosociales y las dimensiones que interfieren en la calidad de vida, según el paciente con daño cerebral adquirido, sus familiares y los especialistas de asistencia, pertenecientes al Consejo Popular San Juan de Dios. Se realizó un estudio mixto cuanticualitativo en el período comprendido entre mayo de 2018 y mayo de 2020, el que se extiende hasta hoy, atendiendo a los resultados que se han incorporado a la práctica médica sobre la base de la implementación de un proyecto de investigación que se ejecutó a partir de la colaboración entre el Centro de Desarrollo de las Ciencias Sociales y Humanísticas en Salud y el Hospital Universitario Manuel Ascunce Domenech, de Camagüey. La muestra la constituyeron 30 pacientes y sus familiares, pertenecientes a los consultorios de mayor prevalencia en los casos objeto de estudio. Para el desarrollo de la investigación se emplearon métodos empíricos, teóricos y matemático-estadísticos y se aplicó la escala de la calidad de vida del paciente con daño cerebral (CAVIDACE), dirigida a la familia. Como principales resultados se determinó que las principales funciones psíquicas superiores que mostraron alteraciones fueron los procesos de atención y memoria. Se apreciaron en la mayoría de los pacientes alteraciones emocionales, conductuales, en la autonomía funcional y en la integración social. Las dimensiones de la calidad de vida que evidencian más alteraciones fueron la inserción social, el bienestar emocional y físico, el desarrollo personal y las relaciones interpersonales. De acuerdo con el percentil de la escala se evidenciaron resultados de calidad de vida baja en la mayoría de los pacientes, posterior al daño cerebral adquirido.

ABSTRACT The general objective of the study was aimed at establishing the indicators of psychosocial alterations and the dimensions that interfere with quality of life, according to the patient with acquired brain injury, their relatives and assistance specialists, belonging to the San Juan de Dios Popular Council. A mixed quantitative-qualitative study was carried out in the period between May 2018 and May 2020, which extends until today, based on the results that have been incorporated into medical practice based on the implementation of a research project that It was executed from the collaboration between the Center for the Development of Social and Humanistic Sciences in Health and the Manuel Ascunce Domenech University Hospital, in Camagüey. The sample was made up of 30 patients and their relatives, belonging to the most prevalent clinics in the cases under study. For the development of the research, empirical, theoretical and mathematical-statistical methods were used, and the scale of the quality of life of the patient with brain damage (CAVIDACE), aimed at the family, was applied. As main results, it was determined that the main superior psychic functions that showed alterations were: attention and memory processes. Emotional, behavioral, functional autonomy and social integration alterations were observed in most of the patients. The dimensions of quality of life that showed more alterations were: social insertion, emotional and physical well-being, personal development and interpersonal relationships. According to the percentile of the scale, results of low quality of life were evidenced in most of the patients, after to the acquired cerebral damage.

Ameliorative effect of scutellarin on acute alcohol brain injury in mice / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Drinking culture has high significance in both China and the world, whether in the entertainment sector or in social occasions; according to the World Health Organization's 2018 Global Alcohol and Health Report, about 3 million people died from excessive drinking in 2016, accounting for 5.3% of the total global deaths that year. Oxidative stress and inflammation are the most common pathological phenomena caused by alcohol abuse (Snyder et al., 2017). Scutellarin, a kind of flavonoid, is one of the main active ingredients extracted from breviscapine. It exerts anti-inflammatory, antioxidant, and vasodilation effects, and has been used to treat cardiovascular diseases and alcoholic liver injury. Although scutellarin can effectively alleviate multi-target organ injury induced by different forms of stimulation, its protective effect on alcoholic brain injury has not been well-defined. Therefore, the present study established an acute alcohol mice brain injury model to explore the effect of scutellarin on acute alcoholic brain injury. The study was carried out based on the targets of oxidative stress and inflammation, which is of great significance for the targeted therapy of clinical alcohol diseases.

Complementarity of pain assessment instruments in children with central nervous system impairment / Complementariedad de instrumentos de medición del dolor en niños con compromiso del sistema nervioso central / Complementaridade de instrumentos de mensuração de dor em crianças com comprometimento do sistema nervoso central

ABSTRACT Objective: To evaluate the complementarity of the revised Face, Legs, Activity, Cry, Consolability scale and of the Inventory of Pain Behavior in Neurological Disability for the assessment of pain in children with severe neurological impairment. Method: Cross-sectional study conducted in pediatric units of a university hospital in the southern region of Brazil. The sample consisted of 26 children with severe neurological impairment, hospitalized from January to August 2019, and their caregivers. The data were analyzed by descriptive statistics; Kappa Coefficient, Fisher's Exact Test and Spearman's Coefficient were used (p≤0,05). Results: Most children primary diagnosis was cerebral palsy (80.8%). Pain was present in 50.0% of children with the application of the scale and in 34.6% with that of the inventory. Considering the two instruments, there was good agreement (84.6%) between respondents (k=0.692; 95% CI 0.437-0.967; p=0.000). Conclusion: The instruments can be used complementarily to assess pain in children with this profile.

RESUMEN Objetivo: Evaluar la complementariedad de la Escala revised Faces, Legs, Activity, Cry and Consolability y del Inventario de Comportamientos del Dolor en la Deficiencia Neurológica para la medición del dolor en los niños con severo compromiso neurológico. Método: Estudio transversal, realizado en las unidades pediátricas de un hospital universitario de la región sur de Brasil. Muestra de 26 niños con severo compromiso neurológico, internados desde enero a agosto de 2019, y sus cuidadores. Datos analizados por estadística descriptiva; se utilizó el coeficiente Kappa, la Prueba Exacta de Fisher y la Coeficiente de Spearman (p≤0,05). Resultados: La mayoría de los niños tenía un diagnóstico primario de parálisis cerebral (80,8%). La puntuación indicó presencia de dolor en 50% de los niños por la aplicación de la escala, y en 34,6%, por el inventario. Considerando los dos instrumentos, hubo una buena concordancia (84,6%) entre los encuestados (k=0, 692; IC 95% 0,437-0,967; p=0,000). Conclusión: Los instrumentos se puede utilizar de forma complementaria para evaluar el dolor en este perfil de niños.

RESUMO Objetivo: Avaliar a complementaridade da Escala revised Faces, Legs, Activity, Cry and Consolability e do Inventário de Comportamentos da Dor na Deficiência Neurológica para mensuração da dor em crianças com comprometimento neurológico severo. Método: Estudo transversal, realizado em unidades pediátricas de um hospital universitário da região Sul do Brasil. Amostra de 26 crianças com comprometimento neurológico severo, internadas de janeiro a agosto de 2019, e seus cuidadores. Dados analisados por estatística descritiva; Coeficiente de Kappa, Teste Exato de Fisher e Coeficiente de Spearman foram utilizados (p≤0,05). Resultados: Maioria das crianças apresentou diagnóstico primário de paralisia cerebral (80,8%). Presença de dor foi pontuada em 50% das crianças com a aplicação da escala e, em 34,6%, com inventário. Considerando os dois instrumentos, houve boa concordância (84,6%) entre os respondentes (k=0,692; IC 95% 0,437-0,967;p=0,000). Conclusão: Os instrumentos podem ser utilizados de forma complementar na avaliação da dor neste perfil de crianças.

Leigh syndrome in an infant: autopsy and histopathology findings

Leigh syndrome is an inherited neurodegenerative disorder of infancy that typically manifests between 3 and 12 months of age. The common neurological manifestations are developmental delay or regression, progressive cognitive decline, dystonia, ataxia, brainstem dysfunction, epileptic seizures, and respiratory dysfunction. Although the disorder is clinically and genetically heterogeneous, the histopathological and radiological features characteristically show focal and bilaterally symmetrical, necrotic lesions in the basal ganglia and brainstem. The syndrome has a characteristic histopathological signature that helps in clinching the diagnosis. We discuss these unique findings on autopsy and radiology in a young infant who succumbed to a subacute, progressive neurological illness suggestive of Leigh syndrome. Our case highlights that Leigh syndrome should be considered in the differential diagnosis of infantile-onset, subacute neuroregression with dystonia and seizures, a high anion gap metabolic acidosis, normal ketones, elevated lactates in blood, brain, and urine, and bilateral basal ganglia involvement.

Long-term Behavioral Disorder after Hypoxic Ischemic Brain Damage in Newborn Mice / 中国康复理论与实践

Objective:To observe the long-term behavioral changes in movement, emotion, and learning and memory of newborn mice with hypoxic ischemic brain damage (HIBD). Methods:A total of 50 ten-day old newborn C57BL/6 mice were divided into control group (n = 20) and HIBD group (n = 30). The left common carotid artery was ligated in HIBD group and stayed in anoxic chamber for 45 minutes. All the mice were tested with suspension test, light/dark box test, elevated plus maze test, object recognition test and Y maze test two months after surgery. Results:There were 19 mice modeled successfully. Compared with the control group, the suspension test scores decreased (t = 2.785, P < 0.05); the time of latency of light/dark box test increased (t = -4.320, P < 0.001), the time and frequency in light box decreased (t > 2.603, P < 0.05); the time in open arm decreased (t = 4.576, P < 0.001) and the time in close arm increased (t = -3.287, P < 0.01) for the elevated plus maze test; the time nearing old object increased (t = -2.116, P < 0.05) and object recognition index decreased (t = 2.823, P < 0.05) for object recognition test; the time in the initial and novel arms decreased (t > 2.191, P < 0.05) for Y maze test in HIBD group. Conclusion:The long-term disorders of behavior may include disabilities of motor, learning and memory, and disorder of anxiety, in newborn mice with HIBD.

El estrés postraumático como precursor de daños en salud mental y cognición en víctimas de violencia / Post-Traumatic Stress as a Precursor of Mental Health Damage and Cognitive Impairment in Victims of Violence

Resumen Este artículo tiene como objetivo mostrar como la violencia es un acto dañino a nivel social que genera detrimento en la salud mental y deterioro cognitivo. Se realizó una revisión sistemática basada en una estrategia de búsqueda siguiendo los lineamientos prisma. Estos artículos estuvieron relacionados con la psicopatología, la violencia, y los daños cognitivos en personas víctimas de la violencia. Se sistematizaron 50 artículos en total de las bases de datos PubMed, ScienceDirect, PsicoDoc, Proquest, y Google Académico. Las palabras claves fueron: salud mental*violencia, psicopatología*violencia, daño cognitivo*violencia, mental health*violence, cognitive imparment*violence, war*mental health, traumatic stres*brain injury, entre los años 2008-2018. Los resultados indican que los daños en salud mental más frecuentes derivados de actos violentos son el trastorno por estrés postraumático (tept) que genera daños cognitivos en atención, memoria de trabajo, y aprendizaje. Estas son funciones cognitivas necesarias para un desempeño óptimo de la vida diaria. Además el teptdesencadena depresión, ansiedad, y otras alteraciones psiquiátricas como el trastorno afectivo bipolar, o la esquizofrenia.

Abstract This article aims to demonstrate how violence is a socially damaging act that generates mental health detriment and cognitive impairment. A systematic review of articles was carried out based on the prismaguidelines. Studies found were related to psychopathology, violence, and cognitive impairment in victims of violence. A total of 50 articles, dated from 2008 to 2018, were systematized in databases such as PubMed, ScienceDirect, PsicoDoc, Proquest, and Google Scholar. The keywords were health*violence, psychopathology*violence, cognitive impairment*violence, mental health*violence, cognitive impairment*violence, war*mental health, traumatic stress*brain injury. The results indicate that the most frequent mental health damage derived from violent acts is the post-traumatic stress disorder (ptsd) that causes cognitive impairment in attention, working memory, and learning, which are necessary cognitive functions for optimal performance in daily life. Besides, ptsdtriggers disorders such as depression, anxiety, and other psychiatric diseases such as bipolar affective disorder or schizophrenia.

Análisis neuropsicológico de un caso con anosognosia / Neuropsychological analysis of a case with anosognosia

Resumen La anosognosia es un trastorno neuropsicológico que genera en el paciente una incapacidad para tener un estado de conciencia pleno sobre su enfermedad o déficit, producto de una injuria cerebral. En este artículo reportamos el análisis de un caso que producto de un traumatismo craneoencefálico presentó esta alteración cerebral. El análisis neuropsicológico inicia con la descripción clínica del caso, su estado premórbido, el relato familiar del estado actual y un análisis neuropsicológico que sustenta la hipótesis diagnóstica de anosognosia. Se discute el caso presentado en base a la necesidad de realizar diagnósticos precisos y proponer programas de rehabilitación neuropsicológica para que los pacientes con anosognosia sufran el menor impacto posible en las actividades de su vida diaria producto del trastorno cerebral adquirido.

Anosognosia is a neuropsychological disorder that generates in the patient an inability to have a state of full awareness about their disease or deficit due to brain injury. In this article we report the analysis of a case that, due to a head injury, presented this brain disorder. The neuropsychological analysis begins with the clinical description of the case, its premorbid status, the family report of the current state and a neuropsychological analysis of the symptoms presented that support the diagnostic hypothesis of anosognosia. The case presented is discussed based on the need to make accurate diagnoses and propose neuropsychological rehabilitation programs so that patients with anosognosia suffer the least possible impact on the activities of their daily lives as a result of acquired brain disorder.

Integración de las tecnologías de la información y la comunicación en la intervención neuropsicológica / Integration of information and communication technologies into neuropsychological interventions

El objetivo del presente artículo fue ofrecer una visión actualizada del uso de las tecnologías de la información y la comunicación en la intervención neuropsicológica de pacientes con daño cerebral. Para esto se realizó la revisión de la literatura publicada sin límite de fecha y hasta junio del año 2019, en las bases de datos MedLine, Embase, Hinari, Lilacs y SciELO, y se consideró la experiencia profesional de los autores en el tema. Las principales tecnologías de la información y la comunicación que se utilizan en la actualidad en la evaluación neuropsicológica y la rehabilitación de los procesos cognitivos en esta población son los softwares, la telerrehabilitación, la realidad virtual, los teléfonos inteligentes, las apps móviles y los videojuegos. Estas tecnologías se han empleado en el tratamiento de diferentes funciones cognitivas (atención, memoria, funciones ejecutivas, habilidades visoespaciales, lenguaje, entre otros) y en diferentes tipos de patologías (traumatismos craneoencefálicos, demencias, ictus, epilepsia, adultos mayores, etcétera). Uno de los retos para el futuro será la creación de tecnologías que demuestren su eficacia en la reintegración de estos pacientes a su vida cotidiana. En Cuba diversas instituciones han integrado la información y la comunicación a la investigación neuropsicológica y han confirmado su utilidad clínica(AU)

The purpose of the study was to provide an updated view of the use of information and communication technologies in the neuropsychological intervention of brain damage patients. To achieve such an end, a review was conducted of the literature published on any date prior to June 2019 in the databases MEDLINE, EMBASE, HINARI, LILACS and SciELO. The authors' professional experience in the subject was taken into account. The main information and communication technologies in current use for the neuropsychological evaluation and rehabilitation of cognitive processes in this population are software, telerehabilitation, virtual reality, smart phones, mobile apps and video games. These technologies have been used to treat a variety of cognitive functions (attention, memory, executive functions, visual-spatial abilities and language, among others) and conditions (traumatic brain injury, dementias, stroke, epilepsy, elderly patients, etcetera). One of the challenges to be faced in the future will be the creation of technologies proving their effectiveness in the reincorporation of these patients to their daily activities. Several Cuban institutions have integrated information and communication technologies into neuropsychological research, confirming their clinical usefulness(AU)

Prevalence and Risk Factors of Urolithiasis in Children with Cerebral Palsy

Introduction:Cerebral palsy (CP)is due to damage occurring to the developing brain. This damage can occur during pregnancy, delivery, the first month of life, or less commonly in early childhood. Cerebral palsy is one of the most common causes of physical disability in childhood. Rates of cerebral palsy appear to be similar in both the developing and developed world. The overall CP morbidity rate will automatically increase unless a substantially improved outcome in survivors can be achieved. Children with CP are predisposed to many complications including renal stones.Aim of the Study:The aim of this study was detection of prevalence and risk factors of urolithiasis in children with cerebral palsy.Subjects and Methods:This cross sectional case control study was conducted on forty children suffering from cerebral palsy who were attending the Pediatric Neurology Unit of Tanta University Hospital through the period from March 2018 to March 2019. Fortyage and sex matched children were taken as a control group. Inclusion Criteria:Children suffering from different types of cerebral palsy at any age. Exclusion Criteria:Children whose parents refuse to participate in the study, children receiving drugsthat can cause renal stones.A-Hematological Investigations:Total serum calcium, serum uric acid, serum creatinine.B-Urinary:Complete urine analysis, urine culture,and urinary chemistry. C -Imaging Study:Plain X-ray of abdomen. Pelvic and renal ultrasonography.Results:Renal stone were detected in 12.5% of children with CP. Urinary tract infection, immobilization, hypercalcemia, hypercalciuria and hyperuricemia were the risk factors detected in this study. Conclusion:Children with CP are liableto develop renal stones more than normal children

Advances in Neuropathologic Research of Hypoglycemic Brain Damage Caused by Insulin Overdose / 法医学杂志

The number of death from insulin overdose, including accidental poisoning, suicide and homicide, is increasing these years. The forensic diagnosis of death from insulin overdose is a tough task. Glucose is the main energy source of the brain. Therefore, hypoglycemic brain damage is considered to be the main reason of death from insulin overdose. Recently, research of hypoglycemic brain damage caused by insulin overdose is gradually being paid attention in the field of forensic medicine. This paper summarizes the neuropathologic changes, pathophysiologic process and potential neural molecular markers of hypoglycemic brain damage caused by insulin overdose in terms of forensic neuropathology, providing reference for the research and practice in forensic medicine related fields.

Acupuncture improves locomotor activity and learning-memory ability by improving hippocampal cellular autophagy in rats with fetal intrauterine distress / 针刺研究

OBJECTIVE: To investigate the effect of acupuncture stimulation of head acupoints "Jin San Zhen" (JIN's Three Acupuncture Needles Therapy) on behavior reactions, hippocampal neuronal autophagy and expression of autophagy associated proteins (Beclin-1 and light chain 3 Ⅱ/Ⅰ [LC 3 Ⅱ/Ⅰ]) in rats with hypoxic-ischemic brain damage (HIBD) due to fetal intrauterine distress, so as to reveal its underlying mechanisms in improving neonatal HIBD. METHODS: Pregnant SD rats were used in the present study. The HIBD model was established by delayed caesarean delivery and bilateral uterine arteries clipping for 10 minutes. The HIBD rats were randomly divided into model group and acupuncture groups (n＝9 rats in each group). The other 9 rats delivered naturally were used as the normal control group. On day 14 after delivery, the neonatal rats in the acupuncture group received acupuncture stimulation of head acupoints ("Nao San Zhen""Nie San Zhen" and "Zhi San Zhen") by twirling each needle leftward and rightward for 10 times, once a day for 14 d. The open field test and Morris water maze test were used to determine the locomotive activity and spatial learning-memory ability, respectively. The ultrastructure and autophagosomes in the hippocampal neurons were observed by transmission electron microscope. The contents and expression levels of Beclin-1 and LC3 Ⅱ/Ⅰ in the hippocampus tissues were detected by flow cytometry and Western blot, separately. RESULTS: Compared with the normal control group, the time to go out of the central region of open field test, and the escape latency and duration of first platform-quadrant-crossing of spatial exploration of Morris water maze tests were significantly increased (P<0.01，P<0.05，P<0.001), and the total distance and number of activities in the central region, and the target quadrant resistance time and number of platform-cros-sing remarkably decreased in the model group (P<0.01, P<0.05), suggesting a decline of both locomotor activity and learning-memory ability after modeling. The expression level (%) of Beclin-1 protein and ratio of LC3 Ⅱ/Ⅰ proteins were considerably increased in the model group (P<0.01). Following acupuncture interventions, the locomotor activity and spatial learning-memory ability were obviously increased (P<0.05，P<0.01，P<0.001), and the expression of Beclin-1 protein and ratio of LC3 Ⅱ/Ⅰ were further up-regulated relevant to the model group (P<0.001). Moreover, ultrastructural observation showed serrated change of nuclear membrane and widened perinuclear space, vacuolization in the mitochondria, dilation of endoplasmic reticulum and increase of autophagosomes in the hippocampal neurons in the model group. These situations were relatively milder in the acupuncture group. CONCLUSION: Acupuncture of head acupoints of "JIN San Zhen" may increase locomotor activity and learning-memory abi-lity in rats with HIBD due to fetal intrauterine anoxia, which is closely with its effect in promoting hippocampal neuronal autophagy via up-regulating the expression of Beclin-1 and LC3 Ⅱ/Ⅰ.

VP1-binding protein glucose-regulated protein 78 as an important mediator for enterovirus 71 infecting human brain microvascular endothelial cells

Purpose: Enterovirus 71 (EV71) is one of the main pathogens causing hand, foot and mouth disease, which could even induce severe brain damage in some patients. As the underlying mechanism of the invasion and replication process still remains largely unknown, we investigated the role of candidate proteins expressed during EV71 invasion in human brain microvascular endothelial cells (HBMECs) to delineate the pathophysiological mechanism of EV-71 infection. Materials and Methods: Ninety-one candidate EV71-associated proteins which could bind the major capsid protein (viral protein 1 [VP1]) of EV71 on the HBMEC were identified by applying an analysis of glutathione-S-transferase pull-down coupling with liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS). Seventy-eight kDa glucose-regulated protein 78 (GRP78) binding to the VP1 protein was further validated by co-immunoprecipitation, immunofluorescence and western blot analysis. To explore the role of GRP78 in EV71 infection, GRP78 was knocked down and overexpressed in HBMEC and was verified by TCID50 assay. Results: LC-ESI-MS/MS-identified 91 proteins were subjected to gene ontology analysis, and on molecular and biological function analysis revealed GRP78 act as an important binding protein in mediating EV71 infection. In addition, immunofluorescence demonstrated the co-localisation of GRP78 and VP1 in cytoplasm of the infected HBMEC. The TCID50 assay showed that knockdown of GRP78 could attenuate the replication capacity of EV71 in HBMEC, and the overexpression could increase the virus titre in HBEMC at 24 h post-infection suggesting that GRP78 was associated with the replication capacity of EV71 in HBMEC. Conclusion: These findings provided evidence that GRP78 plays an important role during the progression of EV71 infection as a mediator in HBMEC.

¿El licopeno puede eliminar los efectos perjudiciales de la hiperoxia en los cerebros inmaduros? / Can lycopene eliminate the harmful effects of hyperoxia in an immature brain?

Objetivos: Al ser un antioxidante, el licopeno protege a las células contra el daño causado por los radicales libres, fortalece los enlaces intercelulares y mejora el metabolismo celular. Este estudio analiza los efectos del licopeno sobre los trastornos neurodegenerativos por hiperoxia en ratas recién nacidas a término. Métodos: Estas ratas se dividieron en cuatro grupos: grupo 1 de referencia con normoxia, grupo 2 con normoxia + licopeno, grupo 3 de referencia con hiperoxia y grupo 4 con hiperoxia + licopeno. Los grupos 1 y 2 se supervisaron en condiciones de aire ambiental, y los grupos 3 y 4 se supervisaron con un nivel de oxígeno > 85 % O2. Los grupos 2 y 4 recibieron inyecciones intraperitoneales de licopeno de 50 mg/kg/día; los otros grupos recibieron inyecciones intraperitoneales de aceite de maíz con el mismo volumen. Las ratas se sacrificaron en el día 11, después de 10 días con hiperoxia. Se extrajeron los cerebros, y se evaluaron los parámetros del sistema oxidativo. Resultados: Se detectaron lesiones cerebrales por hiperoxia en sustancia blanca, regiones corticales y tálamo. Aumentó la cantidad de células apoptóticas y disminuyó la cantidad de células PCNA positivas en los grupos 3 y 4, comparados con el grupo 1. No se observó una mejora significativa en la cantidad de células apoptóticas y células PCNA positivas en los grupos 3 y 4; además, aumentó la apoptosis. Conclusión: Se halló que el licopeno no mostró efectos terapéuticos para el daño cerebral en ratas recién nacidas. Además, se demostró que el licopeno podría causar efectos tóxicos.

Objectives. In addition to protecting cells against free radical harm thanks to its anti-oxidant nature, lycopene strengthens the bonds among cells and improves cell metabolism. This study focuses on analyzing therapeutic effects of lycopene in hyperoxia-induced neurodegenerative disorders in newborn rats. Methods. Term newborn rats were divided into four groups as the normoxia control group (group-1), normoxia+lycopene group (group-2), hyperoxia control group (group-3) and hyperoxia+lycopene group (group-4). Group-1 and group-2 were monitored in room air while the group-3 and group-4 were monitored at > 85% O2. The group-2 and group-4 were injected with lycopene intrapertioneally (i.p. ) at 50mg/kg/day while the other groups were injected with corn oil i.p. at the same volume. The rats we sacrificed on the 11th day following the 10-day hyperoxia. The brains were removed and oxidant system parameters were assessed. Results. Injury resulting from hyperoxia was detected in the white matter, cortical regions, and thalamus of the brains. It was observed that the number of apoptotic cells increased and the number of proliferating cell nuclear antigen (PCNA) positive cells decreased in the groups-3 and 4 compared to the group-1. No significant improvement in the number of apoptotic cells and PCNA positive cells was observed in the groups-3 and 4, and apoptosis increased as well. Conclusion. This study found that lycopene, did not show any therapeutic effects for brain damage treatment in newborn rats. In addition, this study demonstrated that lycopene might lead to toxic effects.

El pensamiento moral después del daño cerebral adquirido / Moral thought after acquired cerebral damage

Resumen Introducción: El pensamiento moral es una habilidad mental que permite a los seres humanos respetar las normativas sociales implícitas y explícitas. Un factor que puede alterar su funcionamiento es el daño cerebral adquirido, como suele suceder en sujetos que han sufrido una injuria encefálica a nivel frontal. Objetivo: Analizar la relación entre el proceso del pensamiento moral y el funcionamiento cerebral, a través de la descripción de casos que han sufrido un daño cerebral adquirido, con la finalidad de explicitar la situación que vive un individuo luego de presentar un daño cerebral y volverse incapaz de respetar las normas sociales. Desarrollo: Se expone la clínica de pacientes que han sufrido un daño cerebral a nivel frontal, como es el caso de Phineas Gage, NN y Elliot, en los cuales se observó que su estado posterior al evento traumático, se caracterizó por retroceder a estadios previos del pensamiento moral, a diferencia de pacientes como el clásico HM, quien presentó un daño cerebral en una estructura diferente a la frontal. Conclusiones: Se discute el análisis realizado en torno al papel que desempeña el lóbulo frontal en el proceso de respeto de las normas sociales, su influencia en la interacción humana y cómo puede verse afectado el pensamiento moral cuando existe un daño cerebral a este nivel.

Introduction: Moral thinking is a mental skill that allows respecting implicit and explicit social norms. One factor that can alter its functioning is acquired brain damage, as is the case of subjects who have suffered a brain injury at the frontal lobe. Aim: To analyze the relationship between the process of moral thinking and brain functioning, through the description of cases that have suffered acquired brain damage, with the purpose of explaining the situation that an individual lives after presenting brain damage and becoming unable to respect social norms. Development: The clinic of patients who have suffered brain damage at the frontal level, such as Phineas Gage, NN and Elliot, is shown, in which it was observed that its state after the traumatic event was characterized by going back to previous stages of thinking moral, unlike a subject who may present brain damage in later structures. Conclusions: We discuss the analysis performed on the role of the frontal lobe in the process of respecting social norms that allow human interaction and how it can be affected by brain damage.

Effect of four drug-loaded hydrogels on prevention of hypoxic brain damage / 国际药学研究杂志

Objective: To investigate the preventive effect of puerarin-,geonone(G20)-,timosaponin BⅡ- and cannabidio(l CBD)-loaded nasal hydrogels on the hypoxic brain injury in mice. Methods: The drug-loaded 4 hydrogels were prepared with poloxamer 407 and poloxamer 188. The healthy adult male SPF BALB/c mice were randomly divided into seven groups(n=5):the normal group,saline(NS)group,blank hydrogel group,puerarin hydrogel group,G20 hydrogel group,timosaponin BⅡhydrogel group and CBD hydrogel group. After 8 days of continuous nasal administration, the anti-hypoxia activity was assayed by the airtight hypoxia test at atmospheric pressure,by recording the survival time of the mice in the test conditions. Meanwhile,the peripheral blood cell counts,pathological changes in the mouse brain tissue and the expression of hypoxia inducible factor-1α(HIF-1α)in the cerebral hippocampal area were also examined. Results The G20 and CBD hydrogels could significantly prolong the survival time of mice in the airtight hypoxia test (P<0.01 and P<0.05),and the red blood cel(l P<0.01 and P<0.05)and hemoglobin counts(P<0.05 and P<0.05) in the mouse peripheral blood were significantly higher in the G20 and CBD hydrogel groups than those in the NS group, indicating that the G20 and CBD hydrogels could increase oxygen-carrying capacity of the peripheral blood in mice. The G20 and CBD hydrogels reduced inflammatory cells in the brain tissues of mice,and mice cell pyknosis and hyperchro- mism,suggesting that G20 and CBD could alleviate the brain injury caused by hypoxia. The immunohistochemistry analysis results for the brain tissue slides of mice showed that the HIF-1α expression in the cerebral hippocampal area in the G20 group was significantly decreased(P<0.01)to the similar level of the normal group. Conclusion: The G20 nasal hydro- gels showed a good anti-hypoxia effect to prevent hypoxic brain injury in the hermetic hypoxia mice model at atmospheric pressure. The mechanism was likely related to the improvement of antioxidant capacity of the body as well as the free radi- cal scavenging and nerve cell protecting effect of G20.

Effect of granulocyte-colony stimulating factor on endoplasmic reticulum stress in neonatal rats after hypoxic-ischemic brain damage / 中华实用儿科临床杂志

Objective@#To evaluate the protective effect of granulocyte-colony stimulating factor(G-CSF) on neonatal rats after hypoxic-ischemic brain damage(HIBD)and its effect on endoplasmic reticulum (ER) stress.@*Methods@#According to the random number table, a total of 54 Sprague-Dawley (SD) rats aged 7 days were divided into 3 groups(18 rats in each group): Sham group, HIBD group and G-CSF group, and the improved Rice method was used to establish a neonatal rat model of HIBD.A dose of 50 μg/kg of G-CSF was administered intraperitoneally 1 hour after HIBD (G-CSF group), while the rats in HIBD group and Sham group received saline only.At 24 hours of HIBD, pups were euthanized to quantify brain infarct volume by using 2, 3, 5-Triphenyltetrazolium chloride.Hematoxylin-Eosin (HE) staining was used to observe the changes of brain structure.Neuronal cell death was determined by using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Then the expressions of glucose-regulated protein 78 (GRP78), cysteinyl aspartate specific proteinase 12 (Caspase-12), CCAAT/enhancer binding-protein homologous protein (CHOP) were assessed by Western blot and immunofluorescence staining.@*Results@#Twenty-four hours after operation, HE staining showed that no significant neuronal damage was observed in Sham group.The brain tissue structure of rats in the HIBD group was significantly damaged, while some improvement was observed in the G-CSF group.The infarction volume in HIBD group[(25.40±5.15)%] increased compared with that in the Sham group[(0.31±0.15)%] and the G-CSF group[(16.36±4.97)%], and the differences were statistically significant(all P<0.05). There was increased positive expression of GRP78 protein in HIBD group, compared with that in the Sham group and the G-CSF group[(49.38±10.06)% vs.(9.12±4.50)%, (30.61±6.35)%], and the differences were statistically significant (all P<0.05). The percentage of apoptosis in the hippocampal CA1 region and conex in HIBD group [(44.84±11.54)%, (48.23±14.07)%] were higher than those in the G-CSF group [(17.87±7.20)%, (26.18±9.96)%], and the differences were statistically significant (all P<0.05). The expression of GRP78, CHOP and Caspase-12 in the HIBD group (0.63±0.24, 0.72±0.21, 0.68±0.25) were higher than those in the Sham group (0.20±0.08, 0.28±0.08, 0.23±0.07), and the G-CSF group (0.39±0.13, 0.51±0.18, 0.48±0.16), and the differences were statistically significant (all P<0.05).@*Conclusions@#G-CSF exerts neuroprotective effect on the neonatal rats after HIBD.G-CSF may be an effective treatment of HIBD by reducing ER stress-induced neuronal apoptosis.