摘要
SUMMARY: Stroke is the leading cause of acquired physical disability in adults and second leading cause of mortality throughout the world. Treatment strategies to curb the effects of stroke would be of great benefit. Pongamia pinnata is a recent attraction in medicine, owing to its abundant medicinal benefits with minimal side effects. The present study aimed to examine acute and subacute effect of Pongamia pinnata leaf extract on transient cerebral hypoperfusion and reperfusion (tCHR) in Wistar rats. 24 adult Wistar rats (12 each for acute and subacute study) were divided in to four groups each viz normal control group, tCHR + NS group, tCHR + 200mg/kg bw and tCHR + 400mg/kg bw groups. Cerebral ischemia induction was carried out by bilateral common carotid artery occlusion and reperfusion. Ethanolic extract of Pongamia pinnata leaves were orally administered for 7 days and 21 days after the surgical procedure for acute and subacute study respectively. Behavioural analysis, histological assessment, and estimation of mRNA levels of HIF-1, GDNF, BDNF and NF-kB were performed. In both acute and subacute study, there was significant improvement in the beam walking assay, neuronal count, decreased neuronal damage in histological sections and higher mRNA expression of BDNF and GDNF in the treatment groups. There was no significant difference in the expression of HIF1 and NF-kB. Thus, Pongamia pinnata has excellent neurorestorative property reversing many of the effects of ischemic stroke induced by tCHR in rats with the underlying mechanism being an improvement in the expression of neurotrophic factors GDNF and BDNF.
El ataque cerebrovascular es la principal causa de discapacidad física adquirida en adultos y la segunda causa de mortalidad en todo el mundo. Las estrategias de tratamiento para frenar los efectos del ataque cerebrovascular serían de gran beneficio. Pongamia pinnata es una atracción reciente en la medicina, debido a sus abundantes beneficios medicinales con mínimos efectos secundarios. El presente estudio tuvo como objetivo examinar el efecto agudo y subagudo del extracto de hoja de Pongamia pinnata sobre la hipoperfusión y reperfusión cerebral transitoria (tCHR) en ratas Wistar. Se dividieron 24 ratas Wistar adultas (12 cada una para el estudio agudo y subagudo) en cuatro grupos, el grupo control normal, el grupo tCHR + NS, los grupos tCHR + 200 mg/kg de peso corporal y tCHR + 400 mg/kg de peso corporal. La inducción de la isquemia cerebral se llevó a cabo mediante oclusión y reperfusión bilateral de la arteria carótida común. El extracto etanólico de hojas de Pongamia pinnata se administró por vía oral durante 7 días y 21 días después del procedimiento quirúrgico para estudio agudo y subagudo respectivamente. Se realizaron análisis de comportamiento, evaluación histológica y estimación de los niveles de ARNm de HIF-1, GDNF, BDNF y NF-kB. Tanto en el estudio agudo como en el subagudo, hubo una mejora significativa en el ensayo de desplazamiento del haz, el recuento neuronal, una disminución del daño neuronal en las secciones histológicas y una mayor expresión de ARNm de BDNF y GDNF en los grupos con tratamiento. No hubo diferencias significativas en la expresión de HIF1 y NF-kB. Por lo tanto, Pongamia pinnata tiene una excelente propiedad neurorestauradora que revierte muchos de los efectos del ataque cerebrovascular isquémico inducido por tCHR en ratas, siendo el mecanismo subyacente una mejora en la expresión de los factores neurotróficos GDNF y BDNF.
Subject(s)
Animals , Rats , Plant Extracts/administration & dosage , Stroke/drug therapy , Millettia/chemistry , Plant Extracts/pharmacology , Cerebral Cortex/drug effects , Brain Ischemia/drug therapy , Administration, Oral , NF-kappa B , Rats, Wistar , Brain-Derived Neurotrophic Factor/genetics , Disease Models, Animal , Hypoxia-Inducible Factor 1/genetics , Glial Cell Line-Derived Neurotrophic Factor/genetics , Real-Time Polymerase Chain Reaction , Nerve Growth Factors/administration & dosage摘要
Objective:To evaluate the effect of propofol on parvalbumin (PV) neurons in the medical prefrontal cortex(mPFC)of rats with social behavior disorders induced by chronic sleep deprivation.Methods:Forty-two SPF male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 3 groups ( n=14 each) using a random number table method: control group (group Con), chronic sleep deprivation plus natural sleep group (group CSD+ NS), and chronic sleep deprivation plus propofol group (group CSD+ Pro). Sleep deprivation model was established by the modified multiple platform method, the rats were placed in the sleep-deprivation tank for 20 h a day (14: 00-10: 00), and allowed to sleep naturally for 4 h (10: 00-14: 00) a day for 28 consecutive days. Propofol 40 mg/kg was intraperitoneally injected for 28 consecutive days after sleep deprivation in CSD+ Pro group. While the equal volume of 10% fat emulsion was given in Con and CSD+ NS groups. After the end of sleep deprivation, a three-box social experiment was used to detect the social behavior of rats, and the number of the PV positive cells and density of the perineuronal network (PNN) in the mPFC area were measured by immunofluorescence. Results:Compared with group Con, the pertentage of rapid eye movement sleep and sniffing time preference coefficients for the strange rat 1 in the first stage and for the strange rat 2 in the second stage were significantly decreased, and the number of the PV positive cells and density of PNN in the mPFC area were decreased in group CSD+ NS ( P<0.05). Compared with group CSD+ NS, the sniffing time preference coefficients for the strange rat 1 in the first stage and for the strange rat 2 in the second stage were significantly increased, the number of the PV positive cells and density of PNN in the mPFC area were increased( P<0.05), and no significant change was found in the percentage of the rapid eye movement sleep in group CSD+ Pro. Conclusions:Propofol probably increases the number and function of PV neurons in the mPFC and ameliorates sleep deprivation-induced social behavior disorders in sleep-deprived rats.
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Objective @#To explore and optimize the in vitro primary culture method of astrocytes in neonatal mouse cerebral cortex , which provides a better solution for the in vitro culture of astrocytes.@*Methods @#In order to optimize the in vitro culture method of mouse cerebral cortex astrocytes , 3 ⁃day⁃old C57BL/6J mouse cerebral cortex tissues were taken , meninges and blood vessels were removed , digested by pancreatic enzymes and centrifuged , andhigh⁃glucose dulbecco ′s modified eagle medium (DMEM) was added to form cell suspension , which was purified by differential adhesion method , cross hand method and constant temperature shaking method.The cells were inoculated in poly⁃D ⁃lysine⁃coated culture bottles with different culture densities , and the purity of astrocytes was determined by morphological ob servation and immunofluorescence staining.@*Results @#The cells were inoculated at a density of 5 × 106 cells per bottle with good effect and high activity. The purity of astrocytes reached 99% by using high sugar DMEM medium combined with differential adhesion method , cross hand method and constant temperature shaking method.@*Conclusion @#The primary culture method of astrocytes in mouse cerebral cortex is successfully established and optimized.
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Objective To investigate the mechanism of icariin regulating the NLRP3 inflammasome in the treatment of cerebral ischemia-reperfusion injury in rats.Methods A rat model of focal cerebral ischemia-reperfusion was induced using the thread embolism method.At 24 hours post-operation,the rats were randomly allocated into a sham operation group,model group,butylphthalide group(70 mg/kg),ICA-low dose(20 mg/kg),ICA-middle dose(40 mg/kg),and ICA-high dose(80 mg/kg)groups.The corresponding drugs were administered by gavage at 10 mL/kg once a day for 13 consecutive days.One hour after the last administration,neurological function was scored.The cerebral cortex was observed by hematoxylin-eosin(HE)staining.Expression of interleukin(IL)-1β and IL-18 in the cerebral cortex was determined by immunohistochemistry.Expression of NLRP3,ASC,and Caspase-1 in the cerebral cortex was determined by Western Blot.Results In contrast to the sham operation group,there was a notable increase in neural function scores within the model group.The ischemic area around the visible cerebral cortex showed neuron necrosis at various level or glial cell proliferation,and the number of intact neurons was significantly reduced.IL-1β and IL-18 positive cells were significantly increased.Expression of NLRP3,ASC,and Caspase-1 was significantly increased(P＜0.01,P＜0.05).After treatment with icariin,the neural function score was decreased significantly.The degree of neuronal necrosis in the peri-ischemic area was significantly reduced,and the number of intact neurons was significantly increased.IL-1 β and IL-18-positive cells were decreased significantly.Expressions of NLRP3,ASC,and Caspase-1 were significantly decreased(P＜0.01,P＜0.05).Conclusions Treatment of cerebral ischemia-reperfusion injury by icariin may be related to regulation of the NLRP3 inflammasome.
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ObjectiveTo explore the cerebral cortex activation in different swallowing periods using functional near-infrared spectroscopy (fNIRS). MethodsFrom October to December 2023, a total of 18 healthy adults were recruited to perform four tasks of visual stimulation, chewing, tongue tip sliding and repeated swallowing during fNIRS acquisition, to calculate the cortical activation β values covering a total of 41 channels in frontal, parietal and occipital lobes. ResultsDuring the preoral period, the bilateral pre-motor and supplementary motor cortex (PSMC), bilateral inferior prefrontal gyrus, right visual association cortex (AVC), and left primary motor cortex (PMC) were significantly activated (P < 0.05). During oral preparation, the right pars triangularis (PTG), right frontal polar area (FPA), right dorsolateral prefrontal cortex (DPC), left primary somatosensory cortex (PSC), left PSMC and left PMC were significantly activated (P < 0.05). During the transition between oral and pharyngeal phases, bilateral PSMC and bilateral PMC were significantly activated (P < 0.05). Bilateral PSC, bilateral PTG, bilateral FPA, bilateral orbitofrontal area, bilateral PSMC, bilateral DPC and bilateral PMC were significantly activated during two consecutive periods of oral and pharyngeal phases (P < 0.05). ConclusionThe swallowing movement requires the coordination of the frontal, parietal and occipital cortex. The main activated brain areas are different in different swallowing stages, and the PSMC and PMC are involved in most swallowing stages.
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ABSTRACT Purpose: Amid rising health awareness, natural products which has milder effects than medical drugs are becoming popular. However, only few systems can quantitatively assess their impact on living organisms. Therefore, we developed a deep-learning system to automate the counting of cells in a gerbil model, aiming to assess a natural product's effectiveness against ischemia. Methods: The image acquired from paraffin blocks containing gerbil brains was analyzed by a deep-learning model (fine-tuned Detectron2). Results: The counting system achieved a 79%-positive predictive value and 85%-sensitivity when visual judgment by an expert was used as ground truth. Conclusions: Our system evaluated hydrogen water's potential against ischemia and found it potentially useful, which is consistent with expert assessment. Due to natural product's milder effects, large data sets are needed for evaluation, making manual measurement labor-intensive. Hence, our system offers a promising new approach for evaluating natural products.
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Fundamento: El cerebro durante la etapa prenatal es uno de los órganos más afectados por factores teratógenos, por ejemplo la Diabetes Mellitus Pregestacional. Su efecto sobre este en esta etapa requiere un mayor conocimiento porque es un importante predictor de problemas cognitivos y psicológicos en la edad adulta. Para el estudio de la corteza cerebral resultan muy útiles los modelos animales, combinados con técnicas morfométricas tendremos una mayor precisión a la hora de establecer las causas que condicionan el daño. Objetivo: Determinar las posibles diferencias de los indicadores morfométricos nucleares: área, volumen, y factor de forma en las neuronas de la corteza cerebral temporal de gazapos de ratas Wistar normal y en un modelo animal con diabetes mellitus pregestacional. Métodos: Se realizó un estudio experimental básico con 16 cerebros de gazapos de ratas Wistar en el período comprendido entre junio 2021 a junio 2022 en la Universidad de Ciencias Médicas de Holguín. Dichos cerebros se organizaron en dos grupos de ocho cada uno. Un grupo control con los procedentes de gazapos de ratas sanas y un grupo casos con los cerebros de gazapos de ratas diabéticas. Se estudiaron indicadores morfométricos nucleares como el área, el volumen y el factor de forma. Resultados: El área y el volumen nuclear muestran valores superiores en el grupo control .El valor del factor de forma no mostró diferencias. Conclusiones: Los resultados obtenidos traducen que la Diabetes Mellitus Pregestacional puede causar daño a las neuronas del tejido nervioso de la zona cerebral estudiada.
Background: The brain during the prenatal stage is one of the organs most affected by teratogenic factors such as Pregestacional Diabetes Mellitus. Its effect on it during these stages requires greater knowledge because it is an important predictor of cognitive and psychological problem in age adult. For the study of the cerebral cortex, animal models are very useful, combined with morphometric techniques, greater precision will be obtained when establishing the causes to determinate the damage. Objective: To determine the possible differences of the nuclear morphometric indicators: area, volume and shape factor in the neurons of the temporal cerebral cortex of normal Wistar rat kits and in an animal model with pregestacional diabetes mellitus. Method: A basic experimental study was carried out with 16 brains of Wistar rats in the period from June 2021 to June 2022 at the University of Medical Sciences of Holguín. These brains were organized into two groups of eight each. A control group with those from healthy rat kits and a case group with brain from diabetic rats kits. Nuclear morphometric indicators such as area, volume and shape of factor were studied. Results: The area and the nuclear volume show superior values in the control group. The value of the shape factor did not show significant difference. Conclusions: the results obtained show that Pregestational Diabetes Mellitus can cause damage to the neurons of the nervous tissue of the brain area studied.
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Resumen Antecedentes: La aparición temprana de serotonina en el cerebro fetal y sus efectos en la morfogénesis cerebral apoyan su papel neurotrófico. Objetivo: Determinar la presencia de células serotoninérgicas y la expresión de triptófano-5-hidroxilasa (TPH), 5-hidroxitriptamina (5-HT), transportador de serotonina (SERT), receptor 5-HT1A y Pet-1 durante el desarrollo de la corteza cerebral, tanto in situ como en cultivo de tejidos. Material y métodos: Se realizó estudio observacional descriptivo en ratas Wistar preñadas. La presencia del tapón se consideró el inicio de la gestación; en los días 13, 16 y 17 se practicaron cesáreas para obtener los fetos e inmediatamente se disecaron los cerebros para identificar células serotoninérgicas, TPH, 5-HT, SERT, 5-HT1A y Pet-1 en cultivo de tejido e in situ mediante inmunomarcaje detectado en un microscopio confocal. Resultados: Células y terminales serotoninérgicas fueron observadas en el mesencéfalo el día 17 de gestación y en cocultivos de neopalio los días 13 y 16. También se observaron células inmunopositivas a TPH, 5-HT, SERT y Pet-1 en el neopalio en el día 12 del cultivo. Conclusiones: Se confirmó la presencia de células serotoninérgicas y otros elementos del sistema serotoninérgico en la corteza cerebral temprana, la cual puede ser transitoria y participar en los procesos de maduración cortical durante el desarrollo cerebral.
Abstract Background: Early appearance of serotonin in the fetal brain and its effects on brain morphogenesis support its neurotrophic role. Objective: To determine the presence of serotonergic cells and the expression of tryptophan-5-hydroxylase (TPH), 5-hydroxytryptamine (5-HT), serotonin transporter (SERT), 5-HT1A receptor and Pet-1 during the development of the cerebral cortex, both in situ and in tissue cultures. Material and methods: A descriptive, observational study was carried out in pregnant Wistar rats. The presence of the plug was regarded as the beginning of gestation. On days 13, 16 and 17, cesarean sections were performed to obtain the fetuses, and the brains were then immediately dissected to identify the presence of serotonergic cells, TPH, 5-HT, SERT, 5-HT1A and Pet-1 in tissue cultures and in situ by immunostaining detected on a confocal microscope. Results: Serotonergic cells and terminals were observed in the midbrain on day 17 of gestation, and in neopallium cocultures on days 13 and 16. TPH, 5-HT, SERT and Pet-1 immunopositive cells were also observed in the neopallium on day 12 of culture. Conclusions: The presence of serotonergic cells and other elements of the serotonergic system in the early cerebral cortex was confirmed, which may be transient and participate in cortical maturation processes during brain development.
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Introducción: la necrosis laminar cortical es un término radiológico que describe la presencia de lesiones hiperdensas de localización cerebral, las cuales siguen una distribución giriforme y se observan con mayor sensibilidad en los estudios de resonancia magnética cerebral (RM). Esta condición patológica, que afecta a la corteza del cerebro, suele ser secundaria a una depleción de sus fuentes energéticas como consecuencia de hipoxia cerebral, alteraciones metabólicas, hipoglicemia, falla renal o hepática, intoxicaciones o infecciones. Presentación del caso: se reporta el caso de un hombre de 23 años, con antecedente de consumo crónico de alcohol, quien ingresó al servicio de urgencias de nuestra institución con un estado epiléptico. El estudio de resonancia magnética cerebral demostró la presencia de una necrosis laminar cortical con posterior déficit neurocognitivo y funcional. Conclusión: si se consideran las secuelas neurológicas potenciales asociadas a un estado epiléptico, relacionadas con necrosis laminar cortical cerebral, es necesario hacer un diagnóstico etiológico precoz, así como una atención terapéutica temprana a los pacientes.
Introduction: Cortical laminar necrosis (CLN) is radiologically defined as high-intensity cortical lesions on T1-weighted MRI images that follow a gyral distribution in the brain. Histopathologically, this pathological condition is characterized by necrosis of the cortex involving neurons, glial cells, and blood vessels. It is usually triggered by hypoxia, metabolic alterations, drugs, intoxications, or infections. Case description: We report the case of a 23-year-old man with a history of chronic alcohol abuse who was admitted to our institution with status epilepticus. The brain magnetic resonance imaging performed on this patient showed cortical laminar necrosis associated with subsequent neurocognitive deficits. Conclusion: Due to the potential neurological sequelae secondary to status epilepticus in relation to cortical laminar necrosis as permanent brain damage, it is necessary to provide early diagnosis and treatment for these patients.
Subject(s)
Status Epilepticus , Hypoxia, Brain , Cerebral Cortex , Neuroimaging摘要
Objective:To investigate the effect of insular involvement on the outcomes of patients with acute anterior circulation ischemic stroke.Methods:Patients with acute anterior circulation ischemic stroke admitted to the Department of Neurology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2015 to December 2020 were retrospectively included. Demographic data, vascular risk factors, clinical and laboratory data, as well as treatment and outcomes were collected. Firstly, the correlation between the insular involvement and the outcomes was investigated, and then the bootstrap method was used to clarify the mediating role of infarct volume between the insular involvement and the poor outcomes.Results:A total of 450 patients with acute anterior circulation ischemic stroke were enrolled, among whom 79 cases (17.6%) had insular involvement and 41 (9.1%) had left insular involvement. There were 111 (24.7%) with poor outcomes, including 5 (1.1%) died. Compared to the non-insular involvement group, the insular involvement group had a higher proportion of patients with atrial fibrillation, shorter onset to door time, higher neutrophil-to-lymphocyte ratio (NLR), higher National Institutes of Health Stroke Scale (NIHSS) score at admission, larger infarct volume, and higher proportion of patients with poor outcomes (all P<0.05). In addition, patients with left insular involvement were younger than those with right insular involvement, had a higher baseline NIHSS score, a lower proportion of patients with minor stroke (NIHSS score ≤8), and had a longer onset to door time (all P<0.05). Compared to the good outcome group, the poor outcome group was older, with a higher proportion of female patients, higher systolic blood pressure, blood glucose, NLR, and NIHSS scores at admission, larger infarct volume, and a higher proportion of patients with insular involvement (all P<0.05). Mediation analysis suggested that the mediating effect of infarct volume between the insular involvement and the poor outcomes was significant (95% confidence interval 0.033-0.230; P=0.008). Conclusions:insular involvement in patients with acute anterior circulation ischemic stroke is associated with the poor outcomes, and this association may be mediated by infarct volume. Patients with left insular involvement may have more severe symptoms than those with right insular involvement, but there is no significant difference in the outcomes.
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Objective:To investigate the significance of abnormal morphology of Sylvian fissure detected by fetal neurosonogram (NSG) in prenatal diagnosis of malformations of cortical development (MCD).Methods:This retrospective study involved fetuses with abnormal morphology of Sylvian fissure on prenatal NSG in Peking University First Hospital between January 2016 and December 2021. Clinical data including the basic information as well as the results of NSG, genetic examinations and MRI were collected. The diagnosis of MCD could be made when both brain morphological abnormalities and pathogenic/likely pathogenic genetic abnormalities were presented. The association between the abnormal morphology of Sylvian fissure and MCD was analyzed by descriptive analysis.Results:Thirteen participants who had complete genetic information were included in this study [defined as those who were found with pathogenic/likely pathogenic copy number variation (CNV) or those who further underwent whole-exome sequencing (WES) as no pathogenic/likely pathogenic CNV were detected]. Twelve fetuses (12/13) were eventually diagnosed with MCD. Pathogenic CNV were found in seven fetuses and pathogenic point mutations in five, involving six pathogenic genes and four genetic syndromes. Symmetric morphologic abnormality of Sylvian fissure was detected in 10 cases by prenatal NSG with shallow and broad shape in six and abnormal angle of Sylvian fissure in four. The other two fetuses showed asymmetric abnormal morphology of Sylvian fissure that was shallow and broad shape on one side and abnormal angle on the other. The imaging features of MCD present by prenatal NSG and were consistent with those of MRI.Conclusions:Abnormal morphology of Sylvian fissure detected by prenatal NSG is important in MCD diagnosis. Genetic examination are recommended to the fetuses with abnormal morphology of Sylvian fissure. For those requiring for genetic analysis, chromosomal microarray analysis together with WES might be an optimal choice.
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Objective:To explore the effect of desflurane on activity of neurons in 2/3 layer cortex of mice by using high-resolution light-field intelligent imaging system.Methods:Six SPF healthy male Rasgrf/Ai148d mice, aged 8-12 weeks, weighing 25-30 g, were selected. The 6 mice were subjected to skull replacement surgery and then recovered for 2 weeks before experiment.The mice were first fixed under the high-resolution light-field intelligent imaging system for 5 min before calcium signals in 2/3 layer cortex were recorded. The 7.5% desflurane was inhaled for anesthesia starting from 100 s of recording and inhalation was stopped at 700 s, and then the recording continued for 700 s. The total duration of the experiment was 1 500 s. Neurons were extracted and data were analyzed using MATLAB software.Results:When mice were subjected to inhalation anesthesia with desflurane, the calcium fluorescence intensity and percentage of active neurons in the cortex 2/3 layers initially increased significantly, then continuously declined, stabilizing after about 100 s of inhalation. After cessation of inhalation, it gradually recovered to the pre-anesthetic level around 50 s post-inhalation. During the induction period of anesthesia, the percentage of active neurons was significantly higher in the retrosplenial cortex than in the other brain regions ( P<0.05). Conclusions:The disappearance and recovery of consciousness induced by desflurane anesthesia at the neuronal level is not a " symmetrical" process. Neuronal activity in the brain exhibits asymmetry when entering and recovering from an anesthetized state. The retrosplenial cortex, which is related to sleep-wake cycles, may play a crucial role in maintaining consciousness during induction of anesthesia with desflurane.
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ObjectiveTo study the effect of upper limb robot-assisted therapy on upper limb function and cerebral cortex activation in stroke patients using functional near-infrared spectroscopy (fNIRS). MethodsFrom January, 2022 to January, 2023, 32 stroke patients in Zhejiang Rehabilitation Medical Center were randomly divided into control group (n = 16) and experimental group (n = 16). Both groups received routine neurological medication and routine rehabilitation. The control group received routine upper limb exercises, the experimental group received upper limb robot-assisted therapy. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and fNIRS (oxyhemoglobin, deoxyhemoglobin, and total hemoglobin) before and four weeks after treatment. NIRS_SPM was used for activation analysis, Homer2 was used for blood oxygen concentration analysis. ResultsAfter treatment, the score of FMA-UE increased in both groups (|t| > 5.910, P < 0.001), and was higher in the experimental group than in the control group (t = -2.348, P < 0.05). fNIRS activation results showed that, the activation increased in the experimental group after treatment in channel 17 (F = 9.354, P < 0.01), and it was more than that in the control group (F = 5.217, P < 0.05). fNIRS blood oxygen concentration results showed that, the blood oxygen concentration increased in the experimental group after treatment in channel 17 (F = 12.179, P < 0.01), and it was more than that in the control group (F = 4.883, P < 0.05). ConclusionThe upper limb robot-assisted therapy can improve the upper limb motor function and cerebral cortex activation of stroke patients.
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ObjectiveTo investigate the effect of Astragalin （AST） on apoptosis of cerebral cortex neurons in APP/PS1 transgenic mice. MethodsEighteen six-month-old male APP/PS1 transgenic mice were randomly divided into APP/PS1 group， APP/PS1+ 40 mg/kg AST group and APP/PS1+ 20 mg/kg Donepezil （DNP） group， with six mice in each group. At the same time， six male C57BL/6 mice were selected as the normal control group. After intraperitoneal injection of AST once a day and continuous administration for one month， we used Tunel staining to detect the apoptosis of neurons in the cerebral cortex of APP/PS1 mice； immunofluorescent staining to examine the expression of apoptosis-related proteins Bax， Bcl-2， Caspase9 and Cleaved-Caspase3 in the cerebral cortex neurons of APP/PS1 mice； Western blot method to evaluate the changes of the expression of Bax， Bcl-2， Caspase9 and Caspase3. ResultsTunel staining showed that 40 mg/kg AST and 20 mg/kg DNP both reduced the apoptosis of neurons in the cerebral cortex of APP/PS1 mice， AST with more significant inhibition effect. Immunofluorescent staining revealed that 40 mg/kg AST and 20 mg/kg DNP both inhibited the expression of Bax， Caspase9， and Cleaved-Caspase3， and icreased the expression of Bcl-2 in the cerebral cortex neurons of APP/PS1 mice. Western blot results further confirmed that 40 mg/kg AST and 20 mg/kg DNP both down-regulated the expression of Bax （P < 0.05， P < 0.05）， Caspase9 （P < 0.005， P < 0.05） and Caspase3 （P < 0.0001， P < 0.0001） ， and up-regulated the expresstion of Bcl-2 （P < 0.05， P < 0.05） in the cerebral cortex neurons of APP/PS1 mice. ConclusionsAST can inhibit the apoptosis of cerebral cortex neurons in APP/PS1 mice.
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Objective To understand the characteristics and developmental differences between cerebral organoids in vitro and normal cerebral cortices in vivo. Methods 1. Grouping: cerebral cortices in vivo group and cultured cerebral organoids in vitro group. 2. Sample collection: cortical tissues were collected from Kunming mouse embryos at embryonic day 7.5(E7.5), E9.5, E11.5, E14.5, and postnatal day 3 (P3) or P7. Three specimens were taken from each group. Meanwhile, cerebral organoids were cultured with mouse induced pluripotent stem cells (iPSCs), and samples at different culture time point were collected, and more than 3 samples were collected at each time point. 3. Detection method: the distribution of different types of cells in each group of specimens was analyzed by immunofluorescent staining. Results While relative similarities between in vivo cerebral cortical development and the cerebral organoids in vitro were observed, including the histogenesis, and the morphological differentiation of nerve cells and glial cells, the lamellar architecture of cerebral cortex in mouse brain was not observed in cerebral organoids. Conclusion The development of cerebral organoids in vitro has some similarity with body's cortical development. Therefore, cerebral organoids can be used to a substitution of cortex and diseases' models, but improvement of the existing technologies is necessary.
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Objective To observe and analyze functional areas of the cerebral cortex in C57BL/6 mice of various ages.Methods Improved alkaline phosphatase staining was used to reveal the microvascular morphology of the cerebral cortex in C57BL/6 mice,including the motor cortex(primary and secondary motor cortex),sensory cortex(primary and secondary somatosensory cortex),visual cortex(primary and secondary visual cortex),and auditory cortex(primary and secondary auditory cortex),olfactory cortex(extrarhinal and entorhinal cortex).Images were captured under an OLYMPUS BX51 microscope with Image-Pro Plus 5.1 software.The microvascular length density(Lv),microvascular surface area density(Sv),and microvascular volume density(Vv)were analyzed by Image-Pro Plus 5.1 software.Results Expression of alkaline phosphatase was abundant in cerebral cortical microvessels of adult and elderly mice,and slightly expressed in juvenile mice,but not in lactating mice.Pial blood vessels enter the cortex in T shape,Y shape,large arc,and small arc four manners.Lv,Sv and Vv in different parts of the same aged mice showed a decreasing trend in motor,sensory,visual,auditory and olfactory cortexes,and the microvascular density of Lv,Sv and Vv in motor and sensory cortexes was statistically significant compared with the olfactory cortex(P<0.05).The vascular density in all functional areas in elderly mice was lower than that in adult mice,but no statistical significance was found(P>0.05).Conclusions The expression of alkaline phosphatase in microvessels in functional areas of the cerebral cortex in C57BL/6 mice increases with age and reached its peak value in adulthood.The microvascular architecture in the brain provides morphological parameters to establish cerebrovascular disease models.
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Objective@#To investigate the potential relationship between sensory characteristics and gray matter volumes in children with autism spectrum disorders (ASD), to provide a basis for the diagnosis and treatment of children with ASD.@*Methods@#A total of 40 ASD children who were treated or recovered in Xi an medical institutions and 16 typically developing (TD) children who were from several kindergatens in Xi an were invited for participation. Sensory characteristics were evaluated by the sensory processing and self regulation checklist, 3D structural brain images were obtained with TIWI, and gray matter volumes were analyzed by voxel based morphometry. Sensory characteristics and gray matter volumes were compared between groups and the relationship between sensory characteristics and different gray matter volumes were analyzed.@*Results@#The scores of auditory, visual, tactile, sensory processing ability and sensory under responsivity in the ASD group were lower than those in the TD group ( Z/t =-2.63, -2.57 , -3.11, -2.19, -3.83, P <0.05). Gray matter volumes in nine brain regions increased in the ASD group compared to the TD group, including the left and right posterior inferior lobe, right parahippocamal gyrus, left insula, left media frontal gyrus, left superion occipital gyrus, right superion occipital gyrus, right superion parietal lobe, and right posterion central gyrus ( t =3.53, 3.69 , 3.37, 3.86, 3.61, 3.37, 4.04, 3.38, 3.16, P <0.01). In the ASD group, the scores of visual, vestibular, proprioceptive, sensory processing ability, sensory seeking behavior and sensory over responsivity were negatively correlated with gray matter volumes of left superior occipital gyrus ( r =-0.36, -0.40, -0.39, -0.36, -0.40, -0.36), and the scores of visual, vestibular, and sensory over responsivity were negatively correlated with gray matter volumes of the right superior parietal lobule ( r =-0.36, -0.50, -0.42)( P <0.05).@*Conclusion@#The presence of paresthesia in children with ASD is associated with gray matter volumes of the left superior occipital gyrus and right superior parietal lobule.
摘要
Abstract Objective: To assess the reliability of phase-sensitive inversion recovery (PSIR) magnetic resonance imaging (MRI) and its accuracy for determining the topography of demyelinating cortical lesions in patients with multiple sclerosis (MS). Materials and Methods: This was a cross-sectional study conducted at a tertiary referral center for MS and other demyelinating disorders. We assessed the agreement among three raters for the detection and topographic classification of cortical lesions on fluid-attenuated inversion recovery (FLAIR) and PSIR sequences in patients with MS. Results: We recruited 71 patients with MS. The PSIR sequences detected 50% more lesions than did the FLAIR sequences. For detecting cortical lesions, the level of interrater agreement was satisfactory, with a mean free-response kappa (κFR) coefficient of 0.60, whereas the mean κFR for the topographic reclassification of the lesions was 0.57. On PSIR sequences, the raters reclassified 366 lesions (20% of the lesions detected on FLAIR sequences), with excellent interrater agreement. There was a significant correlation between the total number of lesions detected on PSIR sequences and the Expanded Disability Status Scale score (ρ = 0.35; p < 0.001). Conclusion: It seems that PSIR sequences perform better than do FLAIR sequences, with clinically satisfactory interrater agreement, for the detection and topographic classification of cortical lesions. In our sample of patients with MS, the PSIR MRI findings were significantly associated with the disability status, which could influence decisions regarding the treatment of such patients.
Resumo Objetivo: Avaliar a confiabilidade da sequência PSIR e sua precisão no diagnóstico topográfico de lesões corticais desmielinizantes em pacientes com esclerose múltipla (EM). Materiais e Métodos: Estudo transversal realizado em centro de referência terciário para EM e distúrbios desmielinizantes. Avaliamos a concordância entre três avaliadores na identificação e classificação topográfica de lesões corticais na ressonância magnética de pacientes com EM, utilizando as sequências FLAIR e PSIR. Resultados: Foram incluídos 71 pacientes com EM. Em PSIR detectou-se 1,5× mais lesões do que em FLAIR, com concordância satisfatória entre examinadores na identificação de lesões corticais, com coeficiente kappa de resposta livre (κFR) = 0,60, e na reclassificação topográfica das lesões, com κFR médio = 0,57. Os avaliadores reclassificaram 366 lesões em PSIR (20% das lesões detectadas em FLAIR), com excelente concordância. Houve correlação significativa do total de lesões detectadas em PSIR e o escore da escala de incapacidade EDSS (ρ = 0,35; p < 0,001). Conclusão: PSIR mostrou-se superior na detecção de lesões corticais e na classificação topográfica destas em comparação ao FLAIR, com concordâncias entre examinadores clinicamente satisfatórias. A associação significativa entre o número de lesões corticais em PSIR e o grau de incapacidade dos pacientes pode influenciar em decisões terapêuticas.
摘要
Resumen: La definición de consciencia en sí encierra una gran dificultad por su esencia y la inmensa complejidad de los numerosos componentes y procesos que la conforman. La consciencia como característica inherente al ser humano ha sido objeto de numerosos estudios y tratados, no sólo científicos, sino además filosóficos, religiosos, éticos, etcétera. Esto también incluye la diferencia entre consciencia y conciencia. La dificultad para poder establecer el principio que da origen a la consciencia, representa, por lo tanto, un gran reto para poder dilucidar con certeza lo que sucede con ésta durante el evento anestésico. Gracias al entendimiento que se va logrando a través de las investigaciones concernientes a las funciones de diferentes y complejas estructuras, tales como la substancia activadora reticular ascendente, el tálamo, partes del cuerpo estriado y la corteza cerebral, entre otras, que se relacionan gracias a la existencia de redes neuronales, integradas a su vez por nodos con funciones específicas y a la vez variadas, capaces de intercomunicar estas estructuras encefálicas, aun estando distantes, se tiene ahora nociones sólidas de dónde, cómo y cuánto se puede ver afectada la integración de la consciencia como consecuencia del efecto de los diferentes anestésicos.
Abstract: To define consciousness per se, involves a great difficulty because of its essence and the huge complexity regarding the great number of its components and the processes within. Consciousness, as a human characteristic, has been matter of large researching not only through a scientific approach, but also from the perspective of philosophic, religious, ethics investigations among others, including the distinction between consciousness and awareness. The trouble to define the foundation of consciousness implies a great challenge to get to know, what is happening during the anesthesia period. Through the understanding that has been accomplished by way of investigations concerning the different and complex functions of diverse neural structures such as the brain stem reticular formation, the thalamus, some parts of the striatum and the cerebral cortex among others, how they become connected by the neuronal nets who are compounded by nodes that have not only specific but a wide array of functions, capable of interconnect all these encephalic structures, even though they are far away, we know now with a good amount of certainty, where, how and how much the integrity of consciousness can be affected as a consequence of the different anesthetics effect.
摘要
Human cortical radial glial cells are primary neural stem cells that give rise to cortical glutaminergic projection pyramidal neurons, glial cells (oligodendrocytes and astrocytes) and olfactory bulb GABAergic interneurons. One of prominent features of the human cortex is enriched with glial cells, but there are major gaps in understanding how these glial cells are generated. Herein, by integrating analysis of published human cortical single-cell RNA-Seq datasets with our immunohistochemistical analyses, we show that around gestational week 18, EGFR-expressing human cortical truncated radial glial cells (tRGs) give rise to basal multipotent intermediate progenitors (bMIPCs) that express EGFR, ASCL1, OLIG2 and OLIG1. These bMIPCs undergo several rounds of mitosis and generate cortical oligodendrocytes, astrocytes and olfactory bulb interneurons. We also characterized molecular features of the cortical tRG. Integration of our findings suggests a general picture of the lineage progression of cortical radial glial cells, a fundamental process of the developing human cerebral cortex.